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Publication
1
Informed consent in the Women's Health Initiative Clinical Trial and Observational StudyAnne McTiernan
McTiernan A, Rossouw J, Manson J, Franzi C, Taylor V, Carleton R, Johnson S, Nevitt M. Informed consent in the Women's Health Initiative Clinical Trial and Observational Study. J Womens Health. 1995;4:519-29
none providedBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms1.pdf
The Women's Health Initiative (WHI) is one of the largest and most complex disease prevention studies ever conducted. Educating prospective participants about the study and obtaining informed consent is a sequential, multicomponent process, consisting of verbal and written information, a video, and the reading and witnessed signing of the informed consent forms. All informed consent materials were reviewed by study investigators, local Institutional Review Boards; the WHI Data and Safety Monitoring Board; the Women's Health Initiative Policy Advisory Committee; the National Institutes of Health; the Institute of Medicine in Washington, D.C.; focus groups of postmenopausal women; and the media. The consent process continues to be dynamic; as more is known about potential risks and benefits associated with participating in the WHI, the consent process has and will be revised accordingly.
Publication
4
The Women's Health Initiative: Overview of the nutrition componentsLesley Tinker
Tinker LF, Burrows ER, Henry H, Patterson R, Rupp J, Van Horn L. The Women's Health Initiative: Overview of the nutrition components. In: Krummel DA, Kris-Etherton PM, eds. Nutrition and women's health. Gaithersburg, MD: Aspen Publishers,1996:510-42
none providedBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms4.pdf
Publication
5
Women's Health Initiative: Why now? What is it? What's new?Karen Matthews
Matthews KA, Shumaker SA, Bowen DJ, Langer RD, Hunt JR, Kaplan RM, Klesges RC, Ritenbaugh C. Women's Health Initiative. Why now? What is it? What's new? Am Psychol. 1997 Feb;52(2):101-16
none providedBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/9104085https://www.whi.org/researchers/bibliography/Manuscripts/ms5.pdf
Studies collectively named the Women's Health Initiative (WHI) are currently enrolling 164,500 postmenopausal women in several overlapping clinical trials and an observational study. The overall goals of WHI are to understand the determinants of postmenopausal women's health and to evaluate the efficacy of practical interventions in preventing the major causes of morbidity and mortality in older women. This article reviews the research leading to the WHI studies; describes the study designs and protocols, with an emphasis on what's new about WHI from a psychological perspective; and outlines the major psychosocial hypotheses under investigation and the major challenges WHI presents to psychological science.
Publication
6
Low-fat diet practices of older women: Prevalence and implications for dietary assessmentRuth Patterson
Patterson RE, Kristal AR, Coates RJ, Tylavsky FA, Ritenbaugh C, Van Horn L, Caggiula AW, Snetselaar L. Low-fat diet practices of older women: Prevalence and implications for dietary assessment. J Am Diet Assoc. 1996 Jul;96(7):670-9
none providedBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/8675910https://www.whi.org/researchers/bibliography/Manuscripts/ms6.pdf
To evaluate the importance of information on low-fat diet practices and consumption of reduced-fat foods for accurate assessment of energy and fat intakes using a semiquantitative food frequency questionnaire (FFQ).Subjects were 7,419 women, aged 50 to 79 years, who filled out an FFQ as part of eligibility screening for a diet modification component and/or a hormone replacement trial in a multicenter study of chronic disease prevention in postmenopausal women (Women's Health Initiative).For 26 FFQ questions, we recoded the low-fat diet choices of participants to a high-fat counterpart and recalculated energy and fat intakes. We then determined the decrease in energy and nutrient estimates attributable to adding low-fat options to the FFQ.Low-fat diet practices were widespread in this population. For example, 69% of respondents rarely or never ate skin on chicken, 76% rarely or never ate fat on meat, 36% usually drank nonfat milk, 52% usually ate low-fat or fat-free mayonnaise, 59% ate low-fat chips/snacks, and 42% ate nonfat cheese. These low-fat choices had substantial effects on energy and nutrient estimates. Absolute decreases (and mean percentage decreases) for energy and nutrient measures attributable to adding low-fat diet options to the FFQ were 196 kcal (11.4%) energy, 9 percentage points in percentage energy from fat (22.3%), 23.2 g fat (29.0%), and 9.6 g saturated fat (32.5%). Black and Hispanic women and women of lower socioeconomic status reported significantly fewer low-fat diet practices than white women and women of higher socioeconomic status.Failure to collect information on low-fat diet practices with an FFQ will result in an upward bias in estimates of energy and fat intake, and the amount of error will vary by the personal characteristics of respondents.
Publication
7
The evolution of the Women's Health Initiative: Perspectives from the NIHJacques Rossouw
Rossouw JE, Finnegan LP, Harlan WR, Pinn VW, Clifford C, McGowan JA. The evolution of the Women's Health Initiative: Perspectives from the NIH. J Am Med Womens Assoc. 1995 Mar-Apr;50(2):50-5.
none providedBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/7722207https://www.whi.org/researchers/bibliography/Manuscripts/ms7.pdf
The Women's Health Initiative (WHI) addresses some of the major health concerns of postmenopausal women. It is designed to test whether long-term preventive measures will decrease the incidence of cardiovascular disease, certain cancers, and fractures, and it seeks to find better predictors of future health and disease in older women. This report traces the evolution of the clinical trial and observational study (CT/OS) components of WHI from early planning in the 1980s to the current status of the WHI CT/OS as an integrated, ongoing clinical study. Particular attention is directed to the antecedent planning meetings and feasibility studies that formed the underpinnings of the WHI. The issues of hormone replacement therapy and of the optimal diet for postmenopausal women were investigated for almost a decade prior to WHI. However, no studies of sufficient size and duration to confidently test the value and risks of these approaches were initiated because of the cost and insufficient political commitment. The initiation of WHI in 1991 represents the confluence of scientific need and capability with the social priorities to improve the health and welfare of women.
Publication
8
Design of the Women's Health Initiative clinical trial and observational studyRoss Prentice
The Women's Health Initiative Study Group. Design of the Women's Health Initiative clinical trial and observational study. Control Clin Trials. 1998 Feb;19(1):61-109.
Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/9492970https://www.whi.org/researchers/bibliography/Manuscripts/ms8.pdf
The Women's Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components--dietary modification (DM) or hormone replacement therapy (HRT)--of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.
Publication
9
Approaches to monitoring the results of long-term disease prevention trials: Examples from the Women's Health InitiativeLaurence Freedman
Freedman L, Anderson G, Kipnis V, Prentice R, Wang CY, Rossouw J, Wittes J, DeMets D. Approaches to monitoring the results of long-term disease prevention trials: Examples from the Women's Health Initiative. Control Clin Trials. 1996 Dec;17(6):509-25.
Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/8974210https://www.whi.org/researchers/bibliography/Manuscripts/ms9.pdf
We contrast monitoring therapeutic trials with monitoring prevention trails. We argue that in monitoring prevention trials one should place more emphasis on formally defined global measures of health, not simply on a single targeted disease, particularly when an intervention may reduce the incidence of some diseases but increase the incidence of others. We describe one approach, illustrated by the Women's Health Initiative. For each of several sets of hypothetical interim results ("scenarios"), members of the Data and Safety Monitoring Committee (DSMC) were asked whether they would continue or stop the trial. In parallel with this exercise, various statistical methods of monitoring that are based on (1) the primary targeted disease, (2) a combination of various disease outcomes, or (3) a mixture of both were applied to these scenarios. One objective was to find a statistical approach that mirrors the majority view of the DSMC. A second objective was to stimulate discussion among DSMC members in preparation for their task of monitoring the trial as the real data become available. We found that no single method fully matched the majority vote of the DSMC. However, a mixed approach requiring the primary outcome to be significant and the global index to be "supportive," with separate monitoring of adverse effects, corresponded with the majority vote quite well. This approach maintains the emphasis on the primary hypothesis while assuring that broader safety and ethical issues of multiple diseases are incorporated.
Publication
11
The role of randomized controlled trials in assessing the benefits and risks of long-term hormone replacement therapy: Example of the Women's Health InitiativeRoss Prentice
Prentice R, Rossouw JR, Johnson, SR, Freedman LS, McTiernan A. The role of randomized controlled trials in assessing the benefits and risks of long-term hormone replacement therapy: Example of the Women's Health Initiative. Menopause. 1996;3:71-76
Clinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/ms11.pdf
Observational studies suggest that hormone replacement therapy among postmenopausal women may have important benefits, particularly in relation to heart disease and bone fractures, but may also convey important risks, most notably for breast cancer. The magnitude of these potential benefits and risks and the prevalence of use of hormone replacement therapy in the United States make the question of benefits versus risks a very pressing public health issue. This public health importance, along with the fact that reliable answers are likely to depend on accurate quantitative assessments of the impact of hormone replacement therapy on a range of clinical outcomes, implies a critical role for randomized controlled clinical trials of adequate size, duration, and quality in an overall replacement hormone research strategy. Some limitations of cohort and case‐control studies of long‐term hormone replacement therapy are briefly mentioned toward establishing the need for the type of logistically complicated clinical trial included in the Women's Health Initiative. This is followed by a description of the hormone replacement therapy component of the Women's Health Initiative Clinical Trial, along with some comments on the methods to be used for benefit‐versus‐risk monitoring and analysis of this trial. It is recommended that long‐term hormone replacement therapy, in the form of estrogen alone for hysterectomized women or estrogen plus progestin for women with a uterus, should be prescribed conservatively until more reliable data on risks and benefits are available from randomized controlled trials or from other sources.
Publication
12
Is insurance a more important determinant of healthcare access than perceived health? Evidence from the Women's Health InitiativeJudith Hsia
Hsia J, Kemper E, Sofaer S, Bowen D, Kiefe CI, Zapka J, Mason E, Lillington L, Limacher M. Is insurance a more important determinant of healthcare access than perceived health? Evidence from the Women's Health Initiative. J Womens Health Gend Based Med. 2000 Oct;9(8):881-9
insurance statusBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/11074954https://www.whi.org/researchers/bibliography/Manuscripts/ms12.pdf
Our objectives were to explore health insurance status and insurance type, adjusted for self-reported and perceived health variables, as determinants of having and using a usual care provider in the Women's Health Initiative (WHI) Observational Study (OS). This analysis describes insurance status in a large, diverse group of older women and tests the hypothesis that insurance was a key predictor of their access to healthcare in the mid-1990s. Multiple logistic regression analysis was used to evaluate determinants of having visited a usual healthcare provider within the proceeding 12 months, using cross-sectional information provided by a population-based cohort of 55,278 postmenopausal women. Five percent of women younger than 65 years and 0.2% of women 65 or older in the OS cohort lacked health insurance. Among the 31,684 women, aged 50-64 years, Hispanic women and those with fewer years of education and lower household income and who were current smokers were less likely, and those lacking insurance were the least likely, to have seen their healthcare provider within the preceding year. Among 23,594 women, aged 65-79 years, African American and Hispanic women and those with lower household income, and Medicare only and those who were current smokers, were less likely to have seen their healthcare provider within the preceding year. In both age groups, women with chronic medical conditions and poorer perceived health scores and those with prepaid insurance were more likely to have seen their healthcare provider. In the WHI OS, both health (self-reported and perceived) and type of health insurance remained independently associated with having visited a usual healthcare provider after multivariate adjustment for one another as well as for pertinent sociodemographic characteristics.
Publication
13
Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI)Sylvia Wassertheil-Smoller
Wassertheil-Smoller S, Shumaker S, Ockene J, Talavera GA, Greenland P, Cochrane B, Robbins J, Aragaki A, Dunbar-Jacob J. Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI). Arch Intern Med. 2004 Feb 9;164(3):289-98
depression, cardiovascular eventsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14769624https://www.whi.org/researchers/bibliography/Manuscripts/ms13.pdf
Subclinical depression, often clinically unrecognized, may pose increased risk of cardiovascular disease. Few studies have prospectively investigated cardiovascular events related to depression in older women. We describe prevalence, cardiovascular correlates, and relationship to subsequent cardiovascular events of depressive symptoms among generally healthy postmenopausal women.The Women's Health Initiative Observational Study followed up 93 676 women for an average of 4.1 years. Depression was measured at baseline with a short form of the Center for Epidemiological Studies Depression Scale. Risks of cardiovascular disease (CVD) events were estimated from Cox proportional hazards models adjusting for multiple demographic, clinical, and risk factor covariates.Current depressive symptoms above the screening cutoff point were reported by 15.8% of women. Depression was significantly related to CVD risk and comorbidity (odds ratios ranging from 1.12 for hypertension to 1.60 for history of stroke or angina). Among women with no history of CVD, depression was an independent predictor of CVD death (relative risk, 1.50) and all-cause mortality (relative risk, 1.32) after adjustment for age, race, education, income, diabetes, hypertension, smoking, high cholesterol level requiring medication, body mass index, and physical activity. Taking antidepressant medications did not alter the depression-associated risks associated.A large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD death and all-cause mortality, even after controlling for established CVD risk factors. Whether early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.
Publication
16
Differences between estimated caloric requirements and self-reported caloric intake in the Women's Health InitiativeJames Hebert
Hebert JR, Patterson RE, Gorfine M, Ebbeling CB, St Jeor ST, Chlebowski RT. Differences between estimated caloric requirements and self-reported caloric intake in the Women's Health Initiative. Ann Epidemiol. 2003 Oct;13(9):629-37
diet, energy intake, nutrition assessment, questionnaires, bias (epidemiology), womenBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14732302https://www.whi.org/researchers/bibliography/Manuscripts/ms16.pdf
To compare energy intake derived from a food frequency questionnaire (FFQ) with estimated energy expenditure in postmenopausal women participating in a large clinical study.A total of 161,856 women aged 50 to 79 years enrolled in the Women's Health Initiative (WHI) Observational Study (OS) or Clinical Trial (CT) [including the Diet Modification (DM) component] completed the WHI FFQ, from which energy intake (FFQEI) was derived. Population-adjusted total energy expenditure (PATEE) was calculated according to the Harris-Benedict equation weighted by caloric intakes derived from the National Health and Nutrition Examination Survey. Stepwise regression was used to examine the influence of independent variables (e.g., demographic, anthropometric) on FFQEI-PATEE. Race, region, and education were forced into the model; other variables were retained if they increased model explanatory ability by more than 1%.On average, FFQEI was approximately 25% lower than PATEE. Regression results (intercept=-799 kcal/d) indicated that body mass index (b=-23 kcal/day/kg.m(-2)); age (b=15 kcal/day/year of age); and study arm (relative to women in the OS, for DM women b=169 kcal/d, indicating better agreement with PATEE) increased model partial R(2)>.01. Results for CT women not eligible for DM were similar to those of women in the OS (b=14 kcal/d). There also were apparent differences by race (b=-152 kcal/d in Blacks) and education (b=-67 kcal/d in women with<high school).This large, carefully studied population confirms previous observations regarding underestimates in self-reported caloric intake relative to estimates of metabolic need in younger women, and those with higher weight, with less education, and in Blacks. These differences, along with effects related to intervention assignment, underline the need for additional research to enhance understanding of errors in dietary measurement.
Publication
17
Sexual orientation and health: Comparisons in the Women's Health Initiative sampleBarbara Valanis
Valanis BG, Bowen DJ, Bassford T, Whitlock E, Charney P, Carter RA. Sexual orientation and health: Comparisons in the Women's Health Initiative sample. Arch Fam Med. 2000 Sep-Oct;9(9):843-53
lesbians, prevalence, baseline characteristics, health status, psychosocial characteristicsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/11031391https://www.whi.org/researchers/bibliography/Manuscripts/ms17.pdf
Little is known about older lesbian and bisexual women. Existing research rarely compares characteristics of these women with comparable heterosexual women.To compare heterosexual and nonheterosexual women 50 to 79 years on specific demographic characteristics, psychosocial risk factors, screening practices, and other health-related behaviors associated with increased risk for developing particular diseases or disease outcomes.Analysis of data from 93,311 participants in the Women's Health Initiative (WHI) study of health in postmenopausal women, comparing characteristics of 5 groups: heterosexuals, bisexuals, lifetime lesbians, adult lesbians, and those who never had sex as an adult.Subjects were recruited at 40 WHI study centers nationwide representing a range of geographic and ethnic diversity.Postmenopausal women aged 50 to 79 years who met WHI eligibility criteria, signed an informed consent to participate in the WHI clinical trial(s) or observational study, and responded to the baseline questions on sexual orientation.Demographic characteristics, psychosocial risk factors, recency of screening tests, and other health-related behaviors as assessed on the WHI baseline questionnaire.Although of higher socioeconomic status than the heterosexuals, the lesbian and bisexual women more often used alcohol and cigarettes, exhibited other risk factors for reproductive cancers and cardiovascular disease, and scored lower on measures of mental health and social support. Notable is the 35% of lesbians and 81% of bisexual women who have been pregnant. Women reporting that they never had sex as an adult had lower rates of Papanicolaou screening and hormone replacement therapy use than other groups.This sample of older lesbian and bisexual women from WHI shows many of the same health behaviors, demographic, and psychosocial risk factors reported in the literature for their younger counterparts, despite their higher socioeconomic status and access to health care. The lower rates of recommended screening services and higher prevalence of obesity, smoking, alcohol use, and lower intake of fruit and vegetables among these women compared with heterosexual women indicate unmet needs that require effective interactions between care providers and nonheterosexual women.
Publication
19
Ethnic, socioeconomic, and lifestyle correlates of ity in U.S. women: The Women's Health InitiativeJoAnn Manson
Manson JE, Lewis CE, Kotchen JM, Allen C, Johnson KC, Stefanick M, Foreyt J, Klesges R, Tinker L, Noonan E, Perri M, Hall D. Ethnic, socioeconomic, and lifestyle correlates of obesity in U.S. women: The Women's Health Initiative. Clin J Womens Health. 2001;Dec 1(5):225-34.
obesity, ethnicity, socioeconomic status, physical activity, diet, womenBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms19.pdf
Publication
20
Relation of demographic factors, menstrual history, reproduction and medication use to sex hormones in postmenopausal womenAnne McTiernan
McTiernan A, Wu L, Barnabei VM, Chen C, Hendrix S, Modugno F, Rohan T, Stanczyk FZ, Wang CY; For the WHI Investigators. Relation of demographic factors, menstrual history, reproduction and medication use to sex hormone levels in postmenopausal women. Breast Cancer Res Treat. 2008 Mar;108(2):217-231. Epub 2007 May 22.
endogenous sex hormones, ethnicityClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18297397https://www.whi.org/researchers/bibliography/Manuscripts/ms20.pdf
W5
In postmenopausal women, levels of estrogens, androgens, and perhaps prolactin have been related to risk of breast and other hormonal cancers in women. However, the determinants of these hormone concentrations have not been firmly established. Associations among various demographic, menstrual, and reproductive factors, medication use and endogenous sex hormone concentrations (estradiol, free estradiol, estrone, estrone sulfate, testosterone, free testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), dihydrotestosterone, and prolactin) were evaluated in a cross-sectional analysis from a simple random sample of 274 postmenopausal women selected from the Women's Health Initiative Dietary Modification Trial. In multiple regression analyses on log-transformed hormones, the concentrations of DHEA, and DHEAS were negatively and statistically significantly associated with age (both beta=-0.03, P<0.001, respectively). Estradiol, estrone, DHEA, and free testosterone concentrations were higher in African-American than in non-Hispanic White women, but after multivariate adjustment the associations were statistically significant only for free testosterone (beta=0.38, P=0.01). Women who had a history of bilateral oophorectomy had a mean 35% lower testosterone concentration compared with women with at least one ovary remaining (beta=-0.43, P=0.002), and lower free testosterone (beta=-0.42, P=0.04) after multivariate adjustment. Women who reported regular use of NSAIDs had higher DHEA concentrations (beta=0.20, P=0.04) and lower prolactin concentrations (beta=-0.18, P=0.02) compared with non-users. These results suggest that while age, oophorectomy status, and NSAID use may be associated with selected sex hormone concentrations, few menstrual or reproductive factors affect endogenous sex hormones in the postmenopausal period.
Publication
21
Hypertension and its treatment in postmenopausal women: Baseline data from the Women's Health InitiativeSylvia Wassertheil-Smoller
Wassertheil-Smoller S, Anderson G, Psaty BM, Black HR, Manson J, Wong N, Francis J, Grimm R, Kotchen T, Langer R, Lasser N. Hypertension and its treatment in postmenopausal women: Baseline data from the Women's Health Initiative. Hypertension. 2000 Nov;36(5):780-9.
hypertension, demographic factors, risk factors, co-morbid factors, prevalence, treatmentObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/11082143https://www.whi.org/researchers/bibliography/Manuscripts/ms21.pdf
Little is known about the patterns of treatment and adequacy of blood pressure control in older women. The Women's Health Initiative, a 40-center national study of risk factors and prevention of heart disease, breast and colorectal cancer, and osteoporosis in postmenopausal women, provides a unique opportunity to examine these issues in the largest, multiethnic, best-characterized such cohort. Baseline data from the initial 98 705 women, aged 50 to 79 years, enrolled were analyzed to relate prevalence, treatment, and control of hypertension to demographic, clinical, and risk-factor covariates, and logistic regression analyses were performed to estimate odds ratios after adjusting for multiple potential confounders. Overall, 37.8% of the women had hypertension, which is defined as systolic blood pressure >/=140 mm Hg and/or diastolic blood pressure >/=90 mm Hg or being on medication for high blood pressure; 64.3% were treated with drugs, and blood pressure was controlled in only 36.1% of the hypertensive women, with lower rates of control in the oldest group. After adjustment for multiple covariates, current hormone users had higher prevalence than did nonusers (odds ratio 1.25). Hypertensive women had more comorbid conditions than did nonhypertensive women, and women with comorbidities were more likely to be treated pharmacologically. Diuretics were used by 44.3% of hypertensives either as monotherapy or in combination with other drug classes. As monotherapy, calcium channel blockers were used in 16%, angiotensin-converting enzyme inhibitors in 14%, beta-blockers in 9%, and diuretics in 14% of the hypertensive women. Diuretics as monotherapy were associated with better blood pressure control than any of the other drug classes as monotherapy. In conclusion, hypertension in older women is not being treated aggressively enough because a large proportion, especially those most at risk for stroke and heart disease by virtue of age, does not have sufficient blood pressure control.
Publication
22
Pelvic organ prolapse in the Women's Health Initiative: Gravity and graviditySusan Hendrix
Hendrix SL, Clark A, Nygaard I, Aragaki A, Barnabei V, McTiernan A. Pelvic organ prolapse in the Women's Health Initiative: Gravity and gravidity. Am J Obstet Gynecol. 2002 Jun;186(6):1160-6.
pelvic organ prolapse, prevalence, urinary incontinence, uterine prolapse, cystocele, rectocele, childbirth-related traumaClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12066091https://www.whi.org/researchers/bibliography/Manuscripts/ms22.pdf
The purpose of this study was to describe the prevalence of and correlates for pelvic organ prolapse.This was a cross-sectional analysis of women who enrolled in the Women's Health Initiative Hormone Replacement Therapy Clinical Trial (n = 27,342 women). Baseline questionnaires ascertained demographics and personal habits. A baseline pelvic examination assessed uterine prolapse, cystocele, and rectocele. Descriptive statistics and logistic regression models were used to investigate factors that were associated with pelvic organ prolapse.In the 16,616 women with a uterus, the rate of uterine prolapse was 14.2%; the rate of cystocele was 34.3%; and the rate of rectocele was 18.6%. For the 10,727 women who had undergone hysterectomy, the prevalence of cystocele was 32.9% and of rectocele was 18.3%. After controlling for age, body mass index, and other health/physical variables, African American women demonstrated the lowest risk for prolapse. Hispanic women had the highest risk for uterine prolapse. Parity and obesity were strongly associated with increased risk for uterine prolapse, cystocele, and rectocele.Pelvic organ prolapse is a common condition in older women. The risk for prolapse differs between ethnic groups, which suggests that the approaches to risk-factor modification and prevention may also differ. These data will help address the gynecologic needs of diverse populations.
Publication
24
Estimation of the correlation between nutrient intake measures under restricted samplingC.Y. Wang
Wang CY, Anderson GL, Prentice RL. Estimation of the correlation between nutrient intake measures under restricted sampling. Biometrics. 1999 Sep;55(3):711-7.
likelihood, measurement error, missing data, multiple imputation, nutritional epidemiologyBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/11314997https://www.whi.org/researchers/bibliography/Manuscripts/ms24.pdf
Food frequency questionnaires (FFQs) are commonly used to assess dietary intake in epidemiologic research. To evaluate the FFQ reliability, the commonly used approach is to estimate the correlation coefficient between the data given in FFQ and those in food records (for example, 4-day food records [4DFR]) for nutrients of interest. However, in a dietary intervention study, a criterion for eligibility may be to select participants who have baseline FFQ-measured dietary intake of percent energy from fat above a prespecified quantity. Other instruments, such as the 4DFR, may be subsequently administrated only to eligible participants. Under these circumstances, analysis without adjusting for the restricted population will usually lead to biased estimation of correlation coefficients and other parameters of interest. In this paper, we apply likelihood-based and multiple imputation (MI) methods to accommodate such incomplete data obtained as a result of the study design. A simulation study is conducted to examine finite sample performance of various estimators. We note that both the MI estimate and the maximum likelihood (ML) estimate based on a bivariate-normal model are not sensitive to departures from this normality assumption. This led us to investigate robustness properties of the ML estimator analytically. We present some data analyses from a dietary assessment study from the Women's Health Initiative to illustrate the methods.
Publication
25
Estrogen and progestin use and the QT interval in postmenopausal womenAlan Kadish
Kadish AH, Greenland P, Limacher MC, Frishman WH, Daugherty SA, Schwartz JB. Estrogen and progestin use and the QT interval in postmenopausal women. Ann Noninvasive Electrocardiol. 2004 Oct;9(4):366-74.
hormone replacement therapy, ECGClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15485516https://www.whi.org/researchers/bibliography/Manuscripts/ms25.pdf
To determine whether menopausal hormone therapy alters the QT interval in primarily healthy postmenopausal women.Despite well-known gender differences in myocardial repolarization that include a longer heart-rate-corrected QT interval (QT(C)) in women compared to men, the effects of menopausal hormone therapy on myocardial repolarization in women have not been well characterized.We studied 34,378 postmenopausal women participating in the dietary intervention component of the Women's Health Initiative. Cross-sectional associations were examined to assess possible effects of estrogen + progesterone on myocardial repolarization. Women who reported that they were never treated with menopausal hormone therapy (n = 12,451) were compared to women with a past use of menopausal hormone therapy (n = 3891), currently taking unopposed estrogen therapy (n = 9987), or combined current estrogen and progesterone therapy (n = 8049).Using analysis of covariance, the mean (+/-SEM) QT(C) interval was 423.1 +/- 0.2 milliseconds (ms) in those never treated with menopausal hormone therapy, 423.9 +/- 0.3 ms in past menopausal hormone therapy users, 425.6 +/- 0.2 ms in those currently on estrogen alone, and 424.0 +/- 0.2 ms in women currently on combined estrogen-progesterone therapy. Differences in mean QT(C) between those on estrogen alone and the other three groups were statistically significant. Comparisons of JT intervals, QT intervals, and linear corrected QT intervals among the groups yielded similar results.These results suggest that unopposed estrogen in menopausal women mildly prolongs myocardial repolarization, and the effect is reversed by progesterone. Whether these findings have clinical significance requires further study.
Publication
26
Special populations recruitment for the Women's Health Initiative: Successes and limitationsMona Fouad
Fouad MN, Corbie-Smith G, Curb D, Howard BV, Mouton C, Simon M, Talavera G, Thompson J, Wang CY, White C, Young R. Special populations recruitment for the Women's Health Initiative: Successes and limitations. Control Clin Trials. 2004 Aug;25(4):335-52.
special populations, recruitmentBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15296809https://www.whi.org/researchers/bibliography/Manuscripts/ms26.pdf
The Women's Health Initiative (WHI) is a study designed to examine the major causes of death and disability in women. This multi-arm, randomized, controlled trial of over 160,000 post-menopausal women of varying ethnic and socioeconomic backgrounds and a goal of 20% of the study participants from minority populations is perhaps one of the most challenging recruitment efforts ever undertaken. Of the two main study arms, the Clinical Trial (CT) and the Observational Study (OS), the CT arm recruitment goal was to randomize 64,500 postmenopausal women 50-79 years of age. Women enrolled in the study will be followed for a period of 8-12 years. Ten clinical centers, out of a total of 40 throughout the United States, were selected as minority recruitment centers on the basis of their history of interaction with and access to large numbers of women from certain population subgroups. WHI enrollment began in September 1993 and ended in December 1998, resulting in the randomization and enrollment of a total of 161,856 (17.5% minority) women participants (68,135 (18.5% minority) in the CT and 93,721 (16.7%) in the OS). Within the CT arm, WHI achieved 101.7% of the goal of 48,000 participants in the Dietary Modification (DM) component, and 99.4% of the goal of 27,500 in the hormone-replacement component (HRT), with 11.8% overlap between DM and HRT. Of those who expressed initial interest in WHI, African Americans had the highest randomization yields in the DM component and Hispanics had the highest in the HRT component (15.2% and 10.2%, respectively). Overall, mass mailing was the greatest source of randomized participants. In addition, minority clinics found community outreach, personal referrals, and culturally appropriate recruitment materials particularly effective recruitment tools. For minority recruitment, our findings suggest that the key to high yield is reaching the target population through appropriate recruitment strategies and study information that get their attention. Also, once minority subjects are reached, they tend to participate.
Publication
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The effects of insurance coverage and ethnicity on mammography utilization in a postmenopausal populationRuth Bush
Bush RA, Langer RD. The effects of insurance coverage and ethnicity on mammography utilization in a postmenopausal population. West J Med. 1998 Apr;168(4):236-40.
ethnicity, mammography, postmenopausalBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/9584660https://www.whi.org/researchers/bibliography/Manuscripts/ms27.pdf
Despite the effectiveness of mammography as a method to detect breast cancer in women ages 50 and older, many women do not obtain screening mammograms. This study used the self-reported mammography history and demographic information obtained during the screening of 2453 post-menopausal women ages 50 to 79 at the San Diego Women's Health Initiative (WHI) center. We used this data to examine individual and social factors that predict mammography use. The WHI center comprised two clinics, one of which focused on Hispanic recruitment and thus provided the opportunity to examine the roles of ethnicity, income, education, marital status, age, and access to medical services on mammography use. Bivariate analysis indicated that the following factors were all strongly associated with women having had a mammogram in the previous two years: having health insurance, a regular medical provider, an annual household income greater than $20,000, and a high-school diploma, as well as being 65 years or older or white (P < 0.001). Multiple logistic regression analysis demonstrated that, when adjusting for all of these factors, having a medical provider (P < 0.001) was significant. Having insurance (P = 0.04) was suggestive, but did not meet the multiple-comparisons significance cutoff of P = 0.006. After adjusting for the above factors, it was found that ethnicity was not significant. The results suggest that improved access to a regular provider could increase the use of screening mammography in underserved populations.
Approved Manuscript
28
Association between strenuous exercise and alcohol consumption at different stages of life with postmenopausal mental statusEtta Lindenfeld
data management system, multicenter studiesBoth OS and CT
Publication
35
Measurement characteristics of the Women's Health Initiative food frequency questionnaireRuth Patterson
Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T. Measurement characteristics of the Women's Health Initiative food frequency questionnaire. Ann Epidemiol. 1999 Apr;9(3):178-87.
FFQ, precisionBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/10192650https://www.whi.org/researchers/bibliography/Manuscripts/ms35.pdf
W30
The Women's Health Initiative (WHI) is the largest research program ever initiated in the United States with a focus on diet and health. Therefore, it is important to understand and document the measurement characteristics of the key dietary assessment instrument: the WHI food frequency questionnaire (FFQ).Data are from 113 women screened for participation in the WHI in 1995. We assessed bias and precision of the FFQ by comparing the intake of 30 nutrients estimated from the FFQ with means from four 24-hour dietary recalls and a 4-day food record.For most nutrients, means estimated by the FFQ were within 10% of the records or recalls. Precision, defined as the correlation between the FFQ and the records and recalls, was similar to other FFQs. Energy adjusted correlation coefficients ranged from 0.2 (vitamin B12) to 0.7 (magnesium) with a mean of 0.5. The correlation for percentage energy from fat (a key measure in WHI) was 0.6. Vitamin supplement use was common. For example, almost half of total vitamin E intake was obtained from supplements. Including supplemental vitamins and minerals increased micronutrient correlation coefficients, which ranged from 0.2 (thiamin) to 0.8 (vitamin E) with a mean of 0.6.The WHI FFQ produced nutrient estimate, that were similar to those obtained from short-term dietary recall and recording methods. Comparison of WHI FFQ nutrient intake measures to independent and unbiased measures, such as doubly labeled water estimates of energy expenditure, are needed to help address the validity of the FFQ in this population.
Publication
40
The associations between health and domestic violence in older women: Results of a pilot studyCharles Mouton
Mouton CP, Rovi S, Furniss K, Lasser NL. The associations between health and domestic violence in older women: Results of a pilot study. J Womens Health Gend Based Med. 1999 Nov;8(9):1173-9.
domestic violence, health status, women's healthObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/10595330https://www.whi.org/researchers/bibliography/Manuscripts/ms40.pdf
This study examined the association of domestic violence (DV) with the general physical and mental health of older women. This pilot cross-sectional survey studied 257 women, aged 50-79, who came for screening visits to the Observational Study arm of the Women's Health Initiative's (WHI) Newark, NJ, site between June 1995 and August 1996. A 27-item, interviewer-administered questionnaire was used to detect DV. To measure overall health status, we used questions from the Medical Outcomes Study Short Form 36. Of the 257 women interviewed, 82 (31.9%) had experienced DV at some point in their life; 51 (22.6%) had been threatened, and 31 (15%) had experienced physical assault. Women who were either physically assaulted or threatened had lower mental component summary (MCS) scores (50.0 versus 53.7). Women who had only been threatened had a mean MCS score of 49.7 compared with 53.8 for nonthreatened women. Both of these MCS scores indicate poorer mental health. DV, which about 1 in 4 women experience over their lifetime, has a negative relationship to health status. Women who have experienced DV have lower MCS scores than those who have not. They also tend to have lower physical component summary scores. These findings suggest the importance that detection and prevention of DV have for women's health.
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41
Cross-sectional correlates of fasting hyperinsulinaemia in post-menopausal women of different ethnic originAruna Pradhan
Pradhan AD, Manson JE, Hendrix SL, Johnson KC, Wagenknecht LE, Haan MN, Weidner G, Lacroix AZ, Cook NR. Cross-sectional correlates of fasting hyperinsulinaemia in post-menopausal women of different ethnic origin. Diabet Med. 2006 Jan;23(1):77-85.
hyperinsulinemia, anthropometric measurements, coronary risk factors, lifestyle factorsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16409570https://www.whi.org/researchers/bibliography/Manuscripts/ms41.pdf
In a large ethnically diverse nationwide sample of post-menopausal women we explored the relationship between fasting insulin levels, ethnicity, and a wide range of anthropometric, socio-economic, and lifestyle factors.Subjects were post-menopausal women aged 50-79 years without diagnosed diabetes mellitus comprising a subsample (n = 3500) of the Women's Health Initiative (WHI) Clinical Trial and Observational Study. In a cross-sectional survey at baseline, we analysed the association between ethnicity and fasting insulin using analysis of covariance procedures and identified independent correlates of hyperinsulinaemia, defined by the 75th percentile cut point for each ethnic group.Fasting insulin levels were higher among African-American and Hispanic women than among non-Hispanic White or Asian women. These differences persisted after adjustment for age, educational attainment, total and central body obesity, adult weight change, family history of diabetes, smoking status, alcohol consumption, use of menopausal hormone therapy and physical activity. Higher levels of body mass index, waist-hip ratio, adult weight gain, and lower levels of total and moderate or strenuous recreational activity were independent correlates of fasting hyperinsulinaemia. Habitual walking was also inversely associated with fasting insulin.In this cross-sectional analysis, fasting insulin levels were higher among African-American and Hispanic post-menopausal women as compared with non-Hispanic White and Asian women. In addition, obesity, adult weight gain, and low levels of moderate or strenuous physical activity were independently associated with hyperinsulinaemia.
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43
Sleep complaints of postmenopausal womenDaniel Kripke
Kripke DF, Brunner R, Freeman R, Hendrix S, Jackson RD, Masaki K, Carter RA. Sleep complaints of postmenopausal women. Clin J Women's Health. 2001;1:244-52.
Sleep, insomnia, depression, menopause, obesity.Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/21461131https://www.whi.org/researchers/bibliography/Manuscripts/ms43.pdf
AS11
Objective: To study correlates of sleep problems in postmenopausal women. Methods: Baseline questionnaire items related to sleep patterns and problems were administered to 98,705 postmenopausal women as part of the Clinical Trial and the Observational Study of the Women’s Health Initiative. Results: Less than 27% of the sample reported sleeping 8 hours or more. Many women reported that at least once a week they awoke several times at night (61%), fell asleep during quiet activities (52%), or reported other symptoms suggestive of insomnia or excessive daytime sleepiness. More frequent insomnia problems were reported among women who reported nocturnal sleep longer than the mode of 7 hours, as well as among women who reported very short sleep. Age, ethnicity, hormone replacement therapy, employment, marital status, diet, and season explained remarkably little of the variance in sleep duration or insomnia complaints; however, black women reported sleeping 0.45 hours on average less than whites, with the other minorities being intermediate between these groups. Conclusions: The results suggest that simple abbreviation of sleep and demographic factors may be less important in the sleep complaints of postmenopausal women than other possible factors. Cognitive-behavioral processes, depression, and obesity with apnea may be among the causes.
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51
Relationship of social support and social burden to repeated breast cancer screening in the Women's Health InitiativeCatherine Messina
Messina CR, Lane DS, Glanz K, West DS, Taylor V, Frishman W, Powell L. Relationship of social support and social burden to repeated breast cancer screening in the Women's Health Initiative. Health Psychol. 2004 Nov;23(6):582-94.
social networks, cancer screening,Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15546226https://www.whi.org/researchers/bibliography/Manuscripts/ms51.pdf
Direct and interactive effects of social support, social burden (caregiving, negative life events, and social strain), education, and income on repeated use of breast cancer screening among a large (N=55,278), national sample of postmenopausal women participating in the Women's Health Initiative observational study were examined. Repeated screening decreased as emotional/informational support and positive social interactions decreased (ps<.01). Repeated mammography decreased with frequent caregiving (p<.01). Less social strain reduced the frequency of repeated breast self-examinations (BSEs; ps<.01), but frequent caregiving and more negative life events increased repeated use of BSE (ps<.01). Interactive effects suggested that emotional/informational but not tangible support is associated with repeated mammography and clinical breast examinations (ps<.01) and may be particularly important among low-income older women, especially those burdened by caregiving.
Publication
55
Factor structure and measurement invariance of the Women's Health Initiative Insomnia Rating ScaleDouglas Levine
Levine DW, Kaplan RM, Kripke DF, Bowen DJ, Naughton MJ, Shumaker SA. Factor structure and measurement invariance of the Women's Health Initiative Insomnia Rating Scale. Psychol Assess. 2003 Jun;15(2):123-36.
sleep disturbance scale, ethnicity, normsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12847773https://www.whi.org/researchers/bibliography/Manuscripts/ms55.pdf
As part of the Women's Health Initiative Study, the 5-item Women's Health Initiative Insomnia Rating Scale (WHIIRS) was developed. This article summarizes the development of the scale through the use of responses from 66,269 postmenopausal women (mean age = 62.07 years, SD = 7.41 years). All women completed a 10-item questionnaire concerning sleep. A novel resampling technique was introduced as part of the data analysis. Principal-axes factor analysis without iteration and rotation to a varimax solution was conducted for 120,000 random samples of 1,000 women each. Use of this strategy led to the development of a scale with a highly stable factor structure. Structural equation modeling revealed no major differences in factor structure across age and race-ethnic groups. WHIIRS norms for race-ethnicity and age subgroups are detailed.
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59
Risk factors for kidney stones in postmenopausal women in the southern United StatesW. Dallas Hall
Hall WD, Pettinger M, Oberman A, Watts NB, Johnson KC, Paskett ED, Limacher MC, Hays J. Risk factors for kidney stones in older women in the southern United States. Am J Med Sci. 2001 Jul;322(1):12-8.
kidney stones, southern United States, risk factors, direct association, inverse associationBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/11465241https://www.whi.org/researchers/bibliography/Manuscripts/ms59.pdf
The occurrence of kidney stones is disproportionate in the southern region of the United States. Risk factors for the occurrence of kidney stones in this geographic area have not been reported previously.The Women's Health Initiative (WHI) is an ongoing multicenter clinical investigation of strategies for the prevention of common causes of morbidity and mortality among postmenopausal women. A case-control ancillary study was conducted on 27,410 (white or black) women enrolled in the 9 southern WHI clinical centers. There were 1,179 cases (4.3%) of kidney stones at the baseline evaluation. Risk factors for stone formation were assessed in cases versus age- and race-matched control subjects.Risk factors (univariate) included low dietary potassium (2,404 versus 2,500 mg/day, P = 0.006), magnesium (243 versus 253 mg/day, P = 0.003) and oxalate (330 versus 345 mg/day, P = 0.02) intake, as well as increased body mass index (28.5 versus 27.7 kg/m2, P = 0.001) and a history of hypertension (42% versus 34%, P = 0.001). A slightly lower dietary calcium intake (683 versus 711 mg/day, P = 0.04) was noted in case subjects versus control subjects, but interpretation was confounded by the study of prevalent rather than incident cases. Supplemental calcium intake >500 mg/day was inversely associated with stone occurrence.Multivariate risk factors for the occurrence of kidney stones in postmenopausal women include a history of hypertension, a low dietary intake of magnesium, and low use of calcium supplements.
Publication
60
The Women's Health Initiative Memory Study (WHIMS): A trial of the effect of estrogen therapy in preventing and slowing the progression of dementiaSally Shumaker
Shumaker SA, Reboussin BA, Espeland MA, Rapp SR, McBee WL, Dailey M, Bowen D, Terrell T, Jones BN. The Women's Health Initiative Memory Study (WHIMS): A trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials. 1998 Dec;19(6):604-21.
WHIMSMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/9875839https://www.whi.org/researchers/bibliography/Manuscripts/ms60.pdf
AS39
Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Women's Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older. WHIMS, an ancillary study to the Women's Health Initiative (WHI) funded by the National Institutes of Health, will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI. The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period. Participants will be followed annually for 6 years, receiving cognitive assessments via the Modified Mini-Mental State (3MS) Examination. Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation. Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia. WHIMS is designed to provide more than 80% statistical power to detect a 40% reduction in the rate of all-cause dementia, an effect that could have profound public health implications for older women's health and functioning.
Publication
62
Self-reported urogential symptoms in postmenopausal women: Women's Health InitiativeLisa Pastore
Pastore LM, Carter RA, Hulka BS, Wells E. Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative. Maturitas. 2004 Dec 10;49(4):292-303.
urogenital symptoms, self-report, correlatesBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15531125https://www.whi.org/researchers/bibliography/Manuscripts/ms62.pdf
To examine the prevalence and correlates of self-reported urogenital symptoms (dryness, irritation or itching, discharge, dysuria) among postmenopausal women aged 50-79.A cross-sectional analysis based on n=98,705 women enrolled in the US-based Women's Health Initiative observational study and clinical trials. Urogenital symptoms, symptom severity (mild, moderate, severe), and all covariates were self-reported through questionnaires at enrollment. Prevalence rates of each urogenital symptom were examined and logistic regression was used to identify potential correlates.Prevalence rates for each symptom were: dryness, 27.0%; irritation or itching, 18.6%; discharge, 11.1%; and dysuria, 5.2%. Four factors were correlated with two or more symptoms: Hispanic ethnicity (adjusted odds ratio (AOR)=2.1-3.1 versus white women across all symptoms), obesity (AOR=2.2 severe discharge versus none, AOR=3.6 severe irritation/itching versus none), treated diabetes (pills or shots) compared to no diabetes (AOR=2.4 severe dysuria versus none, AOR=3.2 severe irritation/itching versus none), and vaginal cream HRT/ERT compared to those who never used HRT/ERT (AOR=4.4 severe dryness versus none, AOR=4.6 severe irritation/itching versus none). Factors not associated with the symptoms included sexual activity, age, years since menopause, current smoking, marital status, gravidity, and natural versus surgical menopause.This is the first report to document urogenital symptoms by race/ethnicity among an exclusively postmenopausal population. We found an elevated prevalence of urogenital symptoms among women who are Hispanic, obese, and/or diabetic. Confirmation of our findings in these subgroups, and, if confirmed, analysis on why these populations are at greater risk, are areas for future research.
Publication
63
The importance of health insurance as a determinant of cancer screening: Evidence from the Women's Health InitiativeJudith Hsia
Hsia J, Kemper E, Kiefe C, Zapka J, Sofaer S, Pettinger M, Bowen D, Limacher M, Lillington L, Mason E. The importance of health insurance as a determinant of cancer screening: Evidence from the Women's Health Initiative. Prev Med. 2000 Sep;31(3):261-70.
insurance coverage, neoplasm/prevention & control, health services accessibilityObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/10964640https://www.whi.org/researchers/bibliography/Manuscripts/ms63.pdf
Amid current changes in health care access across the United States, the importance of health insurance status and insurance type relative to demographic, actual, and perceived health variables as determinants of screening for breast, colorectal, and cervical cancer is uncertain. This analysis evaluates the hypothesis that health insurance independently predicts cancer screening in the Women's Health Initia tive Observational Study cohort.Questionnaire data from 55,278 women en rolled in the Women's Health Initiative Observational Study between September 1994 and February 1997 were analyzed by multiple logistic regression to identify predictors of self-reported mammography within 2 years, Pap smear within 3 years, and stool guaiac or flexible sigmoidoscopy within 5 years.Positive determinants of reporting cancer screening were age, ethnic origin, household income, educational level, family history of cancer, having a usual care provider, time since last provider visit, and insurance status and type. Smoking, diabetes, and, among older women, prior cardiovascular events were negative determinants of cancer screening. Among women younger than 65, lacking health insurance or having fee-for-service insurance was strongly associated with failure to report cancer screening, independently of having or using a usual care provider and of demographics, self-perceived health, and health characteristics. Among women 65 and older, those with Medicare alone were less likely, whereas those with Medicare + prepaid insurance were more likely, to report cancer screening.In the Women's Health Initiative Obser vational Study, a large, diverse group of older women, health insurance type and status were among the most important determinants of cancer screening indepen dent of demographics, chronic health conditions, and self-perceived health characteristics.
Publication
66
Walking compared with vigorous exercise for the prevention of cardiovascular events in womenJoAnn Manson
Manson JE, Greenland P, LaCroix AZ, Stefanick ML, Mouton CP, Oberman A, Perri MG, Sheps DS, Pettinger MB, Siscovick DS. Walking compared with vigorous exercise for the prevention of cardiovascular events in women. N Engl J Med. 2002 Sep 5;347(10):716-25.
exercise, physical activity, walking, coronary heart disease, stroke, cardiovascular diseaseObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12213942https://www.whi.org/researchers/bibliography/Manuscripts/ms66.pdf
The role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse.We prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events.An increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and black women. Women in increasing quintiles of energy expenditure measured in metabolic equivalents (the MET score) had age-adjusted relative risks of coronary events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001). In multivariate analyses, the inverse gradient between the total MET score and the risk of cardiovascular events remained strong (adjusted relative risks for increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001). Walking and vigorous exercise were associated with similar risk reductions, and the results did not vary substantially according to race, age, or body-mass index. A brisker walking pace and fewer hours spent sitting daily also predicted lower risk.These prospective data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index. Prolonged sitting predicts increased cardiovascular risk.
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67
Yogurt consumption is associated with healthy behavior in postmenopausal womenYasmin Mossavar-Rahmani
Mossavar-Rahmani Y, Garland CF, Caan B, Hebert JR, Wodarski LA, Vitolins MZ, Himes JH, Parker LM. Yogurt consumption is associated with healthy behavior in postmenopausal women. Clin J Women's Health. 2002;2(3):128-134.
breast cancer, colorectal cancer. dietary components, yogurt consumptionObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms67.pdf
Background: The purpose of this study was to examine lifestyle and health patterns of yogurt consumers in order to enhance the analysis between yogurt consumption and health outcomes. Methods: We assessed the socio-cultural and behavioral characteristics of 2,173 consumers and 1,223 nonconsumers of yogurt in a sample of postmenopausal women participating in the Observational Study (OS) of the Women’s Health Initiative (WHI). Results: Mean yogurt consumption was 1.3 cups/week (standard deviation, 2.0). Thirty-six percent of the sample did not consume yogurt. Yogurt consumers were, on the average, younger, taller, lighter, wealthier, better educated, and were more likely to be white and married than nonconsumers. They also exhibited healthier behavior including being more physically active, having a lower rate of smoking, and consuming a healthier diet, notably a significantly higher intake of calcium, fiber, vitamins A and D, lycopene, fruits, and vegetables and lower intake of total and saturated fats.
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Correlates of serum lypocene in older womenDeborah Casso
Casso D, White E, Patterson RE, Agurs-Collins T, Kooperberg C, Haines PS. Correlates of serum lycopene in older women. Nutr Cancer. 2000;36(2):163-169.
serum lycopene, lifestyle, demographics, biochemical factorsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/10890026https://www.whi.org/researchers/bibliography/Manuscripts/ms69.pdf
Experimental and epidemiological evidence suggests that lycopene, a predominant carotenoid found in human serum, may reduce the risk of certain cancers. We examined the association of dietary, physiological, and other factors with serum lycopene concentrations in a subsample of 946 postmenopausal women participating in the Women's Health Initiative. Pearson partial correlation coefficients and linear regression coefficients were calculated after adjustment for age, ethnicity, and serum low-density-lipoprotein (LDL) cholesterol. Serum lycopene was correlated with serum LDL cholesterol (r = 0.23) and dietary lycopene (r = 0.17, both p < 0.001). Individual food items found to be correlated with serum lycopene after adjustment included fresh tomatoes or tomato juice (r = 0.11), cooked tomatoes, tomato sauce, or salsa (r = 0.17), and spaghetti with meat sauce (r = 0.19, all p < 0.01). Age and body mass index were negatively associated with serum lycopene levels (both p < 0.001). Serum lycopene levels were highest in the summer and highest for those living in the northeastern United States. If we postulate that high serum lycopene levels reduce cancer risk, it becomes apparent that we have limited ability to detect this association from studies of lycopene intake. An understanding of factors associated with serum lycopene levels can be useful for the interpretation of studies of dietary lycopene and disease risk.
Publication
70
Correlates of serum alpha- and gamma-tocopherol in the Women's Health InitiativeEmily White
White E, Kristal AR, Shikany JM, Wilson AC, Chen C, Mares-Perlman JA, Masaki KH, Caan BJ. Correlates of serum alpha- and gamma-tocopherol in the Women's Health Initiative. Ann Epidemiol. 2001 Feb;11(2):136-44.
tocopherol, Vitamin E, lifestyle, demographics, biochemical factorsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/11164130https://www.whi.org/researchers/bibliography/Manuscripts/ms70.pdf
There is increasing evidence that vitamin E (primarily alpha- and gamma-tocopherol) may reduce the risk of cardiovascular disease and some cancers, therefore it is important to understand factors that influence blood levels.The correlates of serum alpha- and gamma-tocopherol were investigated among participants in the Women's Health Initiative (WHI), a 40-site disease prevention trial. Subjects were 1047 postmenopausal women aged 50-79 years, who provided fasting blood specimens and detailed information on diet, supplement use, and other factors at entry to the study (1994-96).Total serum cholesterol and triglycerides were highly correlated with serum alpha- and gamma-tocopherol concentrations and were controlled for in all analyses along with age, ethnicity and body mass index (BMI). Alpha and gamma-tocopherol were strongly negatively correlated (partial r = -0.69). The strongest predictor of serum tocopherols was average daily intake of vitamin E from supplements (partial r = 0.60 for alpha, r = -0.54 for gamma). Other factors associated with increased alpha- and/or decreased gamma-tocopherol concentrations were serum retinol and carotenoids, supplemental vitamin C, alpha-tocopherol intake from food, dietary fiber, and Hispanic ethnicity. Factors associated with lower alpha- and/or higher gamma-tocopherol concentrations included gamma-tocopherol intake from food, total fat intake, and BMI. Age, income, hormone use, and geographic location were "spuriously" associated with serum tocopherol levels through their association with supplement use, i.e., there was no such association among the subset of women not taking supplements.Vitamin E intake from supplements and BMI are the major independent predictors of serum tocopherol levels in women, whereas dietary factors only play a small role.
Publication
71
The Women's Health Initiative: Goals, rationale, and current statusJames Liu
Liu JH. The Women's Health Initiative: Goals, rationale, and current status. Menopausal Medicine. 1998;6(2):1-4
women's Health InitiativeBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms71.pdf
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72
Postmenopausal bone loss and its relationship to oral bone lossMarjorie Jeffcoat
Jeffcoat MK, Lewis CE, Reddy MS, Wang CY, Redford M. Post-menopausal bone loss and its relationship to oral bone loss. Periodontol. 2000. 2000 Jun;23:94-102.
osteoporosis, bone, periodontitis, clinical trials, humanBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/11276771https://www.whi.org/researchers/bibliography/Manuscripts/ms72.pdf
AS9
Publication
74
Breast cancer survivors' health-related quality of life: Racial differences and comparisons with noncancer controlsElectra Paskett
Paskett ED, Alfano CM, Davidson MA, Andersen BL, Naughton MJ, Sherman A, McDonald PG, Hays J. Breast cancer survivors' health-related quality of life: Racial differences and comparisons with noncancer controls. Cancer. 2008 Dec 1;113(11):3222-30. Epub 2008 Oct 30.
breast cancer, quality of life, survivorsObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18973178https://www.whi.org/researchers/bibliography/Manuscripts/ms74.pdf
Small samples with few minority women and/or the absence of comparisons to peers without cancer histories have limited previous research suggesting racial differences in breast cancer survivors' health-related quality of life (HRQoL). This study not only compared HRQoL of African American and white breast cancer survivors, but also compared the HRQoL of these women to that of same-race women with no cancer history.Data from the Women's Health Initiative-Observational Study were used, including 5021 cancer survivors and 88,532 women without a history of cancer. Multivariate regression analyses estimated differences in breast cancer survivors' baseline HRQoL (RAND36), depressive symptoms (CES-D short-form), and sleep quality (WHIIRS).African American breast cancer survivors reported worse physical functioning and general health compared with white survivors. Among African Americans, survivors reported worse role limitations due to physical health, pain, general health, and vitality than women without a history of cancer. This was most evident in those with more recent diagnoses. Most significant differences between groups were small in magnitude (Cohen d = .21-.36).These results add to the increasing knowledge of cancer disparities by showing that African American women have small, but clinically meaningful, decrements in physical HRQoL compared with white survivors and with African American women without cancer. Because African American women also face diagnosis with higher grade tumors and higher breast cancer mortality, more research is needed to examine the physical and psychosocial experiences of African American breast cancer survivors to elucidate the mechanisms leading to poorer outcomes.
Publication
76
Differences in eating pattern labels between maintainers and nonmaintainers in the Women's Health InitiativeShana Hopkins
Hopkins S, Burrows E, Bowen DJ, Tinker LF. Differences in eating pattern labels between maintainers and nonmaintainers in the Women's Health Initiative. J Nutr Educ. 2001 Sep-Oct;33(5):278-83.
labeling, maintenance, dietary, low-fat, behavioralClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12031178https://www.whi.org/researchers/bibliography/Manuscripts/ms76.pdf
To describe how a sample of women in the Women's Health Initiative Dietary Modification Trial (WHIDM) labeled a healthy eating pattern and to compare these labels to their dietary maintenance.Participants completed a food frequency questionnaire and were divided into two maintenance groups, based on the percentage of energy derived from fat in their diets. Individual, semistructured interviews with the same subjects elicited information on labels they use to describe a healthy eating pattern.Subjects were 100 postmenopausal women, 50 to 79 years of age, free of breast and colorectal cancer, and participating in a dietary intervention that consisted of 20% or less energy from fat.Percentage of energy from fat in the diet and labels used to define a healthy eating pattern.Multivariate analysis.The label "consistent/patterned" was a predictor of dietary nonmaintenance (p <.05).Future studies should use this information to re-educate nonmaintainers on compliance issues.
Publication
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Lack of a relation between vitamin and mineral antioxidants and bone mineral density: Results from the Women's Health InitiativeRandi Wolf
Wolf RL, Cauley JA, Pettinger M, Jackson R, Lacroix A, Leboff MS, Lewis CE, Nevitt MC, Simon JA, Stone KL, Wactawski-Wende J. Lack of a relation between vitamin and mineral antioxidants and bone mineral density: Results from the Women's Health Initiative. Am J Clin Nutr. 2005 Sep;82(3):581-8.
correlates, dietary factors; nutrition; bone mineral density; ethnicityBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16155271https://www.whi.org/researchers/bibliography/Manuscripts/ms78.pdf
Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass.This study cross-sectionally examined whether higher dietary intakes, total intakes, and serum concentrations of antioxidants may be associated with higher bone mineral density (BMD).Total hip (and subregions), spine, and total-body BMDs were measured in 11,068 women aged 50-79 y enrolled in the Women's Health Initiative Observational Study and Clinical Trial at 3 clinics. Antioxidant intakes from diet (vitamin A, retinol, beta-carotene, vitamin C, vitamin E, and selenium) were estimated by using a self-reported food-frequency questionnaire. Antioxidants from supplements were estimated with an interviewer-administered questionnaire. A random subset (n = 379) had serum concentrations of retinol, carotenoids, and tocopherols measured.After adjustment for important BMD-related covariates, increasing intakes of antioxidants were not independently associated with BMD. A significant interaction effect was observed between intake of total vitamin C (lower three-fourths compared with highest one-fourth) and use of hormone therapy (HT) (P < 0.01). The beneficial effect of current HT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body (P < 0.045), spine (P = 0.03), and total-hip BMDs (P = 0.029).Our results do not support independent associations between dietary intake, total intake, or serum concentrations of antioxidants and BMD in women participating in the Women's Health Initiative. The extent to which HT use may interact with vitamin C intake and BMD warrants further exploration.
Publication
80
Insulin resistance and weight gain in postmenopausal women of diverse ethnic groupsBarbara Howard
Howard BV, Adams-Campbell L, Allen C, Black H, Passaro M, Rodabough RJ, Rodriguez BL, Safford M, Stevens VJ, Wagenknecht LE. Insulin resistance and weight gain in postmenopausal women of diverse ethnic groups. Int J Obes Relat Metab Disord. 2004 Aug;28(8):1039-47.
insulin resistance, weight gain, fasting glucose, insulinBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15254486https://www.whi.org/researchers/bibliography/Manuscripts/ms80.pdf
This study was conducted to examine the influence of insulin resistance on weight change in postmenopausal women of various ethnic groups.Data were obtained from 3389 women (60% White, 20% Black, 12% Hispanic, and 8% Asian/Pacific Islander), ages 50-79, enrolled in either the Women's Health Initiative Clinical trial or Observational Study, whose blood samples were selected randomly from the full cohort of 161 809 women for analyses.Glucose, insulin, and lipids were measured on fasting serum samples drawn at baseline and after 3 y of follow-up. Weight, height, waist circumference, and blood pressure were measured. Physical activity and energy intake were assessed via questionnaire. Insulin resistance was estimated using the HOMA (homeostasis model) calculation.Average age was 62 y, average BMI (body mass index) was 27.4 kg/m2, and average weight change was a gain of 0.4 kg in 3 y. In a multivariate analysis, insulin resistance and insulin concentrations were independent predictors of increases in weight in White women (P=0.002 and 0.004, respectively) and in the combined group (P=0.027 and 0.039). For the whole group, after adjustment for other covariates, those in the highest quartile of insulin resistance gained 0.4 kg in 3 y, whereas those in the lowest quartile lost 0.06 kg. Similar trends were found for insulin resistance and weight gain in Hispanic and Asian/Pacific Islander women, but they did not reach statistical significance. In Black women, no relation was seen between either insulin or insulin resistance and weight change. A significant interaction between obesity and insulin resistance was observed (P=0.002 for White women and 0.032 for the whole group), so that there is weight gain with increasing insulin resistance in the leaner women, but weight loss with increasing insulin resistance in the most obese.Insulin resistance appears to be a predictor of weight gain in postmenopausal women, except for the most obese women. The effect is more pronounced in women who have a lower BMI, and the effect was not seen in the Black women who as a group had a higher BMI.
Publication
83
Recreational physical activity and the risk of breast cancer in postmenopausal women: The Women's Health Initiative Cohort StudyAnne McTiernan
McTiernan A, Kooperberg C, White E, Wilcox S, Coates R, Adams-Campbell LL, Woods N, Ockene J. Recreational physical activity and the risk of breast cancer in postmenopausal women: The Women's Health Initiative Cohort Study. JAMA. 2003 Sep 10;290(10):1331-6.
breast cancer, physical activity, etiologyBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12966124https://www.whi.org/researchers/bibliography/Manuscripts/ms83.pdf
Women who are physically active have a decreased risk for breast cancer, but the types, amounts, and timing of activity needed are unknown.To prospectively examine the association between current and past recreational physical activity and incidence of breast cancer in postmenopausal women.Prospective cohort study in 74 171 women aged 50 to 79 years who were recruited by 40 US clinical centers from 1993 through 1998.Incident invasive and in situ breast cancer.We documented 1780 newly diagnosed cases of breast cancer over a mean follow-up of 4.7 years. Compared with less active women, women who engaged in regular strenuous physical activity at age 35 years had a 14% decreased risk of breast cancer (relative risk [RR], 0.86; 95% confidence interval [CI], 0.78-0.95). Similar but attenuated findings were observed for strenuous physical activity at ages 18 years and 50 years. An increasing total current physical activity score was associated with a reduced risk for breast cancer (P =.03 for trend). Women who engaged in the equivalent of 1.25 to 2.5 hours per week of brisk walking had an 18% decreased risk of breast cancer (RR, 0.82; 95% CI, 0.68-0.97) compared with inactive women. Slightly greater reduction in risk was observed for women who engaged in the equivalent of 10 hours or more per week of brisk walking. The effect of exercise was most pronounced in women in the lowest tertile of body mass index (BMI) (<24.1), but also was observed for women in the middle tertile of BMI (24.1-28.4).These data suggest that increased physical activity is associated with reduced risk for breast cancer in postmenopausal women, longer duration provides most benefit, and that such activity need not be strenuous.
Publication
84
Research staff turnover and participant adherence in the Women's Health InitiativeMarie Jackson
Jackson M, Berman N, Huber M, Snetselaar L, Granek I, Boe K, Milas C, Spivak J, Chlebowski RT. Research staff turnover and participant adherence in the Women's Health Initiative. Control Clin Trials. 2003 Aug;24(4):422-35.
staff turnover, adherenceClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12865036https://www.whi.org/researchers/bibliography/Manuscripts/ms84.pdf
Maintaining participant adherence is a prerequisite for successful completion of randomized controlled trials requiring long-term follow-up. While patient characteristics influencing adherence are well studied, the influence of contact with clinical staff on this process has received almost no attention. To address this issue the authors evaluated the association of turnover in key clinical research staff with measures of participant adherence to protocol requirements at 40 clinical centers participating in the Women's Health Initiative (WHI), a large multicenter study. Key staff turnover in positions with potential influence on maintaining participant adherence in the Dietary Modification Clinical Trial (DM-CT) and the two Menopausal Hormone Therapy Clinical Trials (HT-CT) of the WHI was determined at each clinical center. Three prospectively established measures of participant adherence for the DM-CT and HT-CT were related to key staff turnover at each clinical center by staff category. More frequent turnover of the clinic practitioner, clinic manager, and principal investigator positions was significantly (p<0.05) associated with lower participant adherence in the HT-CT but was not associated with DM-CT participant adherence. More frequent turnover of the lead nutritionist was not associated with HT-CT participant adherence but was significantly (p<0.05) associated with one measure of decreased DM-CT participant adherence, as would be expected since the lead nutritionist did not typically see the HT-CT participants. These significant and plausible associations suggest that providing consistent contact with key staff in randomized, controlled clinical trials may facilitate long-term participant adherence. Further prospective study exploring process evaluation of the provider side of controlled trial conduct is indicated.
Publication
85
The Women's Health Initiative: Rationale, design and progress reportSusan Johnson
Johnson SR, Anderson GL, Barad DH, Stefanick ML. The Women's Health Initiative: Rationale, design, and progress report. J Br Menopause Soc. 1999;5:155-9.
WHI, clinical trial,  hormone replacement therapyClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/ms85.pdf
Publication
86
The effects of physical and emotional status on adherence to a low-fat dietary pattern in the Women's Health InitiativeLesley Tinker
Tinker LF, Perri MG, Patterson RE, Bowen DJ, McIntosh M, Parker LM, Sevick MA, Wodarski LA. The effects of physical and emotional status on adherence to a low-fat dietary pattern in the Women's Health Initiative. J Am Diet Assoc. 2002 Jun;102(6):789-800, 888
dietary adherence, low-fat eating pattern, postmenopausal women, self-monitoring, quality-of-life, depressionClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12067044https://www.whi.org/researchers/bibliography/Manuscripts/ms86.pdf
To examine whether the effects of physical and emotional status on adherance to a low-fat (20% energy) dietary pattern are mediated by participation in an intervention program (attending sessions and self-monitoring).The Baron and Kenny mediator model, a series of 4 regression analyses, was used to evaluate whether: a) physical and emotional status predicted program participation, b) program participation predicted dietary adherence, c) physical and emotional status factors predicted dietary adherence, and, ultimately d) the effects of physical and emotional status on dietary adherence were mediated by program participation.Data from 13,277 postmenopausal women randomly assigned to the low-fat intervention arm of the Women's Health Initiative Dietary Modification Trial.The nutrition goals for women randomly assigned to the low-fat intervention were to reduce total fat intake to 20% or less of energy from fat and to consume 5 or more fruit/vegetable servings daily and 6 or more grain servings daily.Year 1 program participation (degree of attending group sessions and submitting fat scores) and adherence to the low-fat dietary pattern (percent energy from fat) as predicted by baseline physical and emotional status (eight SF-36 Health Survey subscales).Participating in the dietary intervention program reduced (mediated) the negative effect of poorer mental health on dietary adherence by 15%. Additional findings included that a 10% increase in physical functioning increased session attendance by 0.4% (P<.001) and a 10% increase in mental health predicted a decrease in percent energy from fat of 0.3% (P<.001). Program participation had a marked effect on dietary adherence: a 10% increase in session attendance predicted a 1.2% decrease in percent energy from fat (P<.001).Understanding and using instruments to assess the physical and emotional status of a target population will help dietetic professionals promote healthful dietary change and maintenance.
Publication
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Estimating normal hemogram values for postmenopausal womenAnnlouise Assaf
Assaf A, Carleton R, Miller M, Coccio E. Estimating normal hemogram values for postmenopausal women. Clin J Women's Health. 2000;1(1):23-28.
leukocyte count, red cell count, platelet count, hemoglobin, hematocrit, post-menopausal womenBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms88.pdf
Objectives: “Complete” blood counts are a commonly obtained laboratory analysis. The Women’s Health Initiative (WHI), as part of its study entry process, has obtained hemograms on a large number of postmenopausal women between the ages of 50 and 79. An effort has been made by WHI to obtain a study population closely resembling the postmenopausal women in the United States. This report uses data from the Southeastern New England WHI Vanguard Clinical Center to focus on the implications of the lack ofa standard reference range for the parameter of the white blood cell count. Leukopenia defined by the laboratory normal range led to this analysis. Methods: The hemograms ofover 6,600 postmenopausal women were analyzed. Distribution curves, 95% confidence interval limits, and cut points at the 2.5 and 97.5 percentile levels were obtained for hemoglobin, hematocrit, platelet count, and white blood cell count. Normal ranges from the 11 Rhode Island acute care hospitals were also obtained. Results: Each of the 4 parameters have approximately normal distributions in this postmenopausal population. The normal ranges, most strikingly for white blood cell count, differ from the heterogeneous ranges used by Rhode Island Hospitals. For this population ofpostmenopausal women, the best estimate ofnormal ranges would seem to be: White blood cell count 3,500 to 9,600 mm3; 11.8 to 15.4 g/dL for hemoglobin; 34.7% to 45.2% for hematocrit; and 147,000 to 354,000 mm3 for platelets.
Publication
91
Compliance with National Cholesterol Education Program dietary and lifestyle guidelines among older women with self-reported hypercholesterolemia. The Women's Health InitiativeJudith Hsia
Hsia J, Rodabough R, Rosal MC, Cochrane B, Howard BV, Snetselaar L, Frishman WH, Stefanick ML. Compliance with National Cholesterol Education Program dietary and lifestyle guidelines among older women with self-reported hypercholesterolemia. The Women's Health Initiative. Am J Med. 2002 Oct 1;113(5):384-92.
self-report, hyperlipidemia, adherence, dietary guidelines, ancillary studyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12401533https://www.whi.org/researchers/bibliography/Manuscripts/ms91.pdf
Dietary therapy remains the first line of treatment for patients with high blood cholesterol levels. Among free-living persons, compliance with National Cholesterol Education Program (NCEP) dietary recommendations is uncertain.We performed a cross-sectional, baseline analysis of 91,627 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Among women with self-reported hypercholesterolemia, we ascertained factors associated with compliance with National Cholesterol Education Program dietary recommendations, defined for the Step II diet as <or=30% of total calories from fat, <7% of calories from saturated fat, and daily dietary cholesterol <200 mg.Of the 13,777 participants who reported having high cholesterol levels requiring drug therapy, only 20% reported total fat, saturated fat, and dietary cholesterol consumption consistent with Step II dietary goals. Factors associated with Step II dietary compliance included having a college degree (odds ratio [OR] = 1.26; 95% confidence interval [CI]: 1.14 to 1.40), a prior cardiovascular event (OR = 1.48; 95% CI: 1.28 to 1.70), and consumption of five or more daily servings of fruits or vegetables (OR = 3.0; 95% CI: 2.7 to 3.3). Being married, smoking, a sedentary lifestyle, and a higher body mass index were all associated with reduced compliance (all P <0.0001). In the subsample in which plasma lipid levels were measured, dietary compliance was associated with higher levels of low-density lipoprotein cholesterol (P = 0.02).Since the inception of the NCEP in 1985, health care providers, public health programs, and patients have not successfully implemented the dietary recommendations.
Publication
92
Comparison of self-report, hospital discharge codes, and adjudication of cardiovascular events in the Women's Health InitiativeSusan Heckbert
Heckbert SR, Kooperberg C, Safford MM, Psaty BM, Hsia J, McTiernan A, Gaziano JM, Frishman WH, Curb JD. Comparison of self-report, hospital discharge codes, and adjudication of cardiovascular events in the Women's Health Initiative. Am J Epidemiol. 2004 Dec 15;160(12):1152-8.
cardiovascular events, self-report, adjudicationBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15583367https://www.whi.org/researchers/bibliography/Manuscripts/Ms92-v2.pdf
Limited information is available from large clinical investigations about the agreement among sources of diagnoses for endpoints. The authors used data from the Women's Health Initiative clinical trials and observational study from January 1994 to November 2000 to evaluate the agreement among self-report, hospital discharge codes, and two different levels of physician review of medical records for cardiovascular endpoints. For myocardial infarction, stroke, pulmonary embolism, and venous thrombosis, the agreement of hospital discharge codes or self-report with review by study physicians at clinical centers was substantial (kappa = 0.64-0.84). For coronary revascularization, agreement among these sources of information was substantial to almost perfect (kappa = 0.79-0.92), but for angina, congestive heart failure, and peripheral vascular disease, concordance was only fair to moderate (kappa = 0.37-0.56), indicating that these endpoints remain difficult to classify reliably. Agreement between physician adjudicators at clinical centers and central physician adjudicators was substantial to almost perfect (kappa = 0.67-0.94). The findings also suggest that, for the endpoint of myocardial infarction, physician review of events with hospital discharge codes for angina and congestive heart failure is an important source of validated events, and for stroke, review of all events with cerebrovascular codes is important.
Publication
93
Fat intake in husbands of participants in the dietary modification component of the Women's Health InitiativeJames Shikany
Shikany JM. Fat intake in husbands of participants in the dietary modification component of the Women's Health Initiative. Nutr Res. 2002;22:577-586.
diet, dietary fats, fat-restricted diet, diet records, intervention studies, questionnaires, spousesBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms93.pdf
Intakes of total, saturated, monounsaturated, and polyunsaturated fats over the previous three months were assessed in husbands (or domestic partners) of women in the Dietary Modification component of the Women’s Health Initiative (WHI) randomized to either the low-fat intervention or control arm for at least one year at the Birmingham, Alabama WHI Clinical Center. Dietary intake was estimated with a semi-quantitative food frequency questionnaire mailed to each husband. Intervention husbands consumed 35.0% of total energy from total fat compared to 37.4% in control husbands (p<0.01), 11.9% of total energy from saturated fat compared to 12.6% in control husbands (p<0.05), 13.7% of total energy from monounsaturated fat compared to 14.7% in control husbands (p<0.005), and 6.7% of total energy from polyunsaturated fat compared to 7.2% in control husbands (p<0.05). The WHI intervention to reduce dietary fat in postmenopausal women had the additional effect of reducing fat intake in their husbands.
Approved Manuscript
94
The modifying effect of socio-cultural status on risk factors for type 2 diabetes in older Mexican American womenDeborah Parra-Medina
Type 2 diabetes, Mexican American, obesity, acculturation, SESObservational Study
Publication
95
The effects of widowhood on physical and mental health, health behaviors, and health outcomes: The Women's Health InitiativeSara Wilcox
Wilcox S, Evenson KR, Aragaki A, Wassertheil-Smoller S, Mouton CP, Loevinger BL. The effects of widowhood on physical and mental health, health behaviors, and health outcomes: The Women's Health Initiative. Health Psychol. 2003 Sep;22(5):513-22.
widowhood, death of spouse, health behaviors, health, disease risk factorsObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/14570535https://www.whi.org/researchers/bibliography/Manuscripts/ms95.pdf
This study examined whether widowhood was associated with physical and mental health, health behaviors, and health outcomes using a cross-sectional (N=72,247) and prospective (N=55,724) design in women aged 50-79 years participating in the Women's Health Initiative observational study (85.4% White). At baseline, married women reported better physical and mental health and generally better health behaviors than widowed women. Whereas women who remained married over the 3-year period showed stability in mental health, recent widows experienced marked impairments and longer term widows showed stability or slight improvements. Both groups of widows reported more unintentional weight loss over the 3-year period. Changes in physical health and health behaviors were inconsistent, with generally small effect sizes. Findings underscore the resilience of older women and their capacity to reestablish connections, but point to the need for services that strengthen social support among women who have difficulty during this transition.
Publication
98
Antioxidant supplement use in Women's Health Initiative participantsJames Shikany
Shikany JM, Patterson RE, Agurs-Collins T, Anderson G. Antioxidant supplement use in Women's Health Initiative participants. Prev Med. 2003 Mar;36(3):379-87.
antioxidants, supplements, vitamin C, vitamin E, caroteneBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12634029https://www.whi.org/researchers/bibliography/Manuscripts/Ms98.pdf
Although antioxidant supplements are widely available and commonly used in the United States, there is a lack of detailed information on their use, including types of supplements used, doses, duration of use, and changes in use over time.Antioxidant supplement use was assessed in participants in the Clinical Trial (n = 68,133) and Observational Study (n = 93,676) of the Women's Health Initiative. In-person interviews and a computerized inventory procedure were used to collect data on supplement use during baseline clinic visits from 1993 through 1998.Antioxidant supplements were widely consumed. For example, 55.5% of participants reported taking supplemental vitamin C in some form. Supplement use was positively associated with age, education, and physical activity. Most antioxidants were consumed through multivitamins. However, high doses were commonly consumed from single supplements, with 43.9% using single vitamin C supplements taking >500 mg and 86.1% using single vitamin E supplements taking >200 IU daily. Except for beta-carotene, there were increases in the use of all supplements from 1993 to 1998.This report demonstrates the feasibility of collecting comprehensive dietary supplement use data in large studies. These data may aid in the design of supplement use questionnaires, which could help to prevent misclassification error in epidemiologic studies of diet and disease.
Publication
99
Risk factor clustering in the insulin resistance syndrome and its relationship to cardiovascular disease in postmenopausal white, black, hispanic, and Asian/Pacific Islander womenBarbara Howard
Howard BV, Criqui MH, Curb JD, Rodabough R, Safford MM, Santoro N, Wilson AC, Wylie-Rosett J. Risk factor clustering in the insulin resistance syndrome and its relationship to cardiovascular disease in postmenopausal white, black, hispanic, and Asian/Pacific Islander women. Metabolism. 2003 Mar;52(3):362-71.
insulin resistance, coronary heart disease, cardiovascular diseaseObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12647277https://www.whi.org/researchers/bibliography/Manuscripts/ms99.pdf
The aim of this study was to examine how major components of the insulin resistance (IR) syndrome relate to each other and to cardiovascular disease (CVD) in postmenopausal women in 4 ethnic groups. Baseline data from the Women's Health Initiative (WHI) on 3,083 50- to 79-year-old women (1,635 white, 802 black, 390 Hispanic, and 256 Asian/Pacific Islander) were examined. Participants underwent a personal interview and a physical examination, blood samples were drawn, and a detailed cardiovascular history was ascertained. Factor analysis was used to assess the clustering and interdependence of groups of CVD-related IR syndrome variables. Four factors were identified. An obesity factor included IR in all groups and had a significant association with CVD in white (P =.0001) and Hispanic (P =.0024) women. A dyslipidemia factor (high-density lipoprotein [HDL], triglycerides, and HDL2: total HDL ratio) also included insulin and IR and was significantly correlated with CVD in black (P=.0006) and Hispanic (P =.0217) women and had a borderline association in white women (P =.068). Total and low-density lipoprotein (LDL) cholesterol did not relate to CVD in any group. Blood pressure was related weakly to CVD in white women (P =.0434) and strongly in black women (P =.0095). Components of the IR syndrome appear to be associated with CVD in postmenopausal women, although the magnitude of these relationships differed by ethnicity.
Publication
100
Frequency and predictive value of a mammographic recommendation for short-interval follow-upShagufta Yasmeen
Yasmeen S, Romano PS, Pettinger M, Chlebowski RT, Robbins JA, Lane DS, Hendrix SL. Frequency and predictive value of a mammographic recommendation for short-interval follow-up. J Natl Cancer Inst. 2003 Mar 19;95(6):429-36.
mammography, Recall, Category III, CostBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12644536https://www.whi.org/researchers/bibliography/Manuscripts/ms100.pdf
A recommendation for short-interval follow-up of "probably benign finding" is associated with up to 11% of screening mammograms, but its predictive value for breast cancer is unclear. We examined the predictive values (i.e., the percentage of women with a diagnosis of breast cancer 2 years after a short-interval follow-up recommendation) and likelihood ratios (derived from the pretest and post-test odds of breast cancer in the Women's Health Initiative sample) for breast cancer that are associated with a recommendation for short-interval follow-up among postmenopausal women.We performed a longitudinal analysis of a prospective cohort of 68 126 postmenopausal women (aged 50-79 years) who were participating in clinical trials as part of the Women's Health Initiative at 40 centers across the United States. Eligible participants had screening mammograms at baseline and at least 2 years of follow-up that included a repeat mammography. Outcomes measured were breast cancer events at 1 and 2 years after baseline and the results of subsequent mammograms. All P values were two-sided.A total of 2927 (5%) of the 58 408 eligible women had baseline mammograms that included recommendations for short-interval follow-up. The incidence of breast cancer for women with a short-interval follow-up recommendation was 1.0% at 2 years after the baseline mammogram compared with breast cancer incidences of 0.6% and 0.5% for women whose baseline mammograms were described as "benign" and "negative," respectively. Across the 40 participating centers, the prevalence of short-interval follow-up recommendations among baseline mammograms varied from 1.2% to 9.8% (P<.001), even when the analysis was adjusted for key variables in regression models. Centers reporting higher frequencies of such recommendations did not have lower positive predictive values for breast cancer than centers reporting lower frequencies. The likelihood ratio for breast cancer after a recommendation for short-interval follow-up on a subsequent mammogram was 2.20 (95% confidence interval = 1.65 to 2.86).Having a mammographic recommendation for short-interval follow-up was associated with a low positive predictive value for breast cancer among postmenopausal women during a 2-year follow-up. This result suggests that the current criteria for this recommendation-repeat mammography within 6 months-should be reconsidered.
Publication
102
Association between cardiovascular outcomes and antihypertensive drug treatment in older womenSylvia Wassertheil-Smoller
Wassertheil-Smoller S, Psaty B, Greenland P, Oberman A, Kotchen T, Mouton C, Black H, Aragaki A, Trevisan M. Association between cardiovascular outcomes and antihypertensive drug treatment in older women. JAMA. 2004 Dec 15;292(23):2849-59.
hypertension, CVD, myocardial InfarctionObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15598916https://www.whi.org/researchers/bibliography/Manuscripts/ms102.pdf
Diuretic-based therapy is at least as effective as newer classes of agents for hypertension. However, many patients with hypertension require treatment with more than 1 drug class to achieve blood pressure control. The relative benefits or risks of 2-drug-class combinations are not well known.To prospectively evaluate if there are differences in cardiovascular mortality among postmenopausal women with hypertension but no history of cardiovascular disease (CVD) treated with different classes of antihypertensive agents, singly or in combination.Women with hypertension enrolled in the Women's Health Initiative Observational Study, a longitudinal multicenter cohort study of 93 676 women aged 50 to 79 years at baseline (1994-1998), assessed for a mean of 5.9 years.Relationship between baseline use of ACE inhibitors, beta-blockers, calcium channel blockers, or diuretics, or a combination of these, and incidence of coronary heart disease, stroke, and CVD mortality.Among 30,219 women with hypertension but no history of CVD, 19,889 were receiving pharmacological antihypertensive treatment, of whom 11,294 (57%) [corrected] were receiving monotherapy with an ACE inhibitor, beta-blocker, calcium channel blocker, or diuretic, and 4493 (23%) were treated at baseline with a combination of diuretic plus either ACE inhibitor, beta-blocker, or calcium channel blocker or ACE inhibitor plus calcium channel blocker. Monotherapy with calcium channel blockers vs diuretics was associated with greater risk of CVD death (hazard ratio, 1.55; 95% confidence interval, 1.02-2.35), controlling for multiple covariates. Women treated with a diuretic plus a calcium channel blocker had an 85% greater risk of CVD death vs those treated with a diuretic plus a beta-blocker, after adjustment for age, race, smoking, high cholesterol levels requiring medication, body mass index, physical activity, use of hormone therapy, and diabetes. After exclusion of women with diabetes the hazard ratio was 2.16 (95% confidence interval, 1.16-4.03). Analyses adjusting for propensity to be receiving a particular treatment did not change the results. For morbid events of coronary heart disease or stroke, diuretics plus ACE inhibitors or calcium channel blockers did not differ from diuretics plus beta-blockers.Among women with hypertension but no history of CVD, a 2-drug-class regimen of calcium channel blockers plus diuretics was associated with a higher risk of CVD mortality vs beta-blockers plus diuretics. Risks were similar for ACE inhibitors plus diuretics and beta-blockers plus diuretics. Monotherapy with diuretics was equal or superior to other monotherapy in preventing CVD complications of high blood pressure.
Publication
103
The Women's Health Initiative: Recruitment complete--looking back and looking forwardJacques Rossouw
Rossouw JE, Hurd S. The Women's Health Initiative: Recruitment complete--looking back and looking forward. J Womens Health. 1999 Jan-Feb;8(1):3-5.
Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/10094073https://www.whi.org/researchers/bibliography/Manuscripts/ms103.pdf
Publication
104
Promoting adherence and retention to clinical trials in special populations:  A Women's Health Initiative workshopSara Wilcox
Wilcox S, Shumaker SA, Bowen DJ, Naughton MJ, Rosal MC, Ludlam SE, Dugan E, Hunt JR, Stevens S. Promoting adherence and retention to clinical trials in special populations: A Women's Health Initiative workshop. Control Clin Trials. 2001 Jun;22(3):279-89.
adherence, retention, special populations, workshop, staff trainingBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/11384790https://www.whi.org/researchers/bibliography/Manuscripts/ms104.pdf
This paper describes a Women's Health Initiative workshop on promoting adherence and retention in randomized clinical trials among ethnic minority women, participants of lower socioeconomic status, and older women. Workshop objectives were: (1) to increase knowledge of demographic and cultural characteristics of diverse groups, (2) to increase awareness of how diversity can affect interactions in clinical research, (3) to explore how research staff behavior can influence adherence and retention, and (4) to increase knowledge of strategies to enhance adherence and retention in special populations. The workshop emphasized the importance of understanding beliefs, values, and experiences that are common in diverse groups of individuals, while at the same time recognizing and respecting individual differences that result from varying life circumstances and experiences. We discuss strategies to increase cultural competence, reduce stereotypes and discrimination, and create a culturally relevant and sensitive research environment.
Publication
105
Retention of under-served women in clinical trials: A focus group studyRhoda Johnson
Johnson RE, Williams RD, Nagy MC, Fouad MN. Retention of under-served women in clinical trials: A focus group study. Ethn Dis. 2003 Spring;13(2):268-78.
retention, minority, socioeconomic factors, ancillary studyClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12785425https://www.whi.org/researchers/bibliography/Manuscripts/ms105.pdf
More information is needed to understand how women view their participation in clinical trials. As part of the formative evaluation phase of a 4-year National Cancer Institute funded study, researchers associated with the "Community Retention Intervention Study" (CRIS) conducted focus groups to identify additional data on the underlying issues regarding the retention and compliance of under-served women in clinical trials. Six focus groups were conducted: 3 were age-based, and 3 involved participants of the Women's Health Initiative (WHI) clinical trial component in Birmingham, Alabama. A total of 62 women, between 18 and 87 years of age, participated in the sessions: 79% were African-American and 52% reported incomes below dollar 20,000. The qualitative data analysis revealed that women were more inclined to participate in a clinical trial if they, or a family member, would benefit. Non-compliance with study protocols was generally a result of complications or unwanted side effects of treatments. Focus group data were used to develop retention and compliance strategies for the CRIS study. Findings suggest that focus group data can be used effectively to develop retention and compliance strategies specific to under-served women.
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Vigorous leisure activity through women's adult life: The Women's Health Initiative Observational Cohort StudyKelly Evenson
Evenson KR, Wilcox S, Pettinger M, Brunner R, King AC, McTiernan A. Vigorous leisure activity through women's adult life: The Women's Health Initiative Observational Cohort Study. Am J Epidemiol. 2002 Nov 15;156(10):945-53.
physical activity, trackingObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12419767https://www.whi.org/researchers/bibliography/Manuscripts/ms107.pdf
This study described differences in vigorous activity participation recalled across the life span, assessed whether reports of past vigorous activity were associated with current participation, and examined factors associated with participation in current vigorous activity among women. After the exclusion of women aged 50-54 years, the study population included 71,837 multiethnic postmenopausal women aged 55-79 years who were participating in the Women's Health Initiative Observational Cohort Study, 1993-1998. Vigorous activity was assessed retrospectively for ages 18, 35, and 50 years and currently at enrollment into the study (median age, 65 years). Current participation in vigorous activity (>3 days/week) was low and consistent across racial/ethnic groups (13-16%). The prevalence of vigorous activity declined with age, with the largest decrease in vigorous activity occurring after age 50 years for all racial/ethnic groups. Current vigorous activity was generally higher among women with a lower body mass index, not currently smoking, in excellent general health, and of higher socioeconomic status across racial/ethnic groups. These data suggest that a lower prevalence of vigorous activity in the postmenopausal period is part of a complex of health-related attitudes and behaviors that transcends race/ethnicity. The perimenopausal period may be a critical juncture at which targeted and tailored interventions may help to achieve maintenance of physical activity into the postmenopausal period.
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Cross-sectional geometry, bone strength, and bone mass in the proximal femur in black and white postmenopausal womenDorothy Nelson
Nelson DA, Barondess DA, Hendrix SL, Beck TJ. Cross-sectional geometry, bone strength, and bone mass in the proximal femur in black and white postmenopausal women. J Bone Miner Res. 2000 Oct;15(10):1992-7.
bone density, hip structure, cross-sectional geometry, proximal femur, ethnic differencesClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/11028452https://www.whi.org/researchers/bibliography/Manuscripts/ms108.pdf
Osteoporosis is characterized by both a low bone mass and a disruption of the architectural arrangement of bone tissue, leading to decreased skeletal strength and increased fracture risk. Although there are well-known ethnic differences in bone mass and fracture risk, little is known about possible ethnic differences in bone structure. Therefore, we studied cross-sectional geometry in the hip in a sample of postmenopausal black and white women in order to investigate ethnic differences that might contribute to differences in bone strength and ultimately hip fracture risk. We recruited 371 postmenopausal black and white women who were entering the Women's Health Initiative (WHI) clinical trials in Detroit. Bone density measurements of the proximal femur were done by dual-energy X-ray absorptiometry (DXA) using a Hologic 1000 Plus bone densitometer. The DXA data were used for hip structure analysis, which treats the entire proximal femur as a continuous curved beam from the proximal shaft to the femoral neck. This permits the analysis of cross-sectional geometric properties in two narrow regions corresponding to thin (5 mm) cross-sectional slabs seen on edge. The results indicate significant ethnic differences in bone density, cross-sectional geometry, and dimensional variables. Specifically, the black women have a significantly higher bone density in both locations (10.1% and 4.1% for the neck and shaft, respectively); greater cross-sectional geometric properties in the neck (ranging from 6.1% to 11.6%), but a smaller endocortical diameter in the neck (3.6%). There are fewer significant differences in cross-sectional geometry in the shaft location. Our data suggest that the spatial distribution of bone is arranged in the femoral neck to resist greater loading in black women compared with white women.
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111
Effects of fat content on fat hedonics: Cognition or taste?Deborah Bowen
Bowen D, Green P, Vizenor N, Vu C, Kreuter P, Rolls B. Effects of fat content on fat hedonics: Cognition or taste? Physiol Behav. 2003 Feb;78(2):247-53.
dietary fat, behavior, ancillary studyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12576122https://www.whi.org/researchers/bibliography/Manuscripts/ms111.pdf
Understanding and perhaps overriding preferences for fat is important, given the relationship between higher dietary fat consumption and poorer health. We have examined the roles of potential mechanisms for differences in fat preference: actual fat content and expected fat content. The subjects were women (n=192, ages=50-69) recruited to a study of low-fat dietary change. Subjects were randomized to one of the four cells: participants received either a high- or low-fat milkshake at baseline, and half of each group was told that their milkshake was low in fat and the other half high in fat. Women who received a high-fat milkshake consumed more grams than women who received a low-fat milkshake. Women who expected low-fat shakes reported liking them more than those who expected high-fat milkshakes. These data indicate that both physiology and cognition play a role in determining consumption of high- and low-fat foods.
Publication
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Results of an adjunct dietary intervention program in the Women's Health InitiativeDeborah Bowen
Bowen D, Ehret C, Pedersen M, Snetselaar L, Johnson M, Tinker L, Hollinger D, Ilona L, Bland K, Sivertsen D, Ocke D, Staats L, Beedoe JW. Results of an adjunct dietary intervention program in the Women's Health Initiative. J Am Diet Assoc. 2002 Nov;102(11):1631-7.
dietary intervention, motivational interviewing, ancillary studyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12449286https://www.whi.org/researchers/bibliography/Manuscripts/ms112.pdf
The purpose of this study was to develop, implement, and evaluate the efficacy of an intensive intervention program (IIP) based on motivational interviewing to motivate participants within the dietary study of the Women's Health Initiative (WHI) to meet the study's nutritional goals.WHI dietary intervention participants (n=175) from 3 clinical centers were randomly assigned to either intervention or control status. Participants assigned to IIP intervention received 3 individual motivational interviewing contacts from a dietitian, plus the usual WHI Dietary Intervention. Participants randomly assigned to IIP control received the usual WHI dietary modification (DM) Intervention. Percent of energy from fat was estimated at study baseline and at follow-up (1 year later) using the WHI Food Frequency Questionnaire.The change in percent energy from fat between IIP baseline and IIP 1-year follow-up was -1.2% for IIP intervention participants and +1.4% for IIP control participants, giving an overall difference of 2.6% (P<.001). Participants having the highest IIP baseline fat intake (>30% energy) showed the largest overall change in percent energy from fat between IIP baseline and IIP follow-up.The results of this study indicate that a protocol based on motivational interviewing and delivered through contacts with trained dietitians is an efficacious way to further lower dietary fat intake among participants exposed to ongoing intervention. These data will be useful in future intervention situations when there is a need to increase motivation to change.
Publication
113
Prior oral contraception and postmenopausal fracture: A Women's Health Initiative observational cohort studyDavid Barad
Barad D, Kooperberg C, Wactawski-Wende J, Liu J, Hendrix SL, Watts NB. Prior oral contraception and postmenopausal fracture: A Women's Health Initiative observational cohort study. Fertil Steril. 2005 Aug;84(2):374-83.
fracture rate, oral contraceptivesBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16084878https://www.whi.org/researchers/bibliography/Manuscripts/ms113.pdf
To test for the possible association of past oral contraceptive (OC) use and incident fracture after menopause.A prospective cohort of 93,725 postmenopausal women.Forty Women's Health Initiative (WHI) clinical centers across the United States.Ethnically diverse 93,725 volunteer postmenopausal women, 50 to 79 years old.None.The main outcome was self-reported incident first fracture assessed prospectively by annual questionnaire.The adjusted relative hazard (HR) for fracture among past OC users was 1.07 (95% CI, 1.01-1.15). Among women without any postmenopausal hormone treatment, past OC use for < or =5 years led to an HR of 1.15 (95% CI, 1.04-1.27) and for past OC use >5 years led to an HR of 1.09 (95% CI, 0.97-1.23) compared with never users.This study does not support the idea that past OC use protects against later fracture.
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Prevalence and 3-year incidence of abuse among postmenopausal womenCharles Mouton
Mouton CP, Rodabough RJ, Rovi SL, Hunt JL, Talamantes MA, Brzyski RG, Burge SK. Prevalence and 3-year incidence of abuse among postmenopausal women. Am J Public Health. 2004 Apr;94(4):605-12.
physical abuse, emotional abuse, prevalence, incidenceObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15054013https://www.whi.org/researchers/bibliography/Manuscripts/ms115.pdf
We examined prevalence, 3-year incidence, and predictors of physical and verbal abuse among postmenopausal women.We used a cohort of 91,749 women aged 50 to 79 years from the Women's Health Initiative. Outcomes included self-reported physical abuse and verbal abuse.At baseline, 11.1% reported abuse sometime during the prior year, with 2.1% reporting physical abuse only, 89.1% reporting verbal abuse only, and 8.8% reporting both physical and verbal abuse. Baseline prevalence was associated with service occupations, having lower incomes, and living alone. At 3-year follow-up, 5.0% of women reported new abuse, with 2.8% reporting physical abuse only, 92.6% reporting verbal abuse only, and 4.7% reporting both physical and verbal abuse.Postmenopausal women are exposed to abuse at similar rates to younger women; this abuse poses a serious threat to their health.
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Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States)Libby Morimoto
Morimoto LM, White E, Chen Z, Chlebowski RT, Hays J, Kuller L, Lopez AM, Manson J, Margolis KL, Muti PC, Stefanick ML, McTiernan A. Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States). Cancer Causes Control. 2002 Oct;13(8):741-51.
breast cancer, anthropometrics, waist/hip ratio, etiology, obesityObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12420953https://www.whi.org/researchers/bibliography/Manuscripts/ms120.pdf
Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women.We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50-79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993-1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference.Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) >31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62-3.93), compared to slimmer women (baseline BMI < 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88-2.01).Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.
Approved Manuscript
121
Quality of life in healthy women and in breast cancer survivorsMary Haan
quality of life, breast cancer, survivors, WHEL, WHI,
Publication
122
Statin use, clinical fracture, and bone density in postmenopausal women: Results from the Women's Health Initiative Observational StudyAndrea LaCroix
LaCroix AZ, Cauley JA, Pettinger M, Hsia J, Bauer DC, McGowan J, Chen Z, Lewis CE, McNeeley SG, Passaro MD, Jackson RD. Statin use, clinical fracture, and bone density in postmenopausal women: Results from the Women's Health Initiative Observational Study. Ann Intern Med. 2003 Jul 15;139(2):97-104.
statin, fractureObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12859159https://www.whi.org/researchers/bibliography/Manuscripts/ms122.pdf
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to stimulate bone formation in laboratory studies, both in vitro and in vivo. While early epidemiologic studies showed lower risk for hip fracture among statin users than nonusers, subsequent studies have produced mixed results.To examine the association of statin use with incidence of hip, lower arm or wrist, and other clinical fractures and with baseline levels of bone density.Prospective study.Women's Health Initiative Observational Study conducted in 40 clinical centers in the United States.93 716 postmenopausal women ages 50 to 79 years.Rates of hip, lower arm or wrist, and other clinical fractures were compared among 7846 statin users and 85 870 nonusers over a median follow-up of 3.9 years. In 6442 women enrolled at three clinical centers, baseline levels of total hip, posterior-anterior spine, and total-body bone density measured by using dual-energy x-ray absorptiometry were compared according to statin use.Age-adjusted rates of hip, lower arm or wrist, and other clinical fractures were similar between statin users and nonusers regardless of duration of statin use. The multivariate-adjusted hazard ratios for current statin use were 1.22 (95% CI, 0.83 to 1.81) for hip fracture, 1.04 (CI, 0.85 to 1.27) for lower arm or wrist fracture, and 1.11 (CI, 1.00 to 1.22) for other clinical fracture. Bone density levels did not statistically differ between statin users and nonusers at any skeletal site after adjustment for age, ethnicity, body mass index, and other factors.Statin use did not improve fracture risk or bone density in the Women's Health Initiative Observational Study. The cumulative evidence does not warrant use of statins to prevent or treat osteoporosis.
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126
Influences on older women's adherence to a low-fat diet in the Women's Health InitiativeMilagros Rosal
Kearney MH, Rosal MC, Ockene JK, Churchill LC. Influences on older women's adherence to a low-fat diet in the Women's Health Initiative. Psychosom Med. 2002 May-Jun;64(3):450-7.
aging, health behavior, dietary behavior change, qualitative research, womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12021418https://www.whi.org/researchers/bibliography/Manuscripts/ms126.pdf
AS75
Most studies of dietary change during aging have focused on maintaining adequate intake by impaired elderly, and little is known about factors affecting dietary change for preventive purposes in older individuals. The purpose of this exploratory study was to determine the major behavioral influences on older women's adherence to a dietary fat reduction intervention.A diverse sample of 92 women aged 55 to 80 was recruited from two East Coast sites of the Women's Health Initiative. All the women were participating in the dietary modification arm of WHI, had received the same dietary instruction, and were in the maintenance phase of the intervention. The women were classified by nutritionists as adherent or nonadherent to a diet limiting fat intake to <20% of total calories. Focus groups and telephone interviews were conducted, and textual data were coded and sorted using content analysis techniques within the four categories of the Stimuli-Organismic Factors-Response Repertoire-Consequences (SORC) behavioral model. Frequencies of responses within categories were tabulated and compared qualitatively.Adherent women were more likely to report assertiveness, a lifelong commitment to reduced dietary fat, satisfaction with their lifestyle changes, and having applicable knowledge and skills. Nonadherent women reported more difficulty resisting negative emotions and prior food preferences and habits; they were also more concerned about negative responses from others.Enhancing adherence of older women to a dietary fat reduction program will require shifting priorities away from conforming to social pressure and using high-fat foods for personal satisfaction and moving toward enhancing motivation and commitment to long-term health.
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128
Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: Prospective analysis from the Women's Health Initiative observational studyAruna Pradhan
Pradhan AD, Manson JE, Rossouw JE, Siscovick DS, Mouton CP, Rifai N, Wallace RB, Jackson RD, Pettinger MB, Ridker PM. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: Prospective analysis from the Women's Health Initiative Observational Study. JAMA. 2002 Aug 28;288(8):980-7
inflammation, biomarkers, coronary heart disease, myocardial infarction, womenObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12190368https://www.whi.org/researchers/bibliography/Manuscripts/ms128.pdf
AS83
Postmenopausal hormone replacement therapy (HRT) has been shown to elevate C-reactive protein (CRP) levels. Several inflammatory biomarkers, including CRP, are associated with increased cardiovascular risk. However, whether the effect of HRT on CRP represents a clinical hazard is unknown.To assess the association between baseline levels of CRP and interleukin 6 (IL-6) and incident coronary heart disease (CHD) and to examine the relationship between baseline use of HRT, CRP, and IL-6 levels as they relate to subsequent vascular risk.Prospective, nested case-control study of postmenopausal women, forming part of the Women's Health Initiative, a large, nationwide, observational study. Among 75 343 women with no history of cardiovascular disease or cancer, 304 women who developed incident CHD were defined as cases and matched by age, smoking status, ethnicity, and follow-up time with 304 study participants who remained event free during a median observation period of 2.9 years.Incidence of first myocardial infarction or death from CHD.Median baseline levels of CRP (0.33 vs 0.25 mg/dL; interquartile range [IQR], 0.14-0.71 vs 0.10-0.47; P<.001) and IL-6 (1.81 vs 1.47 pg/mL; IQR, 1.30-2.75 vs 1.05-2.15; P<.001) were significantly higher among cases compared with controls. In matched analyses, the odds ratio (OR) for incident CHD in the highest vs lowest quartile was 2.3 for CRP (95% confidence interval [CI], 1.4-3.7; P for trend =.002) and 3.3 for IL-6 (95% CI, 2.0-5.5; P for trend <.001). After additional adjustment for lipid and nonlipid risk factors, both inflammatory markers were significantly associated with a 2-fold increase in odds for CHD events. As anticipated, current use of HRT was associated with significantly elevated median CRP levels. However, there was no association between HRT and IL-6. In analyses comparing individuals with comparable baseline levels of either CRP or IL-6, those taking or not taking HRT had similar CHD ORs. In analyses stratified by HRT, we observed a positively graded relationship between plasma CRP levels and the OR for CHD among both users and nonusers of HRT across the full spectrum of baseline CRP.These prospective findings indicate that CRP and IL-6 independently predict vascular events among apparently healthy postmenopausal women and that HRT increases CRP. However, use or nonuse of HRT had less importance as a predictor of cardiovascular risk than did baseline levels of either CRP or IL-6.
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Tissue plasminogen activator antigen and D-dimer as markers for atherothrombotic risk among healthy postmenopausal womenAruna Pradhan
Pradhan AD, LaCroix AZ, Langer RD, Trevisan M, Lewis CE, Hsia JA, Oberman A, Kotchen JM, Ridker PM. Tissue plasminogen activator antigen and D-dimer as markers for atherothrombotic risk among healthy postmenopausal women. Circulation. 2004 Jul 20;110(3):292-300. Epub 2004 Jul 6.
thrombosis, biomarkers, coronary heart disease, myocardial infarction, womenObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15238458https://www.whi.org/researchers/bibliography/Manuscripts/ms129.pdf
AS83
Plasma markers of fibrinolytic function are associated with incident coronary events among several, but not all, prospective epidemiologic investigations of healthy individuals. Few studies have evaluated this relationship in women. In addition, although menopausal hormone therapy (HT) may alter markers of fibrinolytic function, the relevance of this effect for coronary risk assessment has not been studied.In a prospective, nested case-control study among 75 343 postmenopausal women without prior cardiovascular disease or cancer, we evaluated the relationships of elevated tissue plasminogen activator (tPA) antigen and D-dimer with subsequent first coronary heart disease events over a median period of 2.9 years. Baseline levels of both biomarkers were higher among 304 cases compared with 304 controls matched on age, smoking status, ethnicity, and length of follow-up; median values were 9.0 versus 7.4 ng/mL (P<0.001) for tPA antigen and 27.6 versus 23.4 ng/mL (P=0.001) for D-dimer. In matched-pairs analyses, the odds ratio in the highest versus lowest quartile of tPA antigen was 3.5 (95% CI, 2.1 to 5.8; P trend <0.001) and for D-dimer was 2.0 (95% CI, 1.2 to 3.2; P trend=0.005). After adjustment for lipid and nonlipid risk factors, including C-reactive protein, tPA antigen remained a significant predictor. Multivariable-adjusted associations for D-dimer, although attenuated, largely remained statistically significant. When stratified by HT, the relationship between tPA antigen and incident coronary heart disease was similar among nonusers, estrogen-only users, and current users of any HT.Elevated tPA antigen and, to a lesser extent, D-dimer are independently associated with incident coronary events among postmenopausal women. In analyses stratified by HT, tPA antigen remained a consistent marker of increased coronary risk.
Publication
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Baseline associations between post and inflammatory, haemostatic, and lipid biomarkers of coronary heart disease. The Women's Health Initiative Observational StudyRobert Langer
Langer RD, Pradhan AD, Lewis CE, Manson JE, Rossouw JE, Hendrix SL, LaCroix AZ, Ridker PM. Baseline associations between postmenopausal hormone therapy and inflammatory, haemostatic, and lipid biomarkers of coronary heart disease. The Women's Health Initiative Observational Study. Thromb Haemost. 2005 Jun;93(6):1108-16.
thrombosis, inflammation, biomarkers, coronary heart disease, myocardial infarctionObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15968396https://www.whi.org/researchers/bibliography/Manuscripts/ms130.pdf
Clinical trials of postmenopausal hormone therapy (PHT) have found an early increase in cardiovascular events, and have not demonstrated the reduction in coronary heart disease (CHD) predicted from changes in conventional risk factors or found in observational studies, suggesting that PHT may increase coronary risk through other pathways. We compared baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), sICAM-1, tissue plasminogen activator antigen (tPA-antigen), D-dimer, homocysteine, triglycerides, total-, HDL- and LDL- cholesterol in 304 cases with incident CHD and 304 controls, according to self-reported use of PHT. Subjects were selected from the 75,343 participants in the WHI Observational Study without baseline cardiovascular disease or cancer. PHT was associated with higher CRP, HDL and triglycerides, and lower tPA-antigen and homocysteine. CRP was highest in users of unopposed conjugated equine estrogen. Levels of IL-6,sICAM-1,D-dimer and total cholesterol did not differ between PHT users and non-users. Transdermal estrogen users had low levels of D-dimer and CRP. Among users of estrogen plus progestin (EP), CRP, IL-6, tPA-antigen, D-dimer, total cholesterol and triglycerides were higher in women with incident coronary events than controls. Estrogen alone (E) controls shared only the tPA-antigen association, but had higher HDL and lower LDL than E cases. In non-users CRP, tPA-antigen and D-dimer were associated with incident CHD. In summary, risk markers differed by PHT category. Some associations differed between women with and without incident CHD, especially for EP, where inflammatory and thrombotic markers were higher in cases. These associations remain speculative pending confirmation in randomized trials.
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Association of nonmelanoma skin cancer with second malignancyCarol Rosenberg
Rosenberg CA, Greenland P, Khandekar J, Loar A, Ascensao J, Lopez AM. Association of nonmelanoma skin cancer with second malignancy. Cancer. 2004 Jan 1;100(1):130-8.
non-melanoma skin cancer, second malignancyBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14692033https://www.whi.org/researchers/bibliography/Manuscripts/ms132.pdf
Heightened risks of second cancers have been reported in patients with nonmelanoma cancer of the skin (NMSC), but this association has not been studied in a large, ethnically diverse, multigeographic population.This cross-sectional study assessed the association of NMSC with another malignancy in the Women's Health Initiative Observational Study, a study that was conducted in 40 communities throughout the U.S. and involved 93,676 postmenopausal women ages 50-79 years. Cancer history, demographics, and previous and current risk exposures were determined by questionnaire at a baseline examination. Logistic regression was used to assess the association (odds ratio) of a history of NMSC with a history of other (non-NMSC) cancers controlling for age and potential confounding factors. Complete cancer data were available in 92,658 women.In age-adjusted analyses, women with a history of NMSC (n = 7554 women) were 2.30 times as likely to report a history of another cancer, other than NMSC, compared with women who had no history of NMSC (95% confidence interval [95% CI], 2.18-2.44). In a subgroup analysis, black women with NMSC had 7.46 times the odds (95% CI, 3.08-18.0) of reporting a second malignancy compared with black women without NMSC.This study provides additional evidence of an association between NMSC and another malignancy in a large, multiethnic population.
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Additional self-monitoring tools in the dietary modification component of the Women's Health InitiativeYasmin Mossavar-Rahmani
Mossavar-Rahmani Y, Henry H, Rodabough R, Bragg C, Brewer A, Freed T, Kinzel L, Pedersen M, Soule CO, Vosburg S. Additional self-monitoring tools in the dietary modification component of the Women's Health Initiative. J Am Diet Assoc. 2004 Jan;104(1):76-85.
self-monitoring, food diaries, adherenceClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/14702588https://www.whi.org/researchers/bibliography/Manuscripts/ms134.pdf
Self-monitoring promotes behavior changes by promoting awareness of eating habits and creates self-efficacy. It is an important component of the Women's Health Initiative dietary intervention. During the first year of intervention, 74% of the total sample of 19,542 dietary intervention participants self-monitored. As the study progressed the self-monitoring rate declined to 59% by spring 2000. Participants were challenged by inability to accurately estimate fat content of restaurant foods and the inconvenience of carrying bulky self-monitoring tools. In 1996, a Self-Monitoring Working Group was organized to develop additional self-monitoring options that were responsive to participant needs. This article describes the original and additional self-monitoring tools and trends in tool use over time. Original tools were the Food Diary and Fat Scan. Additional tools include the Keeping Track of Goals, Quick Scan, Picture Tracker, and Eating Pattern Changes instruments. The additional tools were used by the majority of participants (5,353 of 10,260 or 52% of participants who were self-monitoring) by spring 2000. Developing self-monitoring tools that are responsive to participant needs increases the likelihood that self-monitoring can enhance dietary reporting adherence, especially in long-term clinical trials.
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135
Radiographic measurements, bone mineral density, and the Singh Index in the proximal femur of white and black postmenopausal womenDavid Barondess
Barondess DA, Singh M, Hendrix SL, Nelson DA. Radiographic measurements, bone mineral density, and the Singh Index in the proximal femur of white and black postmenopausal women. Dis Mon. 2002 Oct;48(10):637-46.
Singh Index, bone mineral density, ethnic differences, hip X-rays, ancillary studyBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12562051https://www.whi.org/researchers/bibliography/Manuscripts/ms135.pdf
Radiographic measurements, bone mineral density (BMD), and the Singh Index were examined to assess ethnic differences in the architecture and trabecular patterns in the proximal femur.We measured height (cm), weight (kg), and the following radiographic variables in 326 white and black postmenopausal women participating in the Women's Health Initiative at the Clinical Center in Detroit, MI: neck breadth, inferior neck cortical thickness, head diameter, subtrochanteric breadth, and subtrochanteric medial and lateral cortical thicknesses. Bone densitometry was performed by dual-energy x-ray absorptiometry (Hologic QDR 1000 plus; Hologic Inc, Bedford, MA) at 5 regional sites in the proximal femur. The Singh Index was read by its originator.There was no significant ethnic difference in mean age, height, or body mass index, but weight and BMD was higher in the black group at all regional sites. The inferior neck cortical thickness was significantly greater in the black group. The Singh Index was found to be grade VI (normal) in 87%, grade V in 9%, and grades II-IV in 4% of all subjects. Multiple regression models explained 35% to 60% of the variance in the regional BMDs; the Singh Index, weight, and subtrochanteric cortical thicknesses were significant contributors to all regional hip BMD models. Although there were ethnic differences in BMD, there were no ethnic differences in the distribution of the Singh Index scores.
Publication
137
Recruitment of hispanic women to the Women's Health Initiative: The case of Embajadoras in ArizonaLinda Larkey
Larkey LK, Staten LK, Ritenbaugh C, Hall RA, Buller DB, Bassford T, Altimari BR. Recruitment of hispanic women to the Women's Health Initiative. The case of Embajadoras in Arizona. Control Clin Trials. 2002;23(3):289-298
Hispanic health, minority recruitment, clinical trials, ancillary studyBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12057880https://www.whi.org/researchers/bibliography/Manuscripts/ms137.pdf
This study examined the use of lay advocates (i.e., women enrolled in a study who advocate to others) to improve recruitment among Hispanic women in the Arizona recruitment sites for a large-scale, national prevention study, the Women's Health Initiative (WHI). We examined whether trained, Hispanic lay advocates (called Embajadoras) brought more women into the study than a matched group of Hispanic and Anglo enrollees in the WHI who were supplied with brochures. Fifty-six Hispanic participants in the WHI were randomized to receive training or no training on advocacy, and continued to meet quarterly for 18 months. Also, 42 Anglo women were assigned to control. All groups received brochures to use for advocating the WHI. The number of women referred and enrolled was tracked as well as other factors expected to influence outcomes. Embajadoras were more successful at referral and enrollment than untrained Hispanic women and more successful at enrollment than untrained Anglo controls. Embajadoras were also found to distribute significantly more brochures than control groups. Therefore, a culturally aligned training program to encourage current Hispanic participants in a clinical trial to advocate the study to others may be an effective way to boost referrals and enrollments. Other potential influences on enrollment or referral success could not be determined due to the small sample size. Further study is needed to examine the best methods to encourage enrollment for women referred to the study.
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Baseline experience with Modified Mini Mental State Exam: The Women's Health Initiative Memory Study (WHIMS)Steve Rapp
Rapp SR, Espeland MA, Hogan P, Jones BN, Dugan E, The WHIMS investigators. Baseline experience with Modified Mini Mental State Exam: The Women's Health Initiative Memory Study (WHIMS). Aging Ment Health. 2003 May;7(3):217-23.
cognition, 3MS, MMSE, psychometrics, normative , WHIMSMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12775404https://www.whi.org/researchers/bibliography/Manuscripts/ms138.pdf
AS39
The Modified Mini Mental State Exam (3MS) is widely used for screening global cognitive functioning, however little is known about its performance in clinical trials. We report the distribution of 3MS scores among women enrolled in the Women's Health Initiative Memory Study (WHIMS) and describe differences in these scores associated with age, education, and ethnicity. The 3MS exams were administered to 7,480 women aged 65-80 who had volunteered for and were eligible for a clinical trial on postmenopausal hormone therapy. General linear models were used to describe demographic differences among scores. Factor analysis was used to characterize the correlational structure of exam subscales.The distribution of 3MS scores at baseline was compressed in WHIMS compared to population-based data. Mean 3MS scores (overall 95.1) tended to decrease with age and increase with education, however these associations varied among ethnic groups (p< 0.0001) even after adjustment for health, physical disability and occupation attainment. Four factors accounted for 37% of the total variance. Each varied with education and ethnicity; the two most prominent factors also varied with age. Despite relatively narrow distributions in WHIMS, baseline 3MS scores retained associations with age and education. These associations varied among ethnic groups, so that care must be taken in comparing data across populations.
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139
Cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase activities in hispanic and anglo postmenopausal women: Associations with total and regional body fatKathryn Greaves
Greaves KA, Going SB, Fernandez ML, Milliken LA, Lohman TG, Bassford T, McNamara DJ. Cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase activities in hispanic and anglo postmenopausal women: Associations with total and regional body fat. Metabolism. 2003 Mar;52(3):282-9.
cholesterol, racial/ethnic differencesObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12647264https://www.whi.org/researchers/bibliography/Manuscripts/ms139.pdf
Reverse cholesterol transport is one process by which high-density lipoprotein (HDL) cholesterol has been hypothesized to play a role in reducing the risk of coronary heart disease. This study was designed to examine cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) activities, 2 modulators of reverse cholesterol transport, in Hispanic and Anglo postmenopausal women. The associations between plasma CETP and LCAT activities and body composition were also examined. Of the 199 subjects, 33% were of Hispanic origin and 47% were undergoing hormone replacement therapy (HRT). Body composition was measured by dual-energy x-ray absorptiometry (DXA) and anthropometry. Plasma CETP activity was higher in Hispanic compared to Anglo women, although the difference was eliminated when data were adjusted for abdominal fat. Hispanic women had lower plasma HDL cholesterol concentrations, higher total cholesterol:HDL cholesterol ratios and triglyceride concentrations, and greater susceptibility of low-density lipoprotein (LDL) particles to oxidation. Hispanic women also had a significantly greater relative deposition of body fat on the trunk and intra-abdominally than did Anglo women, even after adjusting for total body fat. There were no significant ethnic differences in LCAT activity. Plasma CETP and LCAT activities were negatively correlated with HDL cholesterol and positively correlated with total cholesterol, LDL cholesterol, and triglycerides, as well as total and regional body composition variables. In conclusion, results suggest a greater risk for coronary heart disease in Hispanic women compared to Anglo women.
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Usefulness of prior hysterectomy as an independent predictor of Framingham risk score (The Women's Health Initiative)Judith Hsia
Hsia J, Barad D, Margolis K, Rodabough R, McGovern PG, Limacher MC, Oberman A, Smoller S, Women's Health Initiative Research Group. Usefulness of prior hysterectomy as an independent predictor of Framingham risk score (The Women's Health Initiative). Am J Cardiol. 2003 Aug 1;92(3):264-9.
cardiac risk, hysterectomy, hormone replacement, estrogen, Progestin, FraminghamBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12888128https://www.whi.org/researchers/bibliography/Manuscripts/ms140.pdf
The association of hysterectomy with increased coronary risk is controversial, and previous studies have reached differing conclusions as to whether the excess risk is confined to women who have also undergone bilateral oophorectomy. This analysis uses the Framingham algorithm to evaluate the hypothesis that hysterectomy with or without ovarian preservation is associated with increased coronary risk, using a cross-sectional analysis of baseline data from 1,501 participants of the Women's Health Initiative. Framingham risk scores, derived from the algorithm in the National Cholesterol Education Program Adult Treatment Panel III guidelines, which include age, smoking, systolic blood pressure, total and high-density lipoprotein cholesterol, were determined in a subgroup of Women's Health Initiative participants with measured plasma lipids and known ovariectomy status. Women with hysterectomy had fewer years of education than those without hysterectomy (30% with college degree vs 41%, p <0.0001) and higher body mass index (29 vs 28 kg/m(2), p <0.0001), consumed less alcohol, exercised less, and had a higher Framingham risk of myocardial infarction or coronary death (46% vs 41% with 10-year risk >/=4%, p = 0.04). In multivariate analysis, hysterectomy with bilateral oophorectomy was an independent predictor of Framingham risk (p = 0.04), whereas hysterectomy with ovarian preservation was not.
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Coronary artery calcification in black women and white womenCharanjit Khurana
Khurana C, Rosenbaum CG, Howard BV, Adams-Campbell LL, Detrano RC, Klouj A, Hsia J. Coronary artery calcification in black women and white women. Am Heart J. 2003 Apr;145(4):724-9.
coronary calcium scores, ethnicity, ancillary studyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12679771https://www.whi.org/researchers/bibliography/Manuscripts/ms142.pdf
Coronary calcification is a potent independent predictor of coronary risk. Sex-specific risk categories based on calcium scores have been established, but ethnic differences in coronary calcification have been little studied. This prospective cohort study compares coronary calcification, assessed by computed tomography, in postmenopausal black women and white women.Computed tomographic scans were performed on 128 black women and 733 white women without known coronary artery disease (mean age 63 +/- 8 years). Although coronary risk factors were more prevalent among black women (P <.0001), total calcium scores were similar to those in white women. By use of the Framingham algorithm, higher calcium scores were associated with higher 10-year risk of myocardial infarction or coronary death. In multiple regression analysis, age was independently associated with higher calcium scores in both ethnic groups (P =.002 for black women, P <.0001 for white women). Diabetes mellitus and not exercising at least 3 times per week were independently associated with higher calcium scores in white women but not black women. Educational level, body mass index, current hormone replacement therapy, hysterectomy, dietary fat consumption, family history of premature coronary disease, hypertension, self-reported high cholesterol, and current smoking were not independently associated with coronary calcium score in black women, white women, or the combined cohort; neither was ethnicity an independent predictor of coronary calcification.Despite higher dietary fat consumption, higher body mass index, and greater prevalence of hypertension, diabetes, and smoking, black women had coronary calcium scores similar to those of white women. Ethnicity was not an independent predictor of coronary calcification.
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Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy: The Women's Health Initiative Observational StudyBarbara Howard
Howard BV, Kuller L, Langer R, Manson JE, Allen C, Assaf A, Cochrane BB, Larson JC, Lasser N, Rainford M, Van Horn L, Stefanick ML, Trevisan M. Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy: The Women's Health Initiative Observational Study. Circulation. 2005 Mar 29;111(12):1462-70. Epub 2005 Mar 21.
hormone replacement therapy, mortality, morbidity, epidemiology, cardiovascular diseaseObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15781742https://www.whi.org/researchers/bibliography/Manuscripts/ms144.pdf
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in women and may vary by hysterectomy (or oophorectomy) status. This study compared CVD risk factors and rates between postmenopausal women who had and had not undergone hysterectomy, with or without oophorectomy.This analysis was conducted on 89 914 women in the Women's Health Initiative (WHI) Observational Study. Participants reported demographic characteristics, medical history, dietary habits, physical activity, medications, and previous hysterectomy (with or without oophorectomy). Baseline weight, height, waist circumference, and blood pressure were measured. CVD events were ascertained during 5.1 years of mean follow-up and adjudicated with standard criteria. Black, Hispanic, and American Indian women had higher rates of hysterectomy than white women (52.9%, 44.6%, and 49.2% versus 40.0%, respectively), and Asian/Pacific Islander women had lower rates (33.8%). Women with a hysterectomy (regardless of oophorectomy status) had an adverse risk profile at baseline compared with women with no hysterectomy, including a higher proportion of hypertension, diabetes, high cholesterol, obesity, and lower education, income, and physical activity (all P<0.01). Total mortality and fatal and nonfatal CVD were higher among women with a hysterectomy. Hysterectomy (regardless of oophorectomy status) was a significant predictor of CVD (HR: 1.26, P<0.001). After adjustment for demographic variables and CVD risk factors, the effect was reduced and nonsignificant.Women with a hysterectomy had a worse risk profile and higher prevalence and incidence of CVD in this cohort. Multivariate models suggest that hysterectomy is not the major determinant of this outcome; rather, CVD risk may be due to the more adverse initial risk profile of women who had undergone hysterectomy.
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145
Breast cancer and nonsteroidal anti-inflammatory drugs: Prospective results from the Women's Health InitiativeRandall Harris
Harris RE, Chlebowski RT, Jackson RD, Frid DJ, Ascenseo JL, Anderson G, Loar A, Rodabough RJ, White E, McTiernan A. Breast cancer and nonsteroidal anti-inflammatory drugs: Prospective results from the Women's Health Initiative. Cancer Res. 2003 Sep 15;63(18):6096-101.
NSAIDS, breast cancerObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/14522941https://www.whi.org/researchers/bibliography/Manuscripts/ms145.pdf
We analyzed data from the prospective Women's Health Initiative (WHI) Observational Study to examine the effects of regular use of aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer risk. We studied a population of 80,741 postmenopausal women between 50 and 79 years of age who reported no history of breast cancer or other cancers (excluding nonmelanoma skin cancer), and we completed a personal baseline interview that elicited comprehensive health information including data on breast cancer risk factors and NSAID use. All of the cases were adjudicated by WHI physicians using pathology reports. Our analysis was based on 1392 confirmed cases of breast cancer. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated with adjustment for age and other breast cancer risk factors. Regular NSAID use (two or more tablets/week) for 5-9 years produced a 21% reduction in the incidence of breast cancer (RR, 0.79; 95% CI, 0.60-1.04); regular NSAID use for 10 or more years produced a 28% reduction (RR, 0.72; CI, 0.56-0.91), and there was a statistically significant inverse linear trend of breast cancer incidence with the duration of NSAID use (P < 0.01). The estimated risk reduction for long-term use of ibuprofen (RR, 0.51; CI, 0.28-0.96) was greater than for aspirin (RR, 0.79; CI, 0.60-1.03). Subgroup analysis by breast cancer risk factors did not result in effect modification. Regular use of acetaminophen (an analgesic agent with little or no anti-inflammatory activity) or low-dose aspirin (<100 mg) was unrelated to the incidence of breast cancer. Our results indicate that the regular use of aspirin, ibuprofen, or other NSAIDs may have a significant chemopreventive effect against the development of breast cancer and underscore the need for clinical trials to confirm this effect.
Approved Manuscript
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Selected risk factors and dietary intake differences in postmenopausal African American and caucasian women with coronary heart diseaseFlorenzia Davis
CHD, risk factors, dietary intakeBoth OS and CT
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148
Incidence of cervical cytological abnormalities with aging in the Women's Health Initiative: A randomized controlled trialShagufta Yasmeen
Yasmeen S, Romano PS, Pettinger M, Johnson SR, Hubbell FA, Lane DS, Hendrix SL. Incidence of cervical cytological abnormalities with aging in the Women's Health Initiative: A randomized controlled trial. Obstet Gynecol. 2006 Aug;108(2):410-9.
cervical cytologic abnormalities, pap smears, cervical cancer risk factorsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16880313https://www.whi.org/researchers/bibliography/Manuscripts/ms148.pdf
To estimate the incidence of cytological abnormalities and cervical cancer and to determine the effect of oral estrogen and progestin on cervical cytology among postmenopausal women participating in a multi-institution clinical trial.The study was a longitudinal analysis of a prospective cohort of 16,608 postmenopausal women (aged 50-79 years) participating in the Women's Health Initiative (WHI) clinical trial of estrogen plus progestin. Eligible participants had a cervical smear within 1 year before randomization and at 3- and 6-year follow-ups. Outcomes measured were low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical cancer at follow-up years 3 and 6.Of 15,733 eligible participants with a uterus, 7,663 were assigned to placebo and 8,070 to estrogen plus progestin. At baseline, 318 women (2%) had low-grade abnormalities on cervical cytology. The annual incidence rate of any new cytological abnormality in the estrogen plus progestin group was significantly higher than that in the placebo group (hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.6). Independent risk factors for HSIL and cervical cancer over a 6-year follow-up (after stratifying for baseline cytologic abnormalities) included sexual activity in the past year while not being married or living as married (hazard ratio 3.5, 95% CI 1.5-8.3). Risk factors did not include age or use of estrogen plus progestin.Use of estrogen plus progestin was associated with increased incidence of any cytologic abnormality, although it had no impact on the incidence of HSIL or cervical cancer. Sexually active older women who are not married or living as married may benefit from continued cervical cancer screening.Clinicaltrials.gov, www.clinicaltrials.gov, NCT00000611.
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A community-based study of postmenopausal white women with back and leg pain: Health status and limitations in physical activityMolly Vogt
Vogt MT, Lauerman WC, Chirumbole M, Kuller LH. A community-based study of postmenopausal white women with back and leg pain: Health status and limitations in physical activity. J Gerontol A Biol Sci Med Sci. 2002 Aug;57(8):M544-50.
prevalence, lumbar stenosis, health status and functioningObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/12145370https://www.whi.org/researchers/bibliography/Manuscripts/ms149.pdf
The objective of this study was to determine the prevalence of lower back pain and associated leg pain/numbness in postmenopausal Caucasian women and the relationship of these symptoms to health status and function.A convenience sample of 573 white women enrolled in the Observational Study of the Women's Health Initiative (WHI) in Pittsburgh completed a questionnaire on low back pain (LBP) and leg pain (LP) and its impact on their daily activity. For data analysis, this information was merged with that obtained under the standard WHI protocol.Almost half of the women (49%) reported having had LBP during the previous month: 8% had LBP only, while 41% had both LBP and LP. In 9% of women, the leg and back symptoms were alleviated by sitting. Among women with LBP during the previous month, those who also had leg pain were five times more likely to have had functional limitations, two to four times more likely to have consulted a clinician or taken medications, and more likely to have had prior spinal surgery or hospitalization than the women with no LP. Based on the Short Form-36, women with LBP/LP had significantly lower scores for physical function, physical role, and bodily pain than women with no LBP or with LBP alone.Low back pain that radiates into the hip, buttock, or leg is relatively common in postmenopausal Caucasian women living in the community and is associated with decreased physical health status and with physical limitations.
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152
Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational StudyTanya Orchard
Orchard TS, Larson JC, Alghothani N, Bout-Tabaku S, Cauley JA, Chen Z, Lacroix AZ, Wactawski-Wende J, Jackson RD. Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study. Am J Clin Nutr. 2014 Apr;99(4):926-33. doi: 10.3945/ajcn.113.067488. Epub 2014 Feb 5
magnesium, fracture riskObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/24500155https://www.whi.org/researchers/bibliography/Manuscripts/Ms152.pdf
Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear.We examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD).This prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants.Baseline hip BMD was 3% higher (P < 0.001), and whole-body BMD was 2% higher (P < 0.001), in women who consumed >422.5 compared with <206.5 mg Mg/d. However, the incidence and RR of hip and total fractures did not differ across quintiles of magnesium. In contrast, risk of lower-arm or wrist fractures increased with higher magnesium intake [multivariate-adjusted HRs of 1.15 (95% CI: 1.01, 1.32) and 1.23 (95% CI: 1.07, 1.42) for quintiles 4 and 5, respectively, compared with quintile 1; P-trend = 0.002]. In addition, women with the highest magnesium intakes were more physically active and at increased risk of falls [HR for quintile 4: 1.11 (95% CI: 1.06, 1.16); HR for quintile 5: 1.15 (95% CI: 1.10, 1.20); P-trend < 0.001].Lower magnesium intake is associated with lower BMD of the hip and whole body, but this result does not translate into increased risk of fractures. A magnesium consumption slightly greater than the Recommended Dietary Allowance is associated with increased lower-arm and wrist fractures that are possibly related to more physical activity and falls.
Publication
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Cynicism: incident diabetes and worsening of metabolic syndrome in postmenopausal womenJudith Wylie-Rosette
Wylie-Rosetta J, Aragaki AK, Cochrane B, Perri MG, Rosal MC and Rapp SR. Cynicism: incident diabetes and worsening of metabolic syndrome in postmenopausal women. Diabetes Metab Syndr: Clin Res & Rev. 2010 Oct-Dec;(4):187–189
diabetes, depression, metabolic syndrome, mood, obesity, glucose, CVD riskClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/25663951https://www.whi.org/researchers/bibliography/Manuscripts/ms153.pdf
OBJECTIVE: To determine if self-reported cynical hostility predicted incident diabetes or increase in number of symptoms associated with metabolic syndrome in postmenopausal women. DESIGN: Prospective study of a subsample of women (n = 3,658) participating in the Women's Health Initiative Clinical Trial. METHODS: Subjects: Postmenopausal women aged 50 to 79 years at baseline who were enrolled in the Women's Health Initiative Dietary Modification Trial, Hormone Trial or both. Measures: The Cynicism subscale of the Cook-Medley Hostility Questionnaire was used to assess cynical hostility at baseline. Incident diabetes was ascertained by self-report of treatment with insulin or oral hypoglycemic medication at one year. Metabolic syndrome was defined based on number of Adult Treatment Panel (ATP) III criteria met at one year. Statistical Analysis: The relationship between baseline cynical hostility and incident diabetes and worsening of metabolic syndrome was assessed from baseline to one year using multivariable Cox proportional hazards models and multivariable logistic regression models, respectively. RESULTS: Incident diabetes was 36% higher among women in the upper tertile for baseline cynical hostility compared to the lowest tertile (p-trend = 0.05). The odds of a worsening of metabolic syndrome was 27% greater in the highest cynical hostility tertile compared to the lowest tertile (p-trend = 0.04). CONCLUSIONS: Cynical hostility may increase the risk for developing diabetes and worsening of the metabolic syndrome in postmenopausal women.
Publication
155
Changes in food sources of dietary fat in response to an intensive low-fat dietary intervention: Early results from the Women’s Health InitiativeRuth Patterson
Patterson RE, Kristal A, Rodabough R, Caan B, Lillington L, Mossavar-Rahmani Y, Simon MS, Snetselaar L, Van Horn L. Changes in food sources of dietary fat in response to an intensive low-fat dietary intervention: Early results from the Women's Health Initiative. J Am Diet Assoc. 2003 Apr;103(4):454-60.
dietary fat, food consumption, low-fat interventionClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12669007https://www.whi.org/researchers/bibliography/Manuscripts/ms155.pdf
To evaluate changes in food sources of dietary fat made by participants in the Women's Health Initiative Low-Fat Dietary Modification Trial.This study compares sources of dietary fat intake, estimated by a food frequency questionnaire, between intervention and control participants at baseline, 1 year (year 1) and 2 years (year 2) after randomization. The outcome measure was intake of fat in grams per day. Results are given on consumption of fat from six food groups and the intervention effect, defined as mean change in the intervention group minus the change in controls, controlling for baseline fat intake.5,004 intervention and 7,426 control postmenopausal women in 40 clinical centers across the United States.At baseline, the major sources of fat were added fats, such as butter, oils, and salad dressings (25%); meats (21%); and desserts (13%). From baseline to year 1, the intervention group reduced fat by 24.3 g/day compared with the control group. Reductions came primarily from added fats (9.1 g/day), meats (4.6 g/day), and desserts (3.9 g/day). White people reduced added fats more than other race/ethnicity groups did, white and Hispanic people were more likely to reduce fat intake from milk and cheese compared with other groups, and Hispanics reduced fat from mixed dishes more than did other race/ethnicity groups (P<.05 for all).These data indicate that women in the Women's Health Initiative dietary change intervention made substantial changes in food choices. These results can facilitate future low-fat interventions, and also offer clinical applications, by identifying foods that may be refractory to change.
Approved Manuscript
158
Participants' response to the release of preliminary information on cardiovascular disease events from the WHI hormone trialErin O'Fallon
estrogen, progesterone, hormone replacement therapy, adverse effects, cardiovascular disease, informed consentClinical Trial
Publication
163
Ethnicity and breast cancer: Factors influencing differences in incidence and outcomeRowan Chlebowski
Chlebowski RT, Chen Z, Anderson GL, Rohan T, Aragaki A, Lane D, Dolan NC, Paskett ED, McTiernan A, Hubbell FA, Adams-Campbell LL, Prentice R. Ethnicity and breast cancer: Factors influencing differences in incidence and outcome. J Natl Cancer Inst. 2005 Mar 16;97(6):439-48.
ethnic differences, breast cancer, incidence ratesObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15770008https://www.whi.org/researchers/bibliography/Manuscripts/ms163.pdf
The lower breast cancer incidence in minority women and the higher breast cancer mortality in African American women than in white women are largely unexplained. The influence of breast cancer risk factors on these differences has received little attention.Racial/ethnic differences in breast cancer incidence and outcome were examined in 156,570 postmenopausal women participating in the Women's Health Initiative. Detailed information on breast cancer risk factors including mammography was collected, and participants were followed prospectively for breast cancer incidence, pathological breast cancer characteristics, and breast cancer mortality. Comparisons of breast cancer incidence and mortality across racial/ethnic groups were estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazard models. Tumor characteristics were compared as odds ratios (ORs) and 95% confidence intervals in logistic regression models.After median follow-up of 6.3 years, 3938 breast cancers were diagnosed. Age-adjusted incidences for all minority groups (i.e., African American, Hispanic, American Indian/Alaskan Native, and Asian/Pacific Islander) were lower than for white women, but adjustment for breast cancer risk factors accounted for the differences for all but African Americans (HR = 0.75, 95% CI = 0.61 to 0.92) corresponding to 29 cases and 44 cases per 10,000 person years for African American and white women, respectively. Breast cancers in African American women had unfavorable characteristics; 32% of those in African Americans but only 10% in whites were both high grade and estrogen receptor negative (adjusted OR = 4.70, 95% CI = 3.12 to 7.09). Moreover, after adjustment for prognostic factors, African American women had higher mortality after breast cancer than white women (HR = 1.79, 95% CI = 1.05 to 3.05) corresponding to nine and six deaths per 10 000 person-years from diagnosis in African American and white women, respectively.Differences in breast cancer incidence rates between most racial/ethnic groups were largely explained by risk factor distribution except in African Americans. However, breast cancers in African American women more commonly had characteristics of poor prognosis, which may contribute to their increased mortality after diagnosis.
Publication
164
Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: The Women's Health Initiative Observational StudyKaren Margolis
Margolis KL, Manson JE, Greenland P, Rodabough RJ, Bray PF, Safford M, Grimm RH,Jr, Howard BV, Assaf AR, Prentice R, Women's Health Initiative Research Group. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: The Women's Health Initiative Observational Study.  Arch Intern Med. 2005 Mar 14;165(5):500-8.
leukocyte count, cardiovascular diseases, coronary diseases, cerebrovascular disordersObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15767524https://www.whi.org/researchers/bibliography/Manuscripts/ms164.pdf
Increasing evidence supports a role for inflammation in the atherosclerotic process. The role of the leukocyte count as an independent predictor of risk of a first cardiovascular disease (CVD) event remains uncertain. Our objective was to describe the relation between the baseline white blood cell (WBC) count and future CVD events and mortality in postmenopausal women.In this prospective cohort study set in 40 US clinical centers, the study population comprised 72 242 postmenopausal women aged 50 to 79 years, free of CVD and cancer at baseline, enrolled in the Women's Health Initiative Observational Study. Main outcome measures included incident fatal coronary heart disease (CHD), nonfatal myocardial infarction, stroke, and total mortality.At baseline, the mean +/- SD age of the women was 63 +/- 7.3 years, 84% were white, 4% had diabetes, 35% had hypertension, and 6% were current smokers. The mean WBC count was 5.8 +/- 1.6 x 10(9) cells/L. During a mean of 6.1 years of follow-up, there were 187 CHD deaths, 701 nonfatal myocardial infarctions, 738 strokes, and 1919 deaths from all causes. Compared with women with WBC counts in the first quartile (2.5-4.7 x 10(9) cells/L), women in the fourth quartile (6.7-15.0 x 10(9) cells/L) had over a 2-fold elevated risk for CHD death (hazard ratio, 2.36; 95% confidence interval, 1.51-3.68), after multivariable adjustment for age, race, diabetes, hypertension, smoking, hypercholesterolemia, body mass index, alcohol intake, diet, physical activity, aspirin use, and hormone use. Women in the upper quartile of the WBC count also had a 40% higher risk for nonfatal myocardial infarction, a 46% higher risk for stroke, and a 50% higher risk for total mortality. In multivariable models adjusting for C-reactive protein, the WBC count was an independent predictor of CHD risk, comparable in magnitude to C-reactive protein.The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.
Approved Manuscript
165
Comparison of health behaviors by breast cancer statusMarilyn Johnson Kozlow
breast cancer, health behaviors, physical activity, lifestyle behaviors, womenObservational Study
Publication
166
Habitual tea consumption and risk of osteoporosis: A prospective study in the Women's Health Initiative observational cohortZhao Chen
Chen Z, Pettinger MB, Ritenbaugh C, LaCroix AZ, Robbins J, Caan BJ, Barad DH, Hakim IA. Habitual tea consumption and risk of osteoporosis: A prospective study in the Women's Health Initiative observational cohort. Am J Epidemiol. 2003 Oct 15;158(8):772-81.
tea consumption, osteoporotic fractures, BMD, bone lossObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/14561667https://www.whi.org/researchers/bibliography/Manuscripts/ms166.pdf
The purpose of this study was to prospectively investigate associations of habitual drinking of regular tea with bone mineral density and fracture risk. Study participants were a multiethnic postmenopausal cohort (n = 91,465) from the nationwide Women's Health Initiative Observational Study. These women were recruited in the United States and aged 50-79 years at the time of enrollment (1994-1998). The average follow-up time was 4.1 years. Habitual consumption of regular tea was assessed with a structured questionnaire at baseline. Clinical fractures during the follow-up were reported in questionnaires, and hip fractures were further confirmed by reviewing medical records. Bone mineral density measurements were conducted among a subgroup of women (n = 4,979) at three Women's Health Initiative bone mineral density centers using dual-energy x-ray absorptiometry. Multivariate analyses suggested a positive trend of increased total body bone mineral density with tea drinking (p < 0.05). However, results from the Cox proportional hazard models did not show any significant association between tea drinking and the risk of fractures at the hip and forearm/wrist. In conclusion, the results from this study indicate that the effect of habitual tea drinking on bone density is small and does not significantly alter the risk of fractures among the US postmenopausal population.
Approved Manuscript
167
Factors associated with participation in the Women's Health Initiative clinical trial at the Western New York Vanguard Clinical CenterCheryl Klemenz
demographic differences,Clinical Trial
Publication
169
Reliability and validity of the Women's Health Initiative Insomnia Rating ScaleDouglas Levine
Levine DW, Kripke DF, Kaplan RM, Lewis MA, Naughton MJ, Bowen DJ, Shumaker SA. Reliability and validity of the Women's Health Initiative Insomnia Rating Scale. Psychol Assess. 2003 Jun;15(2):137-48.
insomnia ratingBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/12847774https://www.whi.org/researchers/bibliography/Manuscripts/ms169.pdf
The reliability and construct validity of the 5-item Women's Health Initiative Insomnia Rating Scale (WHIIRS) were evaluated in 2 studies. In Study 1, using a sample of 66,269 postmenopausal women, validity of the WHIIRS was assessed by examining its relationship to other measures known to be related to sleep quality. Reliability of the WHIIRS was estimated using a resampling approach; the mean alpha coefficient was .78. Test-retest reliability coefficients were .96 for same-day administration and .66 after a year or more. Correlations of the WHIIRS with the other measures were in the predicted directions. Study 2 used a sample of 459 women and compared the WHIIRS with objective indicators of sleep quality. Results showed that differences in the objective indicators could be detected by the WHIIRS. Findings suggest that a between-group mean difference of approximately 0.50 of a standard deviation on the WHIIRS may be clinically meaningful.
Publication
171
Prevalence and correlates of panic attacks in postmenopausal women: Results from an ancillary study to the Women’s Health InitiativeJordan Smoller
Smoller JW, Pollack MH, Wassertheil-Smoller S, Barton B, Hendrix SL, Jackson RD, Dicken T, Oberman A, Sheps DS, Women's Health Initiative Investigators. Prevalence and correlates of panic attacks in postmenopausal women: Results from an ancillary study to the Women's Health Initiative. Arch Intern Med. 2003 Sep 22;163(17):2041-50.
prevalence, correlates, panic attacksBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14504117https://www.whi.org/researchers/bibliography/Manuscripts/ms171.pdf
AS70
Panic attacks are known to be more common in women than in men, but the prevalence and correlates of panic in the postmenopausal period have not been well defined.Cross-sectional survey of 3369 community-dwelling postmenopausal women enrolled between December 1, 1997, and November 30, 2000, in the Myocardial Ischemia and Migraine Study, a 10-center ancillary study of the 40-center Women's Health Initiative. Participants, aged 50 to 79 years and predominantly white (73%), completed questionnaires about the occurrence of panic attacks in the previous 6 months and about migraine headaches and underwent 24-hour ambulatory electrocardiographic monitoring. The 6-month prevalences of full-blown and limited-symptom panic attacks were calculated, and their associations with other sociodemographic and clinical variables were examined in multivariate analyses.One of the panic attack types was reported by 17.9% (95% confidence interval, 16.6%-19.2%) of women (full-blown attacks, 9.8%; limited-symptom attacks, 8.1%). Adjusting for age and race or ethnicity, full-blown panic attacks were more common in women with a history of migraine, emphysema, cardiovascular disease, chest pain during ambulatory electrocardiography, and symptoms of depression. Full-blown panic attacks were associated in a dose-response manner with negative life events during the past year. Panic attacks were associated with functional impairment even after adjusting for comorbid medical conditions and depression. There was no significant association with self-reported use of hormone replacement therapy.Panic attacks may be relatively common among postmenopausal women and seem to be associated with stressful life events, medical comorbidity, and functional impairment.
Publication
172
Association of glycemic load with cardiovascular disease risk factors: The Women's Health Initiative Observational StudyJames Shikany
Shikany JM, Tinker LF, Neuhouser ML, Ma Y, Patterson RE, Phillips LS, Liu S, Redden DT. Association of glycemic load with cardiovascular disease risk factors: The Women's Health Initiative Observational Study. Nutrition. 2010 Jun;26(6):641-7. Epub 2010 Jan 6
glycemic load, FFQ, cholesterolBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/20053533https://www.whi.org/researchers/bibliography/Manuscripts/ms172.pdf
AS111
Associations between dietary glycemic load (GL) and cardiovascular disease risk factors, including plasma lipoprotein/lipid levels, blood pressure, and glucose metabolism factors, in the Women's Health Initiative Observational Study were examined.A random sample of 878 Observational Study participants (postmenopausal women 50-79 y of age) with baseline blood measurements (647 white, 104 black, 127 Hispanic) was included. Dietary GL was estimated from baseline food-frequency questionnaires, which assessed dietary intake over the previous 3 mo. At the baseline visit, participants completed demographic and health habit questionnaires, fasting blood samples were collected, anthropometric measurements were completed, and blood pressure was assessed.In all participants combined, GL was inversely associated with high-density lipoprotein cholesterol (P for trend = 0.004) and positively associated with log(10)-transformed triacylglycerols (P = 0.008). Although there were no statistically significant interactions of race/ethnicity with associations between GL and cardiovascular disease risk factors, stratified results were suggestive, showing that GL was positively associated with total cholesterol (P = 0.018) and low-density lipoprotein cholesterol (P = 0.038) in Hispanics. In white subjects, there was a trend of reduced high-density lipoprotein cholesterol with higher GL (P = 0.003), whereas GL was positively associated with log(10)-transformed triacylglycerols (P = 0.015). Associations between GL and high-density lipoprotein cholesterol and between GL and triacylglycerols also differed by body mass index, although the interactions were not statistically significant.Among these generally healthy postmenopausal women, GL was associated with high-density lipoprotein cholesterol and triacylglycerols. Suggestive effects of race/ethnicity and body mass index on these associations need to be confirmed in larger studies.
Publication
173
The effect of hypertension and baseline blood pressure on cognitive decline and dementia in postmenopausal women: The Women's Health Initiative Memory StudyKaren Johnson
Johnson KC, Margolis KL, Espeland MA, Colenda CC, Fillit H, Manson JE, Masaki KH, Mouton CP, Prineas R, Robinson JG, Wassertheil-Smoller S; for the Women's Health Initiative Memory Study and Women's Health Initiative Investigators. A prospective study of the effect of hypertension and baseline blood pressure on cognitive decline and dementia in postmenopausal women: The Women's Health Initiative Memory Study. J Am Geriatr Soc. 2008 Aug;56(8):1449-58. Epub 2008 Jul 15
cognition, blood pressure, antihypertensive medicationsMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18637980https://www.whi.org/researchers/bibliography/Manuscripts/ms173.pdf
AS39
To examine the relationship between baseline hypertension, blood pressure, and the development of cognitive decline in participants in the Women's Health Initiative Memory Study (WHIMS).Prospective analyses.Thirty-nine centers.Seven thousand one hundred forty-nine women aged 65 and older.The Modified Mini-Mental State Examination (3MS) was used to assess global cognitive functioning. Participants who scored below pre-established cutpoints were scheduled for more-extensive neurocognitive assessments. Results from these assessments were centrally adjudicated.The mean age of this group of 7,149 participants at baseline was 71.0 +/- 3.8, and the mean 3MS score was 95.2 +/- 4.3. During a mean follow-up period of 4.5 years, women without hypertension tended to have slightly higher 3MS scores than women with hypertension (P=.001), but the difference was not seen after adjustment for covariates (P=.17). Women with hypertension also appeared to be at greater risk for probable dementia or mild cognitive impairment (MCI) (hazard ratio=1.35, 95% confidence interval=1.07-1.70, P=.01), although when potential cofounders were accounted for, this association was no longer significant (P=.06).Hypertension and high blood pressure at baseline were not independently associated with MCI or probable dementia over time in older, cognitively intact, postmenopausal women enrolled in WHIMS after other potential confounders were taken into account. These analyses should not be viewed as discouraging appropriate medical treatment for hypertension.
Publication
174
Statin use and breast cancer: Prospective results from the Women’s Health InitiativeJane Cauley
Cauley JA, McTiernan A, Rodabough RJ, LaCroix A, Bauer DC, Margolis KL, Paskett ED, Vitolins MZ, Furberg CD, Chlebowski RT, Women's Health Initiative Research Group. Statin use and breast cancer: Prospective results from the Women's Health Initiative. J Natl Cancer Inst. 2006 May 17;98(10):700-7.
statin, breast cancerObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16705124https://www.whi.org/researchers/bibliography/Manuscripts/ms174.pdf
Despite experimental observations suggesting that 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have antitumor activity, clinical studies have reached mixed conclusions about the relationship between statin use and breast cancer risk.To investigate associations between potency, duration of use, and type of statin used and risk of invasive breast cancer, we examined data for 156,351 postmenopausal women who were enrolled in the Women's Health Initiative. Information was collected on breast cancer risk factors and on the use of statins and other lipid-lowering drugs. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical tests were two-sided.Over an average follow-up of 6.7 years, 4383 invasive breast cancers were confirmed by medical record and pathology report review. Statins were used by 11,710 (7.5%) of the cohort. Breast cancer incidence was 4.09 per 1000 person-years (PY) among statin users and 4.28 per 1000 PY among nonusers. In multivariable models, the hazard ratio of breast cancer among users of any statin, compared with nonusers, was 0.91 (95% CI = 0.80 to 1.05, P = .20). There was no trend in risk by duration of statin use, with HR = 0.80 (95% CI = 0.63 to 1.03) for < 1 year of use, HR = 0.99 (95% CI = 0.80 to 1.23) for 1- < 3 years of use, and HR = 0.94 (95% CI = 0.75 to 1.18) for > or = 3 years of use. Hydrophobic statins (i.e., simvastatin, lovastatin, and fluvastatin) were used by 8106 women, and their use was associated with an 18% lower breast cancer incidence (HR = 0.82, 95% CI = 0.70 to 0.97, P = .02). Use of other statins (i.e., pravastatin and atorvastatin) or nonstatin lipid-lowering agents was not associated with breast cancer incidence.Overall statin use was not associated with invasive breast cancer incidence. Our finding that use of hydrophobic statins may be associated with lower breast cancer incidence suggests possible within-class differences that warrant further evaluation.
Publication
176
Predicting risk of breast cancer in postmenopausal women by hormone receptor statusRowan Chlebowski
Chlebowski RT, Anderson GL, Lane DS, Aragaki AK, Rohan T, Yasmeen S, Sarto G, Rosenberg CA, Hubbell FA, For The Women's Health Initiative Investigators. Predicting risk of breast cancer in postmenopausal women by hormone receptor status. J Natl Cancer Inst. 2007 Nov 21;99(22):1695-705. Epub 2007 Nov 13.
Gail model, breast cancerBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18000216https://www.whi.org/researchers/bibliography/Manuscripts/ms176.pdf
Strategies for estrogen receptor (ER)-positive breast cancer risk reduction in postmenopausal women require screening of large populations to identify those with potential benefit. We evaluated and attempted to improve the performance of the Breast Cancer Risk Assessment Tool (i.e., the Gail model) for estimating invasive breast cancer risk by receptor status in postmenopausal women.In The Women's Health Initiative cohort, breast cancer risk estimates from the Gail model and models incorporating additional or fewer risk factors and 5-year incidence of ER-positive and ER-negative invasive breast cancers were determined and compared by use of receiver operating characteristics and area under the curve (AUC) statistics. All statistical tests were two-sided.Among 147,916 eligible women, 3236 were diagnosed with invasive breast cancer. The overall AUC for the Gail model was 0.58 (95% confidence interval [CI]=0.56 to 0.60). The Gail model underestimated 5-year invasive breast cancer incidence by approximately 20% (P<.001), mostly among those with a low estimated risk. Discriminatory performance was better for the risk of ER-positive cancer (AUC = 0.60, 95% CI = 0.58 to 0.62) than for the risk of ER-negative cancer (AUC = 0.50, 95% CI = 0.45 to 0.54). Age and age at menopause were statistically significantly associated with ER-positive but not ER-negative cancers (P=.05 and P=.04 for heterogeneity, respectively). For ER-positive cancers, no additional risk factors substantially improved the Gail model prediction. However, a simpler model that included only age, breast cancer in first-degree relatives, and previous breast biopsy examination performed similarly for ER-positive breast cancer prediction (AUC=0.58, 95% CI= 0.56 to 0.60); postmenopausal women who were 55 years or older with either a previous breast biopsy examination or a family history of breast cancer had a 5-year breast cancer risk of 1.8% or higher.In postmenopausal women, the Gail model identified populations at increased risk for ER-positive but not ER-negative breast cancers. A model with fewer variables appears to provide a simpler approach for screening for breast cancer risk.
Publication
177
Validity of self-report for fractures among a multiethnic cohort of postmenopausal women: Results from the Women's Health Initiative observational study and clinical trialsZhao Chen
Chen Z, Kooperberg C, Pettinger MB, Bassford T, Cauley JA, LaCroix AZ, Lewis CE, Kipersztok S, Borne C, Jackson RD. Validity of self-report for fractures among a multiethnic cohort of postmenopausal women: Results from the Women's Health Initiative observational study and clinical trials. Menopause. 2004 May-Jun;11(3):264-74.
WHI, self report for fracture, validity, clinical trial, observational study, postmenopausal womenBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15167305https://www.whi.org/researchers/bibliography/Manuscripts/ms177.pdf
The purpose of this study is to examine the validity of, and factors associated with, the accuracy of self-report (participant-report and proxy-report) for fractures.Study participants were from the Women's Health Initiative Clinical Trial and Observational Study cohorts. All women were postmenopausal; populations included American Indian, Asian/Pacific Islander, black, Hispanic, and non-Hispanic white. The average length of follow-up was 4.3 years. Self-reported fractures were adjudicated by reviewing medical records. The first adjudicated self-report of fractures for each participant was included in the analysis (n = 6,652).We found substantial variations in validity of self-report by the fracture site. Agreements between self-reports for single-site fractures and medical records were high for hip (78%) and forearm/wrist (81%) but relatively lower for clinical spine fractures (51%). The average confirmation rate for all single-site fractures was 71%. Misidentification of fracture sites by participants or proxy-reporters seemed to be a cause of unconfirmed self-reports. Higher confirmation rates were observed in participant-reports than in proxy-reports. Results of the multivariate analysis indicated that multiple factors, such as ethnicity, a history of osteoporosis or fractures, body mass index, years since menopause, smoking status, and number of falls in the past year were significantly (P < 0.05) related to the validity of self-report.The validity of self-reports for fracture varies by fracture sites and many other factors. The assessed validity in this study is likely conservative because some of the unconfirmed self-reports may be due to poor medical record systems. The validity of self-reports for hip and forearm/wrist fractures is high in this study, supporting their use in epidemiological studies among postmenopausal women.
Publication
179
Progression and remission of pelvic organ prolapse: A longitudinal study of menopausal womenVictoria Handa
Handa VL, Garrett E, Hendrix S, Gold E, Robbins J. Progression and remission of pelvic organ prolapse: A longitudinal study of menopausal women. Am J Obstet Gynecol. 2004 Jan;190(1):27-32.
pelvic organ prolapse, cystocele, rectocele, natural historyClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/14749630https://www.whi.org/researchers/bibliography/Manuscripts/ms179.pdf
The purpose of this study was to describe the natural history of pelvic organ prolapse after menopause.Over 2 to 8 years, participants in the estrogen plus progestin trial of the Women's Health Initiative at the University of California Davis had annual pelvic examinations, with an assessment of uterine prolapse, cystocele, and rectocele. The findings from these examinations were used to describe the incidence of pelvic organ prolapse, the probability of progression or regression, and the associated risk factors.At baseline, 31.8% of women had pelvic organ prolapse (n=412 women). The annual incidences of cystocele, rectocele, and uterine prolapse were 9.3, 5.7, and 1.5 cases per 100 women-years, respectively. Incident prolapse was associated with increasing parity and waist circumference. The progression rates for grade 1 pelvic organ prolapse (per 100 women-years) were 9.5 for cystocele, 13.5 for rectocele, and 1.9 for uterine prolapse. The annual rates of regression (per 100 women-years) was 23.5, 22, and 48, respectively.Our data suggest that pelvic organ prolapse is not always chronic and progressive as traditionally thought. Spontaneous regression is common, especially for grade 1 prolapse.
Publication
181
Alcohol and folate intake and breast cancer risk in the WHI Observational StudyChristine Duffy
Duffy CM, Assaf A, Cyr M, Burkholder G, Coccio E, Rohan T, McTiernan A, Paskett E, Lane D, Chetty VK. Alcohol and folate intake and breast cancer risk in the WHI Observational Study. Breast Cancer Res Treat. 2009 Aug;116(3):551-62. Epub 2008 Sep 11.
alcohol, breast cancer, cancer, postmenopausal women, folic acid intake, risk factorsObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18785003https://www.whi.org/researchers/bibliography/Manuscripts/ms181.pdf
Alcohol increases breast cancer risk. Epidemiological studies suggest folate may modify this relationship.To examine the relationship among breast cancer, alcohol and folate in the Women's Health Initiative-Observational Study (WHI-OS).88,530 postmenopausal women 50-79 years completed baseline questionnaires between October 1993 and December 1998, which addressed alcohol and folate intake and breast cancer risk factors. Cox proportional hazards analysis examined the relationship between self-reported baseline alcohol and folate intake and incident breast cancer.1,783 breast cancer cases occurred over 5 years. Alcohol was associated with increased risk of breast cancer (RR = 1.005, 95%CI 1.001-1.009). Risk increased with consumption of alcohol (up to 5 g/d, adjusted HR = 1.10, 95%CI 0.96-1.32; >5-15 g/d HR = 1.14, 95%CI 0.99-1.31; and >15 g/d HR = 1.13 95%CI 0.96-1.32). We found no significant interaction between alcohol and folate in our adjusted model.We found no evidence for folate attenuating alcohol's effect on breast cancer risk in postmenopausal women. Our results may be due to misclassification of folate intake or the relatively short follow-up period.
Publication
183
Panic attacks, daily life ischemia, and chest pain in postmenopausal womenJordan Smoller
Smoller JW, Pollack MH, Wassertheil-Smoller S, Brunner R, Curb D, Torner J, Oberman A, Hendrix SL, Hsia J, Sheps DS. Panic attacks, daily life ischemia, and chest pain in postmenopausal women. Psychosom Med. 2006 Nov-Dec;68(6):824-32. Epub 2006 Nov 13.
panic attacks, myocardial ischemia, Holter monitoring, chest painBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/17101813https://www.whi.org/researchers/bibliography/Manuscripts/ms183.pdf
AS70
Chest pain is a common symptom of panic attacks, but little is known about the relationship in older women among panic attacks, chest pain, and daily life ischemia.The authors conducted a cross-sectional survey of 3063 community-dwelling, generally healthy postmenopausal women enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study in 10 clinical centers of the 40-center Women's Health Initiative. Participants, ages 50 to 79 years, completed a questionnaire about occurrence of panic attacks in the previous 6 months and underwent 24-hour ambulatory electrocardiogram monitoring (AECG); 2705 women had valid AECG recordings and panic attack questionnaires. ST depression on AECG, heart rate variability (HRV), and chest pain episodes were compared among women with and without a 6-month history of panic attack.There was no difference in overall prevalence of ischemic episodes during AECG between women with and without panic attacks. Women with a recent history of panic were more likely to experience chest pain during AECG after controlling for potential confounders (odds ratio [OR] = 2.01; 95% confidence interval [CI] = 1.40-2.88), including both nonischemic (OR = 1.83; 95% CI = 1.26-2.65) and ischemic chest pain (OR = 4.94; 95% CI = 1.41-17.30). Although mean HRV was lower in those with panic attacks (p = .017), this was not significant after controlling for confounders.Postmenopausal women with a recent history of panic attacks do not appear to have more daily life ischemia as measured by occurrence of ST depression during 24-hour monitoring, but do have more chest pain and possibly lower HRV, suggesting that even sporadic panic attacks may be related to cardiovascular risk.
Publication
186
Physical activity and diabetes risk in postmenopausal womenJudith Hsia
Hsia J, Wu L, Allen C, Oberman A, Lawson WE, Torrens J, Safford M, Limacher MC, Howard BV, Women's Health Initiative Research Group. Physical activity and diabetes risk in postmenopausal women. Am J Prev Med. 2005 Jan;28(1):19-25.
Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15626551https://www.whi.org/researchers/bibliography/Manuscripts/ms186.pdf
To evaluate the hypothesis that physical activity independently predicts type 2 diabetes risk in postmenopausal African-American, Hispanic, Asian, and Caucasian women.We prospectively evaluated the relationship between incident type 2 diabetes, walking, and total physical activity at baseline in the Women's Health Initiative Observational Study. Baseline data were collected between September 1994 and December 1998; incident diabetes was identified through August 2002. Hazard ratios for self-reported diabetes adjusted for body mass index (BMI) and other variables were evaluated across categories of physical activity in Caucasian, African-American, Hispanic, and Asian/Pacific Islander women.Incident diabetes was reported by 2.2% of Caucasian, 6.2% of African-American, 4.5% of Hispanic, 3% of Asian, and 5.7% of American Indian women (p <0.0001 across ethnic groups) during 458,018 woman-years of follow-up. Among Caucasian women, walking (multivariate-adjusted hazard ratios 1.00, 0.85, 0.87, 0.75, 0.74; p <0.001 for trend across exercise quintiles) and total physical activity score (hazard ratios 1.00, 0.88, 0.74, 0.80, 0.67; p =0.002) demonstrated a strong inverse relationship with diabetes risk. In BMI-adjusted models, African-American women in higher physical activity categories were less likely to develop diabetes than women in the lowest physical activity category. After adjusting for age and multiple risk factors, however, no significant association between physical activity and diabetes risk was apparent for African-American, Hispanic, or Asian women.These findings suggest a stronger and more independent association of physical inactivity with development of diabetes in Caucasian women than in minority women, but could also be explained by less precise risk estimates in minority women or the role of chance.
Publication
187
Postmenopausal hormone therapy and cardiovascular diseaseJacques Rossouw
Rossouw, J. E. (2002) Postmenopausal Hormone Therapy and Cardiovascular Disease, in Evidence-based Cardiology, Second Edition (eds S. Yusuf, J. A. Cairns, A. J. Camm, E. L. Fallen and B. J. Gersh), BMJ Books, London, UK. Doi: 10.1002/9780470986882.ch20
women, cardiovascular disease, stroke,  pulmonary embolism, CHD, sex differentialObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/Ms187.pdf
Publication
188
Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: The Women's Health InitiativePentti Rautaharju
Rautaharju PM, Kooperberg C, Larson JC, LaCroix A. Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: The Women's Health Initiative. Circulation. 2006 Jan 31;113(4):473-80.
cardiovascular diseases, electrocardiography, morbidity, mortality, womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16449726https://www.whi.org/researchers/bibliography/Manuscripts/ms188.pdf
Information is limited about the independent prognostic value of repolarization abnormalities in women.We evaluated hazard ratios for ECG variables for combined fatal and nonfatal coronary heart disease (CHD) events and for CHD mortality using Cox regression in 38,283 Women's Health Initiative (WHI) participants during up to 9.2 years of follow-up. All risk models were adjusted for demographic, clinical, and therapeutic variables. Evaluated as single ECG variables, wide QRS/T angle and ECG-demonstrated myocardial infarction (ECG-MI) were the strongest predictors of CHD events, with hazard ratios (95% CI) of 1.90 (1.50 to 2.42) and 1.62 (1.29 to 2.03), respectively. Six other repolarization variables were also significant, strong predictors of CHD events. Wide QRS/T angle, ECG-MI, and QT prolongation appeared as dominant predictors when evaluated simultaneously with other ECG variables in a multiadjusted risk model. QRS/T angle, ECG-MI, and high QRS nondipolar voltage were the strongest predictors of CHD mortality, with hazard ratios of 2.70, 2.41, and 2.18, respectively. The risk increase ranged from 63% to 95% for the other 4 significant predictors. Five ECG abnormalities were identified as dominant mortality risk predictors: wide QRS/T angle, ECG-MI, high QRS nondipolar voltage, reduced heart rate variability, and QT prolongation (in the cardiovascular disease-free group only).Ventricular repolarization abnormalities in postmenopausal women are as important predictors of CHD events and CHD mortality as ECG-MI and other QRS abnormalities. Repolarization variables and QRS nondipolar voltage warrant attention in future investigations.
Publication
189
Dietary adherence in the Women's Health Initiative Dietary Modification TrialThe Writing Group for the WHI Investigators
Women's Health Initiative Study Group. Dietary adherence in the Women's Health Initiative Dietary Modification Trial. J Am Diet Assoc. 2004 Apr;104(4):654-8.
Dietary Fats, Female, Randomized Controlled TrialsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15054353https://www.whi.org/researchers/bibliography/Manuscripts/ms189.pdf
This article describes adherence to a low-fat dietary pattern (less than 20% energy from fat, five or more fruit/vegetable and six or more grain servings daily) in Years 1 and 5 of the Women's Health Initiative Dietary Modification Trial, which was designed to examine the effects of a low-fat dietary pattern on risk of breast and colorectal cancers and other chronic diseases in postmenopausal women. Participants were randomly assigned to a low-fat dietary intervention arm (40%, n=19,542) or a usual diet control arm (60%, n=29,294). Women in the intervention arm completed 18 group sessions during the first year, followed by quarterly annual maintenance sessions. Adherence was assessed as control minus intervention (C-I) group differences in percent total energy from fat as estimated by a food frequency questionnaire. Based on these self-reported dietary data, mean C-I was 10.9 percentage points of energy from fat at Year 1, decreasing to 9.0 at Year 5. Factors associated with poorer adherence were being older, being African American or Hispanic (compared with white), having low income, and being obese. Group session attendance was strongly associated with better dietary adherence. There are many limitations of self-reported dietary data, particularly related to social desirability and intervention-associated bias. Nonetheless, these data indicate that long-term dietary change was achieved in this clinical trial setting and reinforce the potential of the ongoing trial to answer questions of public health importance.
Publication
190
Prevalence and determinants of electrocardiographic left ventricular hypertrophy among a multiethnic population of postmenopausal women (The Women's Health Initiative)Albert Oberman
Oberman A, Prineas RJ, Larson JC, LaCroix A, Lasser NL. Prevalence and determinants of electrocardiographic left ventricular hypertrophy among a multiethnic population of postmenopausal women (The Women's Health Initiative). Am J Cardiol. 2006 Feb 15;97(4):512-9. Epub 2006 Jan 4.
Left ventricular mass, CHD, women's health, CVD, risk factors, electrocardiography, metabolic syndrome, LVM, LV hypertrophyClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16461048https://www.whi.org/researchers/bibliography/Manuscripts/ms190.pdf
Our objectives were to determine the prevalence and factors related to left ventricular hypertrophy (LVH) among older women for commonly used electrocardiographic criteria. LVH is a potent risk factor for cardiovascular disease, especially among women. However, its value has been limited, in part, by the use of different electrocardiographic criteria and the lack of a clearly defined standard for the general population. A total of 3,613 eligible women, aged 50 to 79 years, underwent medical history, physical measurements, and biochemical determinations and had behavioral factors recorded at baseline. Three LVH indexes were derived from computer measurement of the electrocardiogram: hypertrophied left ventricular mass > or =171.04 g (HLVM); Cornell voltage > or =2,200 microV; and Minnesota Code items. The prevalence of LVH ranged from <1% to 13% when stratified by age, ethnicity, and scoring technique. Baseline traits differed significantly for those meeting the LVH criteria. Predictors (p <0.01) of HLVM were age (odds ratio 0.66), height (odds ratio 1.47), waist/hip ratio (odds ratio 1.30), systolic blood pressure (odds ratio 1.18); low-density lipoprotein cholesterol (odds ratio 0.97), log insulin (odds ratio 2.10), dietary kilocalories (odds ratio 1.16), weekly energy expenditure (odds ratio 0.53), hypertension (odds ratio 1.61), current estrogen use (odds ratio 0.60), and current smoker (odds ratio 0.47). The presence of the metabolic syndrome was related to all LVH indexes, with odds ratios of 4.95, 2.24, and 2.35, respectively, for HLVM, Cornell voltage, and Minnesota Code. In conclusion, the prevalence of LVH varied by ethnicity and the electrocardiographic index used. However, the baseline traits, especially the factors associated with the metabolic syndrome, were consistently and strongly related to all LVH indexes, particularly HLVM. Intervention on these factors may provide strategies for reducing LVH, a strong independent risk factor for cardiovascular morbidity and mortality among women.
Publication
192
Bone mineral density of American Indian and Alaska Native women compared with non-Hispanic white women: Results from the Women's Health Initiative StudyNina Wampler
Wampler NS, Chen Z, Jacobsen C, Henderson JA, Howard BV, Rossouw JE. Bone mineral density of American Indian and Alaska Native women compared with non-Hispanic white women: results from the Women's Health Initiative Study. Menopause. 2005 Sep-Oct;12(5):536-44. Epub 2005 Sep 1.
bone mineral density, osteoporosis risk factors, American Indian and Alaska Native, reproductive factors, body mass index, calcium intakeBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16145307https://www.whi.org/researchers/bibliography/Manuscripts/ms192.pdf
To compare bone mineral density (BMD) of American Indian/Alaska Native (AI/AN) women with that of non-Hispanic white women.This cross-sectional study compared mean BMD between AI/AN women and a random sample of non-Hispanic white women matched on geographic region in the Women's Health Initiative Study, a prospective study of postmenopausal women. We analyzed baseline BMD measurements for the total hip, spine, and whole body from 139 AI/AN women and 1,431 non-Hispanic white women.Unadjusted mean spine and whole body BMDs were not significantly different between the two races. Controlling for age, education, and hormone therapy use, adjusted mean BMD was similar by race among women who were underweight, normal, or obese. We found a significant interaction of race by body mass index on spine (P = 0.003) and whole body (P = 0.0003) BMD; thus, analyses were stratified by body mass index. Overweight AI/AN women had slightly lower adjusted mean whole body and spine BMD than overweight non-Hispanic white women (whole body: 0.97 vs 1.03 g/cm, P = 0.02; spine: 0.96 versus 1.03 g/cm, P = 0.001). Among extremely obese (body mass index: > or =40.0 kg/m) women, adjusted mean total hip BMD was higher in the AI/AN women (1.07 vs 0.97 g/cm, respectively, P = 0.03).Overall, AI/AN and non-Hispanic white women had similar BMDs. This study suggests that extremely obese AI/AN women may have higher BMD at certain skeletal sites compared with extremely obese non-Hispanic white women. However, these results need to be confirmed by additional research.
Approved Proposal
194
Predictors of adherence to the hormone replacement therapy clinical trial in the Women’s Health InitiativeBarb Cochrane
hormone replacement, adherence, postmenopausal women, clinical trialClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/ms194p.pdf
Publication
195
Predictors of adherence in the Women's Health Initiative Calcium and  TrialRobert Brunner
Brunner R, Dunbar-Jacob J, Leboff MS, Granek I, Bowen D, Snetselaar LG, Shumaker SA, Ockene J, Rosal M, Wactawski-Wende J, Cauley J, Cochrane B, Tinker L, Jackson R, Wang CY, Wu L. Predictors of adherence in the Women's Health Initiative Calcium and Vitamin D Trial. Behav Med. 2009 Winter;34(4):145-55.
Calcium/Vitamin D, Supplementation, Clinical Trial, Prevention, Adherence, Predictors, womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19064373https://www.whi.org/researchers/bibliography/Manuscripts/ms195.pdf
The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking > or = 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial.
Publication
196
Predictors of dietary change and maintenance in the Women's Health Initiative Dietary Modification TrialLesley Tinker
Tinker LF, Rosal MC, Young AF, Perri MG, Patterson RE, Van Horn L, Assaf AR, Bowen DJ, Ockene J, Hays J, Wu L. Predictors of dietary change and maintenance in the Women's Health Initiative Dietary Modification Trial. J Am Diet Assoc. 2007 Jul;107(7):1155-65.
dietary adherence, low-fat eating pattern, postmenopausal women, behavioral and psychosocial predictorsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17604744https://www.whi.org/researchers/bibliography/Manuscripts/ms196.pdf
To identify predictors of dietary change to and maintenance of a low-fat eating pattern (<20% energy from fat, > or = 5 servings fruits/vegetables daily, and > or = 6 servings grains daily) among a cohort of postmenopausal women. Candidate predictors included intrapersonal, interpersonal, intervention program characteristics, and clinical center.Longitudinal study within the Women's Health Initiative Dietary Modification Trial. Dietary change was evaluated after 1 year of participation in the Women's Health Initiative Dietary Modification Trial, and dietary maintenance after 3 years.Postmenopausal women aged 50 to 79 years at baseline who were randomized to the intervention arm of the Women's Health Initiative Dietary Modification Trial (n=19,541).Univariate and multivariate linear regression analysis was performed and associations evaluated between candidate predictors and each of the three dietary goals: percent energy from fat, fruit/vegetable servings, and grain servings.Year 1 (change) predictors of percent energy from fat (P<0.005) included being younger (beta=2.12; 70 to 79 years vs 50 to 59 years), more educated (beta=-.69; college vs high school), more optimistic (beta=-.07), attending more sessions (beta=-.69), and submitting more self-monitoring records (beta=-.74). At year 3 (maintenance), the predictors of percent energy from fat (P<0.005) included attending more sessions (beta=-.65) and submitting more self-monitoring scores (beta=-.71). The analytic model predicted 22% of the variance in fat intake at year 1 and 27% at year 3 (P<0.01).The strongest predictors of dietary change and maintenance were attending intervention sessions and self-monitoring dietary intake. Novel was the finding that optimism predicted dietary change.
Publication
197
Predictors of angina pectoris versus myocardial infarction from the Women's Health Initiative Observational StudyJudith Hsia
Hsia J, Aragaki A, Bloch M, LaCroix AZ, Wallace R, WHI Investigators. Predictors of angina pectoris versus myocardial infarction from the Women's Health Initiative Observational Study. Am J Cardiol. 2004 Mar 15;93(6):673-8.
Coronary Syndrome, HRTObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15019867https://www.whi.org/researchers/bibliography/Manuscripts/ms197.pdf
Although risk factors for acute coronary syndromes have been extensively studied, characteristics distinguishing women who will develop unstable angina rather than acute myocardial infarction (MI) are less well understood. This analysis evaluates baseline demographic, physical, and medical characteristics as predictors of angina versus MI in the Women's Health Initiative Observational Study. During a prospective 4.5-year follow-up of 92,152 postmenopausal women, 1,527 hospitalizations for angina and 797 for MI were confirmed by centrally trained physician adjudicators. In a multivariate analysis of women with incident angina or MI, high cholesterol (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.47 to 0.80; p = 0.0004) and prior coronary disease (OR 0.70, 95% CI 0.55 to 0.89; p = 0.004) independently predicted angina (referent), whereas current cigarette smoking (OR 1.60, 95% CI 1.13 to 2.26; p = 0.007) and diabetes mellitus (1.44, 95% CI 1.10 to 1.87; p = 0.007) predicted MI. Older age and hypertension were independently, but less strongly, predictive of MI. Aspirin or statin use, physical activity, body mass index, and educational levels were not independently associated with one or the other type of acute coronary syndrome. Thus, specific risk factors strongly and independently predicted whether women with an acute coronary syndrome would present with angina or with MI.
Publication
198
The Women’s Health Initiative: Aspects of the management and coordinationBarb Cochrane
Cochrane BB, Lund B, Anderson S, Prentice R. The Women's Health Initiative: Aspects of management and coordination. In: Hawkins JW, Haggerty LA, eds. Diversity in health care research: strategies for multisite, multidisciplinary, and multi-ethnic projects. 1st ed. New York: Springer,2003:181-207.
WHI, postmenopausal women, women;s health, clinical trials, oberstvational studies, coordinating centers, managementBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms198.pdf
Publication
200
Expression and ambivalence over expression of negative emotion: Psychometric analysis in the Women's Health InitiativeYvonne Michael
Michael YL, Perrin N, Bowen D, Cochrane BB, Wisdom JP, Brzyski R, Ritenbaugh C. Expression and ambivalence over expression of negative emotion: Psychometric analysis in the Women's Health Initiative. J Women Aging. 2005;17(1-2):5-18.
Emotion, Psychosocial, Behavioral, Health-related quality of life, Psychometric, Validation, Race/ethnicityBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15914416https://www.whi.org/researchers/bibliography/Manuscripts/ms200.pdf
Inhibition of emotional expression has been associated with the incidence and progression of breast cancer and other chronic illnesses. Others have theorized that it may not be repression itself, but rather ambivalence over the expression of emotions that is the important health-related factor. The Women's Health Initiative (WHI), a long-term, national study focusing on disease prevention among postmenopausal women, is unique in its assessment of expression and ambivalence of negative emotion in a large study sample of multiethnic, older women. Psychological factors such as expression of negative emotion and ambivalence about expression of emotion are also determined by social patterning. The current study examined the psychometric properties of the instruments used to measure each construct and variation across race/ethnicity and age. The analysis suggests that the scales can be used with confidence in diverse ethnic and age groups. Examining ambivalence about expression of negative emotion in future longitudinal research will further elucidate its role in predicting disease incidence and recovery, both important in reducing the public health burden of chronic disease.
Publication
201
Normal standards for QT and QT subintervals derived from a large ethnically diverse population of women aged 50 to 79 years (the Women's Health Initiative [WHI])Pentti Rautaharju
Rautaharju PM, Prineas RJ, Kadish A, Larson JC, Hsia J, Lund B. Normal standards for QT and QT subintervals derived from a large ethnically diverse population of women aged 50 to 79 years (The Women's Health Initiative [WHI]). Am J Cardiol. 2006 Mar 1;97(5):730-7. Epub 2006 Jan 11.
normal standards, QT, QRS and PR intervals, ECG wave amplitudes, ECG phenotypes, repolarization, women, age, race, obesity, blood pressureBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16490447https://www.whi.org/researchers/bibliography/Manuscripts/ms201.pdf
Available normal standards for rate-adjusted QT intervals in women are based on samples that include only whites, and no normal standards are available for QT subintervals. This study derived normal limits from percentile distributions for QT as well as QT and T-wave subintervals in 22,311 participants in the Women's Health Initiative (WHI), including 19,059 white, 1,771 African-American, 819 Hispanic, 82 American Indian, and 580 Asian women. Excluded were women with cardiovascular disease or who were using cardioactive drugs at baseline and cardiovascular morbidity or death during the subsequent mean 6.3-year follow-up. Normal limits for QT adjusted by Bazett's formula were strongly rate dependent, invalidating their use in practical applications. QT adjusted as a linear function of RR (QTrr) or by power functions of RR with exponent 0.5 (QTsqr) or 0.42 (QT0.42) using an appropriate regression function produced rate-invariant upper and lower normal limits for rate-adjusted QT. Adjusted QT is preferable to adjusted JT because the latter requires the incorporation of QRS duration as a covariate with RR. Normal limits were also derived for T-wave subintervals. Normal limits of QTrr in Asian women were 10 ms longer than in other ethnic groups. In conclusion, QT adjusted for rate as a linear function of RR is preferable to JT and other QT subintervals in the evaluation of QT prolongation. The adaptation of considerable revisions of the currently used limits for prolonged QT in women is suggested, with an additional race-specific adjustment in Asian women. Bazett's formula is inappropriate for testing new drugs or other applications.
Publication
202
Depressive symptoms and heart rate variability in postmenopausal womenDavid Sheps
Kim CK, McGorray SP, Bartholomew BA, Marsh M, Dicken T, Wassertheil-Smoller S, Curb JD, Oberman A, Hsia J, Gardin J, Wong ND, Barton B, McMahon RP, Sheps DS. Depressive symptoms and heart rate variability in postmenopausal women. Arch Intern Med. 2005 Jun 13;165(11):1239-44.
Menopause, women, heart rate variability, depression, coronary artery disease.Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15956002https://www.whi.org/researchers/bibliography/Manuscripts/ms202.pdf
Depressive symptoms have been associated with increased cardiac morbidity and mortality rates, but the pathophysiologic mechanism linking depressive symptoms to cardiovascular outcome has yet to be fully understood. Lower heart rate variability has also been associated with increased risk of cardiac events in healthy individuals and in patients with coronary artery disease. Findings regarding a relationship between depressive symptoms and heart rate variability that could explain increased cardiovascular risk have been inconsistent across studies.As an ancillary study to the Women's Health Initiative Observational Study, 3372 postmenopausal women aged 50 to 83 years were enrolled for further evaluation using 24-hour ambulatory electrocardiographic monitoring. A shortened version of the Center for Epidemiological Studies Depression Scale and the Diagnostic Interview Schedule were administered. Women with adequate electrocardiographic data and depressive symptom information and without coronary artery disease were analyzed (n = 2627).Two hundred sixty-nine women (10.2%) had depressive symptoms as measured using the 2 instruments. Women with depressive symptoms had a higher mean +/- SD heart rate (77.4 +/- 9.6 vs 75.5 +/- 8.5 beats/min) and lower heart rate variability than women without depressive symptoms. All differences remained significant after adjusting for age (P<.01).Women with depressive symptoms had significant reductions in heart rate variability and higher heart rates, suggestive of increased sympathetic tone. These findings may contribute to the increased cardiac morbidity and mortality rates associated with depression in other studies.
Publication
203
Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women's Health Initiative Randomized TrialRowan Chlebowski
Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A, WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: The Women's Health Initiative Randomized Trial. JAMA. 2003 Jun 25;289(24):3243-53.
breast cancer, estrogen, progestin, HRT, clinical trialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12824205https://www.whi.org/researchers/bibliography/Manuscripts/ms203.pdf
The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
Publication
204
Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: A randomized trialSylvia Wassertheil-Smoller
Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, Kotchen T, Curb JD, Black H, Rossouw JE, Aragaki A, Safford M, Stein E, Laowattana S, Mysiw WJ, WHI Investigators. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: A randomized trial. JAMA. 2003 May 28;289(20):2673-84.
Stroke, estrogen, progestin, HRT, clinical trialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12771114https://www.whi.org/researchers/bibliography/Manuscripts/ms204.pdf
W1, W6
The Women's Health Initiative (WHI) trial of estrogen plus progestin was stopped early because of adverse effects, including an increased risk of stroke in the estrogen plus progestin group.To assess the effect of estrogen plus progestin on ischemic and hemorrhagic stroke and in subgroups, and to determine whether the effect of estrogen plus progestin was modified by baseline levels of blood biomarkers.Multicenter double-blind, placebo-controlled, randomized clinical trial involving 16 608 women aged 50 through 79 years with an average follow-up of 5.6 years. Baseline levels of blood-based markers of inflammation, thrombosis, and lipid levels were measured in the first 140 centrally confirmed stroke cases and 513 controls.Participants received 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).Overall strokes and stroke subtype and severity were centrally adjudicated by stroke neurologists.One hundred fifty-one patients (1.8%) in the estrogen plus progestin and 107 (1.3%) in the placebo groups had strokes. Overall 79.8% of strokes were ischemic. For combined ischemic and hemorrhagic strokes, the intention-to-treat hazard ratio (HR) for estrogen plus progestin vs placebo was 1.31 (95% confidence interval [CI], 1.02-1.68); with adjustment for adherence, the HR was 1.50 (95% CI, 1.08-2.08). The HR for ischemic stroke was 1.44 (95% CI, 1.09-1.90) and for hemorrhagic stroke, 0.82 (95% CI, 0.43-1.56). Point estimates of the HRs indicate that excess risk of all stroke was apparent in all age groups, in all categories of baseline stroke risk, and in women with and without hypertension, prior history of cardiovascular disease, use of hormones, statins, or aspirin. Other risk factors for stroke, including smoking, blood pressure, diabetes, lower use of vitamin C supplements, blood-based biomarkers of inflammation, higher white blood cell count, and higher hematocrit levels did not modify the effect of estrogen plus progestin on stroke risk.Estrogen plus progestin increases the risk of ischemic stroke in generally healthy postmenopausal women. Excess risk for all strokes attributed to estrogen plus progestin appeared to be present in all subgroups of women examined.
Approved Proposal
205
Risk factors for sarcopenia among a multiethnic cohort of postmenopausal womenZhao Chen
none providedBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms205p.pdf
Publication
206
Fracture risk among breast cancer survivors: Results from the Women's Health Initiative Observational StudyZhao Chen
Chen Z, Maricic M, Bassford TL, Pettinger M, Ritenbaugh C, Lopez AM, Barad DH, Gass M, Leboff MS. Fracture risk among breast cancer survivors: results from the Women's Health Initiative Observational Study. Arch Intern Med. 2005 Mar 14;165(5):552-8.
breast Cancer, OsteoporosisBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15767532https://www.whi.org/researchers/bibliography/Manuscripts/ms206.pdf
Breast cancer and its treatment may compromise bone health. We tested the hypothesis in the Women's Health Initiative Observational Study that postmenopausal survivors of breast cancer have a higher risk for fractures compared with women who have no cancer history.A prospective cohort (5.1 years' follow-up) study design was used. Breast cancer survivors were women who reported a history of breast cancer (n = 5298). A reference group included women who had no cancer history at baseline (n = 80 848). Fracture occurrence was ascertained from annual self-reports. Hip fractures were confirmed by reviewing medical records.After adjustment for age, weight, ethnicity, and geographic region of enrollment, the hazard ratios (HRs) of breast cancer survivors to women in the reference group were 0.93 (95% confidence interval [CI], 0.64-1.33) for hip; 1.36 (95% CI, 1.16-1.59) for forearm or wrist; 1.31 (95% CI, 1.19-1.43) for eligible fractures other than hip, vertebral, and forearm or wrist; and 1.31 (95% CI, 1.21-1.41) for these fractures combined. The increased risk for clinical vertebral fracture was statistically significant only among survivors who had a breast cancer diagnosis before age 55 years (HR, 1.78; 95% CI, 1.28-2.46). After adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle, the increased risk for all fractures studied among survivors was reduced to 15% (HR, 1.15; 95% CI, 1.05-1.25).Postmenopausal survivors of breast cancer are at increased risk for clinical fractures. Preventions and therapeutic interventions are needed to reduce fracture risk in this large and growing population.
Publication
208
Effects of estrogen plus progestin on risk of fracture and bone mineral density: The Women's Health Initiative randomized trialJane Cauley
Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, Pettinger M, Stefanick ML, Wactawski-Wende J, Watts NB, Women's Health Initiative Investigators. Effects of estrogen plus progestin on risk of fracture and bone mineral density: The Women's Health Initiative randomized trial. JAMA. 2003 Oct 1;290(13):1729-38.
Estrogen, Progestin, Fractures, Clinical TrialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/14519707https://www.whi.org/researchers/bibliography/Manuscripts/ms208.pdf
In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures.To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures.Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years.Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk.Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P<.001). The HR for the global index was similar across tertiles of the fracture risk scale (lowest fracture risk tertile, HR, 1.20; 95% CI, 0.93-1.58; middle tertile, HR, 1.23; 95% CI, 1.04-1.46; highest tertile, HR, 1.03; 95% CI, 0.88-1.24) (P for interaction =.54).This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.
Publication
209
Obesity, hormone therapy, estrogen metabolism and risk of postmenopausal breast cancerFrancesmary Modugno
Modugno F, Kip KE, Cochrane B, Kuller L, Klug TL, Rohan TE, Chlebowski RT, Lasser N, Stefanick ML. Obesity, hormone therapy, estrogen metabolism and risk of postmenopausal breast cancer. Int J Cancer. 2006 Mar 1;118(5):1292-301
breast Cancer, Hormone Replacement Therapy, Estrogen Metabolites, Body Mass IndexObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16161054https://www.whi.org/researchers/bibliography/Manuscripts/ms209.pdf
AS134
Hormone therapy (HT) and body mass index (BMI) have been associated with postmenopausal breast cancer. Because estrogen metabolism may affect breast cancer risk and can be altered by weight and HT, it might play a role in the HT-BMI-breast cancer associations. We undertook a nested case-control study within the Observational Study of the Women's Health Initiative. Baseline levels of 2- and 16alpha-hydroxy estrone (2-OHE1 and 16alpha-OHE1) were measured in 200 women who developed breast cancer during follow-up and 200 healthy controls matched to cases by ethnicity, enrollment date, clinic site, type of HT and years since menopause. Wilcoxon nonparametric tests were used to compare estrogen metabolite levels between cases and controls. Conditional logistic regression was used to assess the relationship between BMI, estrogen metabolites and breast cancer risk. 16alpha-OHE1 levels were modestly but significantly higher in HT users among cases (median 356 pg/ml vs. 315 pg/ml) and controls (354 pg/ml vs. 298 pg/ml). 2-OHE1 levels were substantially and significantly higher in HT users among cases (369 pg/ml vs. 125 pg/ml) and controls (347 pg/ml vs. 134 pg/ml). For non-HT users only, greater BMI and higher 16alpha-OHE1 levels were individually and jointly associated with increased breast cancer risk (OR for women with high BMI and high 16alpha-OHE1 compared to those with low BMI and low 16alpha-OHE1 = 3.51, 95% CI = 1.34-9.16). No associations between BMI, estrogen metabolism and breast cancer risk were found for HT users. Estrogen metabolism differs according to both BMI and HT use, potentially explaining the interaction between BMI and HT in relation to breast cancer risk.
Publication
210
Estrogen plus progestin and the risk of coronary heart diseaseJoAnn Manson
Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, Trevisan M, Black HR, Heckbert SR, Detrano R, Strickland OL, Wong ND, Crouse JR, Stein E, Cushman M, Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003 Aug 7;349(6):523-34.
Estrogen, Progestin, Coronary Heard DiseaseClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12904517https://www.whi.org/researchers/bibliography/Manuscripts/ms210.pdf
W1, W6
Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI).The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD).After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD.Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.
Publication
211
Effects of estrogen plus progestin on health-related quality of lifeJennifer Hays
Hays J, Ockene JK, Brunner RL, Kotchen JM, Manson JE, Patterson RE, Aragaki AK, Shumaker SA, Brzyski RG, LaCroix AZ, Granek IA, Valanis BG, Women's Health Initiative Investigators. Effects of estrogen plus progestin on health-related quality of life. N Engl J Med. 2003 May 8;348(19):1839-54. Epub 2003 Mar 17.
Health quality of life; menopause; estrogen plus progesterone; HRT; psychosocial; depression; cognition; mood; sleep; sexualityClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12642637https://www.whi.org/researchers/bibliography/Manuscripts/ms211.pdf
The Women's Health Initiative (WHI) and other clinical trials indicate that significant health risks are associated with combination hormone use. Less is known about the effect of hormone therapy on health-related quality of life.The WHI randomly assigned 16,608 postmenopausal women 50 to 79 years of age (mean, 63) with an intact uterus at base line to estrogen plus progestin (0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate, in 8506 women) or placebo (in 8102 women). Quality-of-life measures were collected at base line and at one year in all women and at three years in a subgroup of 1511 women.Randomization to estrogen plus progestin resulted in no significant effects on general health, vitality, mental health, depressive symptoms, or sexual satisfaction. The use of estrogen plus progestin was associated with a statistically significant but small and not clinically meaningful benefit in terms of sleep disturbance, physical functioning, and bodily pain after one year (the mean benefit in terms of sleep disturbance was 0.4 point on a 20-point scale, in terms of physical functioning 0.8 point on a 100-point scale, and in terms of pain 1.9 points on a 100-point scale). At three years, there were no significant benefits in terms of any quality-of-life outcomes. Among women 50 to 54 years of age with moderate-to-severe vasomotor symptoms at base line, estrogen and progestin improved vasomotor symptoms and resulted in a small benefit in terms of sleep disturbance but no benefit in terms of the other quality-of-life outcomes.In this trial in postmenopausal women, estrogen plus progestin did not have a clinically meaningful effect on health-related quality of life.
Publication
212
Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: Results from the Women's Health Initiative Hormone TrialKaren Margolis
Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, Bassford T, Burke G, Torrens J, Howard BV, Women's Health Initiative Investigators. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: Results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004 Jul;47(7):1175-87. Epub 2004 Jul 14.
diabetes mellitus, estrogen, progestin, cardiovascular diseases, breast cancer, fracturesClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15252707https://www.whi.org/researchers/bibliography/Manuscripts/ms212.pdf
Studies examining the effect of postmenopausal hormone therapy on concentrations of glucose, insulin and diabetes incidence have been inconclusive, in part because many of the studies were too small. We examined the effect of oestrogen plus progestin on diabetes incidence and insulin resistance.The study was a randomised, double-blind trial comparing the effect of daily 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up. The participants were 15,641 postmenopausal women enrolled in the Women's Health Initiative Hormone Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were measured in a random sample at baseline and at 1 and 3 years.The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2% in the placebo group (hazard ratio 0.79, 95% CI 0.67-0.93, p=0.004). There was little change in the hazard ratio after adjustment for changes in BMI and waist circumference. During the first year of follow-up, changes in fasting glucose and insulin indicated a significant fall in insulin resistance in actively treated women compared to the control subjects (Year 1 to baseline between-group difference -0.22+/-0.10, p=0.03). INTERPRETATIONS/CONCLUSION: These data suggest that combined therapy with oestrogen and progestin reduces the incidence of diabetes, possibly mediated by a decrease in insulin resistance unrelated to body size. Future studies of alternative postmenopausal hormone therapy regimens and selective oestrogen agonists and/or antagonists should consider the effects of these regimens on insulin resistance and diabetes.
Approved Manuscript
214
Selected psychosocial predictors of adherence to calcium/ vitamin D at the Women’s Health Initiative, Western New York Vanguard CenterShawn Lawrence
Adherence, Calcium/ Vitamin D, psychosocial, predictors, complianceClinical Trial
Publication
215
Influence of stressors on breast cancer incidence in the Women’s Health InitiativeYvonne Michael
Michael YL, Carlson NE, Chlebowski RT, Aickin M, Weihs KL, Ockene JK, Bowen DJ, Ritenbaugh C. Influence of stressors on breast cancer incidence in the Women’s Health Initiative. Health Psychol. 2009 Mar;28(2):137-146.
breast carcinoma, psychosocial stress, cancer screening, mammographyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19290705https://www.whi.org/researchers/bibliography/Manuscripts/ms215.pdf
To examine associations among life events stress, social support, and breast cancer incidence in a cohort of postmenopausal women. DESIGN AND MAIN OUTCOME MEASURE: Women's Health Initiative observational study participants, breast cancer free at entry, who provided assessment of stressful life events, social support, and breast cancer risk factors, were prospectively followed for breast cancer incidence (n = 84,334).During an average of 7.6 years of follow-up, 2,481 invasive breast cancers were diagnosed. In age-adjusted proportional hazards models, 1 stressful life event was associated with increased risk, but risk decreased with each additional stressful life event. After adjustment for confounders the decreasing risk was not significant. Stressful life events and social support appeared to interact in relation to breast cancer risk such that women who had greater number of stressful life events and low social support had a decreased risk of breast cancer.This study found no independent association between stressful life events and breast cancer risk. The results are compatible with a more complex model of psychosocial factors interacting in relation to breast cancer risk.
Publication
216
Effects of combination estrogen plus progestin hormone treatment on cognition and affectSusan Resnick
Resnick SM, Maki PM, Rapp SR, Espeland MA, Brunner R, Coker LH, Granek IA, Hogan P, Ockene JK, Shumaker SA, Women's Health Initiative Study of Cognitive Aging Investigators. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J Clin Endocrinol Metab. 2006 May;91(5):1802-10. Epub 2006 Mar 7.
Estrogen, HRT, Cognition, Memory, Mood, AffectClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16522699https://www.whi.org/researchers/bibliography/Manuscripts/ms216.pdf
AS103
Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory.The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women.This study was a randomized, double-blind, placebo-controlled clinical trial.Participants were women from 14 of 40 clinical centers of the Women's Health Initiative (WHI).Postmenopausal women (1416) aged 65 yr and older, free of probable dementia, and enrolled in WHI and the WHI Memory Study (WHIMS) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr, were studied.Intervention was conjugated equine estrogen (CEE; 0.625 mg) with 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet (CEE + MPA) or placebo.Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured.CEE + MPA had a negative impact on verbal memory (P <or= 0.01) and a trend to a positive impact on figural memory (P = 0.012) over time compared with placebo, but other cognitive domains were not affected. Both effects on memory were evident only after long-term therapy. CEE + MPA did not significantly influence positive affect, negative affect, or depressive symptoms.The effect of CEE + MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research.
Approved Proposal
217
Associations with gun-related threats and household fear in postmenopausal womenCharles Mouton
older women, guns, gun-related threatsObservational Study
Publication
218
Psychosocial effects of physical and verbal abuse in postmenopausal womenCharles Mouton
Mouton CP, Rodabough RJ, Rovi SL, Brzyski RG, Katerndahl DA. Psychosocial effects of physical and verbal abuse in postmenopausal women. Ann Fam Med. 2010 May-Jun;8(3):206-13
domestic violence; mental health; emotion well-beingObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/20458103https://www.whi.org/researchers/bibliography/Manuscripts/ms218.pdf
The purpose of this study was to examine the psychological effects of physical and verbal abuse in a cohort of older women.This observational cohort study was conducted at 40 clinical sites nationwide that are part of the Women's Health Initiative (WHI) Observational Study. We surveyed 93,676 women aged 50 to 79 years using the mental health subscales and the combined mental component summary (MCS) score of the RAND Medical Outcomes Study 36-item instrument.At baseline, women reporting exposure to physical abuse only, verbal abuse only, or both physical and verbal abuse had a greater number of depressive symptoms (1.6,1.6, and 3 more symptoms, respectively) and lower MCS scores (4.6, 5.4, and 8.1 lower scores, respectively) than women not reporting abuse. Compared with women who had no exposure to abuse, women had a greater increase in the number of depressive symptoms when they reported a 3-year incident exposure to physical abuse only (0.2; 95% confidence interval [CI], -0.21 to 0.60), verbal abuse only (0.18; 95% CI, 0.11 to 0.24), or both physical and verbal abuse (0.15; 95% CI, -0.05 to 0.36); and they had a decrease in MCS scores when they reported a 3-year incident exposure to physical abuse only (-1.12; 95% CI, -2.45 to 0.12), verbal abuse only (-0.55; 95% CI, -0.75 to -0.34), and both physical and verbal abuse (-0.44; 95% CI, -1.11 to -0.22) even after adjustment for sociodemographic characteristics.Exposure to abuse in older, functionally independent women is associated with poorer mental health. The persistence of these findings suggests that clinicians need to consider abuse exposure in their older female patients who have depressive symptoms. Clinicians caring for older women should identify women at risk for physical and verbal abuse and intervene appropriately.
Publication
220
The Women's Health Initiative: Implications for practiceKathleen Furniss
Furniss K. The Women's Health Initiative. Implications for practice. Adv Nurse Pract. 2002 Nov;10(11):53-5.
women's health, postmenopausal women, WHI, HRT, nurse practitionersClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12478949https://www.whi.org/researchers/bibliography/Manuscripts/ms220.pdf
Publication
221
Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: The Women's Health Initiative randomized trialGarnet Anderson
Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M, Liu J, McNeeley SG, Lopez AM, Women's Health Initiative Investigators. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: The Women's Health Initiative randomized trial. JAMA. 2003 Oct 1;290(13):1739-48.
gynecologic cancers, E+PClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/14519708https://www.whi.org/researchers/bibliography/Manuscripts/ms221.pdf
The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a randomized trial setting.To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures.Randomized, double-blind, placebo-controlled trial of 16 608 postmenopausal women, who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 (average follow-up, 5.6 years).One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).Incident invasive cancer of the ovary and endometrium.In 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer, 58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24). The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable differences were found in the distributions of tumor histology, stage, or grade for either cancer site. The incidence of other gynecologic cancers was low and did not differ by randomization assignment. More women taking estrogen plus progestin required endometrial biopsies (33% vs 6%; P<.001).This randomized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo. The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen. These data provide additional support for caution in the use of continuous combined hormones.
Publication
222
Estrogen plus progestin and risk of venous thrombosisMary Cushman
Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, Sidney S, Rosendaal FR, Women's Health Initiative Investigators. Estrogen plus progestin and risk of venous thrombosis. JAMA. 2004 Oct 6;292(13):1573-80
E+P, VTEClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15467059https://www.whi.org/researchers/bibliography/Manuscripts/ms222.pdf
W1, W6
Postmenopausal hormone therapy increases the risk of venous thrombosis. It is not known whether other factors influencing thrombosis add to this risk.To report final data on incidence of venous thrombosis in the Women's Health Initiative Estrogen Plus Progestin clinical trial and the association of hormone therapy with venous thrombosis in the setting of other thrombosis risk factors.Double-blind randomized controlled trial of 16,608 postmenopausal women between the ages of 50 and 79 years, who were enrolled in 1993 through 1998 at 40 US clinical centers with 5.6 years of follow up; and a nested case-control study. Baseline gene variants related to thrombosis risk were measured in the first 147 women who developed thrombosis and in 513 controls.Random assignment to 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate, or placebo.Centrally validated deep vein thrombosis and pulmonary embolus.Venous thrombosis occurred in 167 women taking estrogen plus progestin (3.5 per 1000 person-years) and in 76 taking placebo (1.7 per 1000 person-years); hazard ratio (HR), 2.06 (95% confidence interval [CI], 1.57-2.70). Compared with women between the ages of 50 and 59 years who were taking placebo, the risk associated with hormone therapy was higher with age: HR of 4.28 (95% CI, 2.38-7.72) for women aged 60 to 69 years and 7.46 (95% CI, 4.32-14.38) for women aged 70 to 79 years. Compared with women who were of normal weight and taking placebo, the risk associated with taking estrogen plus progestin was increased among overweight and obese women: HR of 3.80 (95% CI, 2.08-6.94) and 5.61 (95% CI, 3.12-10.11), respectively. Factor V Leiden enhanced the hormone-associated risk of thrombosis with a 6.69-fold increased risk compared with women in the placebo group without the mutation (95% CI, 3.09-14.49). Other genetic variants (prothrombin 20210A, methylenetetrahydrofolate reductase C677T, factor XIII Val34Leu, PAI-1 4G/5G, and factor V HR2) did not modify the association of hormone therapy with venous thrombosis.Estrogen plus progestin was associated with doubling the risk of venous thrombosis. Estrogen plus progestin therapy increased the risks associated with age, overweight or obesity, and factor V Leiden.
Approved Manuscript
223
Association of physical activity and fracture risk among postmenopausal womenMike LaMonte
fracture, physical activity, exercise, bone mineral density, osteoporosis, risk factorsObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms223.pdf
Publication
224
Estimation of dependence between paired correlated failure times in the presence of covariate measurement errorMalka Gorfine
Gorfine, Hsu, Prentice. Estimation of dependence between paired correlated failure times in the presence of covariate measurement error. J R Stat Soc [Ser B]. 2003;65(3):633-61.
Mismeaured covariates, Censored data, Bivariate survival model, Proportional hazards model, Replication data, Copula modelsObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms224.pdf
In many biomedical studies, covariates are subject to measurement error. Although it is well known that the regression coefficients estimators can be substantially biased if the measurement error is not accommodated, there has been little study of the effect of covariate measurement error on the estimation of the dependence between bivariate failure times. We show that the dependence parameter estimator in the Clayton–Oakes model can be considerably biased if the measurement error in the covariate is not accommodated. In contrast with the typical bias towards the null formarginal regression coefficients, the dependence parameter can be biased in either direction.We introduce a bias reduction technique for the bivariate survival function in copula models while assuming an additive measurement error model and replicated measurement for the covariates, and we study the large and small sample properties of the dependence parameter estimator proposed.
Publication
225
Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study:  A randomized controlled trialSally Shumaker
Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J, WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: A randomized controlled trial. JAMA. 2003 May 28;289(20):2651-62.
Estrogen, Progesterone, Dementia, Cognition, IncidenceClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12771112https://www.whi.org/researchers/bibliography/Manuscripts/ms225.pdf
AS39
Postmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy.To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo.The Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS.Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303).Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment.The mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia, 40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P =.01). This increased risk would result in an additional 23 cases of dementia per 10 000 women per year. Alzheimer disease was the most common classification of dementia in both study groups. Treatment effects on mild cognitive impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P =.72).Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older. In addition, estrogen plus progestin therapy did not prevent mild cognitive impairment in these women. These findings, coupled with previously reported WHI data, support the conclusion that the risks of estrogen plus progestin outweigh the benefits.
Publication
226
Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: A randomized controlled trialSteve Rapp
Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, Gass ML, Stefanick ML, Lane DS, Hays J, Johnson KC, Coker LH, Dailey M, Bowen D, WHIMS Investigators. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: A randomized controlled trial. JAMA. 2003 May 28;289(20):2663-72.
Estrogen, Progesterone, CognitionClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12771113https://www.whi.org/researchers/bibliography/Manuscripts/ms226.pdf
AS39
Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women.To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women.A randomized, double-blind, placebo-controlled clinical trial, WHIMS is an ancillary study of geographically diverse, community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995. Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline, 4532 (92.6%) were enrolled in the estrogen plus progestin component of WHIMS. A total of 4381 participants (96.7%) provided at least 1 valid cognitive function score between June 1995 and July 8, 2002.Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate (n = 2145) or matching placebo (n = 2236).Global cognitive function measured annually with the Modified Mini-Mental State Examination.The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time (mean follow-up of 4.2 years). Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo (P =.03), but these differences were not clinically important. Removing women by censoring them after adjudicated dementia, mild cognitive impairment, or stroke, and nonadherence to study protocol, did not alter the findings. Prior hormone therapy use and duration of prior use did not affect the interpretation of the results, nor did timing of prior hormone therapy initiation with respect to the final menstrual period. More women in the estrogen plus progestin group had a substantial and clinically important decline (> or =2 SDs) in Modified Mini-Mental State Examination total score (6.7%) compared with the placebo group (4.8%) (P =.008).Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo. While most women receiving estrogen plus progestin did not experience clinically relevant adverse effects on cognition compared with placebo, a small increased risk of clinically meaningful cognitive decline occurred in the estrogen plus progestin group.
Publication
229
Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health InitiativeVanessa Barnabei
Barnabei VM, Cochrane BB, Aragaki AK, Nygaard I, Williams RS, McGovern PG, Young RL, Wells EC, O'Sullivan MJ, Chen B, Schenken R, Johnson SR, Women's Health Initiative Investigators. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol. 2005 May;105(5 Pt 1):1063-73.
Estrogen, Progesterone, hormone therapy, gynecologic symptoms, vaginal bleeding, women’s Health InitiativeClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15863546https://www.whi.org/researchers/bibliography/Manuscripts/ms229.pdf
To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women.Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean +/- standard deviation 63.3 +/- 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out.Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04-3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24-1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27-1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001).Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.
Publication
230
Use of electric blankets and association with prevalence of endometrial cancerErnest Abel
Abel EL, Hendrix SL, McNeeley GS, O'Leary ES, Mossavar-Rahmani Y, Johnson SR, Kruger M. Use of electric blankets and association with prevalence of endometrial cancer. Eur J Cancer Prev. 2007 Jun;16(3):243-50.
electric blankets, electromagnetic fields, endometrial cancer, ethnicityObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17415095https://www.whi.org/researchers/bibliography/Manuscripts/ms230.pdf
The objective of this study was to assess the relationship between electric blanket use and prevalence of endometrial cancer for women. Information relating to women enrolled in the Women's Health Initiative Observational Data Set (n=93 676) used to test the relationship factors associated with endometrial cancer included older age at screening, younger age at last menstrual period, region of domicile (highest prevalence in the South), less than a high school education, lower income, body mass index >25 kg/m, low parity, unopposed use of estrogen, never use of estrogen plus progesterone, past alcohol use, higher percentage of daily calories from fat and any electric blanket use. Following a univariate identification of factors significantly related to endometrial cancer, stepwise logistic regression analysis was performed for those factors with P values of less than 0.001 in the univariate analysis. Using electric blankets was associated with a 15% higher prevalence of endometrial cancer than never having used electric blankets (odds ratio=1.15, 95% confidence interval: 1.03-1.27). After controlling for variables significantly associated with endometrial cancer, use of electric blankets for 20 years or more was associated with 36% higher prevalence of endometrial cancer (odds ratio=1.36, 95% confidence interval: 1.16-1.59). Although we were unable to determine the duration of electric blanket use before diagnosis of endometrial cancer, we found that women using electric blankets for 20 years or more had a significantly higher prevalence.
Publication
232
Women’s Health Initiative: Statistical aspects and selected early resultsRoss Prentice
Prentice R, Anderson G. Women’s Health Initiative:  Statistical aspects and selected early results. In: Armitage P, Colton T, eds. Encyclopedia of biostatistics. 2nd ed. Wiley,2005.
    chronic disease prevention;data management;data and safety monitoring;factorial design;quality assurance;randomized controlled trial;study power;women's healthBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/Ms232.pdf
An overview is provided of the women's health initiative clinical trial and observational study of 161 808 postmenopausal women in the age range 50 to 79. The clinical trial includes 68 132 women in a partial factorial design having four intervention comparisons: a low-fat eating pattern among 48 835 women; a hormone therapy trial of 0.625 mg per day of conjugated equine estrogen among 10 739 women who were posthysterectomy at baseline; a hormone therapy trial of this same estrogen plus 2.5 mg per day of medroxyprogesterone acetate among 16 608 women with uterus at baseline; and a calcium (1000 mg/day) plus vitamin D (400 international units/day) trial among 36 282 women. Each CT component had its specified primary and secondary hypotheses, along with an overriding emphasis on overall health benefits versus risks. A so-called global index was defined for each CT component as the earliest occurrence of a set of clinical outcomes plausibly affected by the intervention, or death from other causes. Specialized data management communication, quality assurance, and data monitoring procedures were established to support this large and complex research program. Some detail is provided on the results of the combined hormone trial component, which was stopped early in 2002 when the external Data and Safety Monitoring Board judged that overall health risks exceeded benefits over an average follow-up period in excess of five years.
Publication
233
Estrogen plus progestin and colorectal cancer in postmenopausal womenRowan Chlebowski
Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, Hubbell FA, Ascensao J, Rodabough RJ, Rosenberg CA, Taylor VM, Harris R, Chen C, Adams-Campbell LL, White E, Women's Health Initiative Investigators. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med. 2004 Mar 4;350(10):991-1004.
women's Health Initiative, Colorectal Cancer, Estrogen plus Progesterone, Clinical TrialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/14999111https://www.whi.org/researchers/bibliography/Manuscripts/ms233.pdf
Although the Women's Health Initiative (WHI) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer. We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants.In the WHI trial, 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were randomly assigned to a combination of conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The main outcome measures were the incidence, stages, and types of colorectal cancer, as determined by blinded central adjudication.There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group (hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.003). The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean +/-SD, 3.2+/-4.1 vs. 0.8+/-1.7; P=0.002) and were more advanced (regional or metastatic disease, 76.2 percent vs. 48.5 percent; P=0.004). In exploratory analyses, women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding (3.8+/-4.3 vs. 0.7+/-1.5 nodes, P=0.006).Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer. However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo.
Publication
234
Postmenopausal hormone therapy and body composition: A substudy of the estrogen plus progestin trial of the Women's Health InitiativeZhao Chen
Chen Z, Bassford T, Green SB, Cauley JA, Jackson RD, LaCroix AZ, Leboff M, Stefanick ML, Margolis KL. Postmenopausal hormone therapy and body composition--a substudy of the estrogen plus progestin trial of the Women's Health Initiative. Am J Clin Nutr. 2005 Sep;82(3):651-6.
Estrogen plus Progesterone, women's Health Initiative, Body CompositionClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16155280https://www.whi.org/researchers/bibliography/Manuscripts/ms234.pdf
It has been suggested that hormone therapy may help counter undesirable changes in body composition in older women.This study was designed to test whether estrogen plus progestin (E+P) therapy favorably affects age-related changes in body composition in postmenopausal women.The substudy was composed of 835 women from the estrogen plus progestin trial of the Women's Health Initiative who were randomly assigned to receive either E+P therapy (n = 437) or placebo (n = 398). The women had a mean age of 63.1 y and, on average, were 13.8 y past menopause. More than 17% of the participants were from an ethnic minority. No significant differences in baseline body composition (measured with dual-energy X-ray absorptiometry) by intervention assignment were observed.After 3 y of intervention, the women who received active E+P therapy lost less lean soft tissue mass (-0.04 kg) than did the women who received placebo (-0.44 kg; P = 0.001). Additionally, the women in the E+P group had less upper-body fat distribution than did the women in the placebo group (change in ratio of trunk to leg fat mass: -0.025 for the E+P group and 0.004 for the placebo group; P = 0.003). A sensitivity analysis, which was conducted on the women who took > or = 80% of the study medication during the intervention period, corroborated the findings from the intent-to-treat analysis.A 3-y E+P intervention significantly reduced both the loss of lean soft tissue mass and the ratio of trunk to leg fat mass in postmenopausal women. However, the effect sizes were small, and whether these changes in body composition lead to significant health benefits remains to be confirmed.
Publication
235
Hormone replacement therapy and risk of cardiovascular disease: Implications of the results of the Women's Health InitiativeLewis Kuller
Kuller LH. Women's Health Initiative. Hormone replacement therapy and risk of cardiovascular disease: Implications of the results of the Women's Health Initiative. Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):11-6.
E+P, CVDClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12524219https://www.whi.org/researchers/bibliography/Manuscripts/ms235.pdf
The higher rates of coronary heart disease (CHD), stroke, and venous thrombosis among women taking estrogen and progesterone (E+P) compared with placebo in the Women's Health Initiative clinical trial have important implications for women's health. Previous studies in both men and women have shown that estrogen therapy lowers low-density lipoprotein cholesterol and raises high-density lipoprotein cholesterol. The changes in these lipoproteins should be associated with at least a 30% decline in CHD risk. Estrogens increased very-low-density lipoprotein (VLDL) triglyceride levels and C-reactive protein. There is evidence that estrogens increase thrombin generation and fibrinolysis. The increase in VLDL triglycerides may enhance thrombotic risk as well as higher levels of atherogenic lipoproteins, such as dense low-density lipoprotein. Genetic variations in estrogen receptors and thrombosis or fibrinolysis may also be important in risks associated with E+P therapy. The increased risk of CHD and stroke with E+P therapy may be attributable to rise in VLDL triglycerides and thrombosis.
Publication
237
The Women’s Health Initiative Study of Cognitive Aging (WHISCA): A randomized clinical trial of the effects of hormone therapy on age-associated cognitive declineSusan Resnick
Resnick SM, Coker LH, Maki PM, Rapp SR, Espeland MA, Shumaker SA. The Women's Health Initiative Study of Cognitive Aging (WHISCA): A randomized clinical trial of the effects of hormone therapy on age-associated cognitive decline. Clin Trials. 2004;1(5):440-50.
Estrogen, Hormone Therapy, HRT, Cognition, Memory, Mood, AffectClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16279282https://www.whi.org/researchers/bibliography/Manuscripts/ms237.pdf
AS103
The Women's Health Initiative Study of Cognitive Aging (WHISCA) was a two armed, randomized, placebo controlled, clinical trial designed to assess the efficacy of postmenopausal hormone therapy on age related changes in specific cognitive functions. WHISCA was an ancillary study to the Women's Health Initiative (WHI) and the WHI Memory Study (WHIMS) and enrolled 2302 women aged 66 to 84 years (mean 73.9; standard deviation 3.8) who did not meet criteria for dementia. Women were randomly assigned by the WHI to hormone treatment (unopposed conjugated estrogens (CEE) 0.625 mg/day if they were without a uterus; CEE combined with medroxyprogesterone acetate (MPA) 2.5 mg/day otherwise) or placebo for an average of three years before the first WHISCA assessment. WHISCA investigated the effects of hormone therapy on rates of change over time in memory, other aspects of cognition (language, attention, spatial ability), motor function, and mood. In this paper, we present the study rationale and design, including specific cognitive measures, and the challenges of incorporating WHISCA into an ongoing randomized trial. WHISCA provided a unique opportunity to investigate the potential of hormone therapy to modify age related changes in specific cognitive functions. WHISCA also demonstrated the feasibility of adding a detailed cognitive assessment into an ongoing clinical trial to address an important issue in women's health, despite the challenges of maintaining the integrity of the parent studies, ensuring high retention, and achieving high quality assurance across sites.
Publication
240
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results From the Women's Health Initiative randomized controlled trialThe Writing Group for the WHI Investigators
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33
WHI, E+PClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/12117397https://www.whi.org/researchers/bibliography/Manuscripts/ms240.pdf
W1
Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Publication
242
Estrogen deficiency symptom management in breast cancer survivors in the changing context of menopausal hormone therapyRowan Chlebowski
Chlebowski RT, Kim JA, Col NF. Estrogen deficiency symptom management in breast cancer survivors in the changing context of menopausal hormone therapy. Semin Oncol. 2003 Dec;30(6):776-88
E+P, breast CancerClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/14663778https://www.whi.org/researchers/bibliography/Manuscripts/ms242.pdf
Vasomotor symptoms associated with menopause or cancer therapies represent an increasingly common problem for breast cancer survivors given the increasing use of ovarian suppression in premenopausal women and aromatase inhibitors in postmenopausal women. Although estrogen and/or progestin effectively reduce vasomotor symptoms, a recent Women's Health Initiative (WHI) randomized trial identified an unfavorable risk/benefit balance on life-threatening diseases, including increased breast cancer, for combined estrogen plus progestin use in otherwise healthy postmenopausal women. As a result, use of menopausal hormone therapy (MHT) for chronic disease risk reduction in any population cannot be supported. In addition, the safety of estrogen and/or progestin regarding risk of recurrence or new cancer development in breast cancer survivors has not been demonstrated. For vasomotor symptoms in this population, neuroendocrine agents, including selective seratonin reuptake inhibitors (SSRIs) or gabapentin, are reasonable choices with substantial impact on hot flashes and moderate toxicity profiles. When rigorously evaluated, most other nonhormonal pharmacologic and herbal interventions have been found to have either modest or no efficacy and/or limiting toxicity. In breast cancer survivors even local vulvar/vaginal symptoms are best treated by nonhormone products since drug absorption with systemic estrogen-like effects has been reported. Estrogen/progestin use in breast cancer survivors should be considered only for women with severe vasomotor symptoms refractory to other approaches after extensive informed decision-making including review of current Food and Drug Administration labeling concerns with use limited to the lowest dose and shortest duration possible.
Publication
243
Combined postmenopausal hormone therapy and cardiovascular disease: Toward resolving the discrepancy between observational studies and the Women’s Health Initiative clinical trialRoss Prentice
Prentice RL, Langer R, Stefanick ML, Howard BV, Pettinger M, Anderson G, Barad D, Curb JD, Kotchen J, Kuller L, Limacher M, Wactawski-Wende J, Women's Health Initiative Investigators. Combined postmenopausal hormone therapy and cardiovascular disease: Toward resolving the discrepancy between observational studies and the Women's Health Initiative clinical trial. Am J Epidemiol. 2005 Sep 1;162(5):404-14. Epub 2005 Jul 20.
HT, CHDClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16033876https://www.whi.org/researchers/bibliography/Manuscripts/ms243.pdf
Observational research on postmenopausal hormone therapy suggests a 40-50% reduction in coronary heart disease incidence among women using these preparations. In contrast, the Women's Health Initiative clinical trial of estrogen plus progestin found an elevated incidence over a 5.6-year intervention period through July 7, 2002. Toward explaining this discrepancy, the authors analyzed data from this trial, which included 16,608 postmenopausal women aged 50-79 years, and corresponding data from 53,054 women in the Women's Health Initiative observational study, 33% of whom were estrogen-plus-progestin users at baseline. Estrogen-plus-progestin hazard ratio estimates for coronary heart disease, stroke, and venous thromboembolism in the observational study were 39-48% lower than those in the clinical trial following age adjustment. However, hazard ratios tended to decrease with increasing time from initiation of estrogen-plus-progestin use, and observational study hazard ratio estimates are heavily weighted by longer-term use while clinical trial hazard ratio estimates reflect shorter-term use. Following control for time from estrogen-plus-progestin initiation and confounding, hazard ratio estimates were rather similar for the two cohorts, although there was evidence of some remaining difference for stroke. These analyses have implications for both the design and the analysis of observational studies.
Publication
245
Constipation and risk of cardiovascular disease among post-menopausal womenElena Salmoirago-Blotcher
Salmoirago-Blotcher E, Crawford S, Jackson E, Ockene J, Ockene I. Constipation and risk of cardiovascular disease among post-menopausal women. Am J Med. 2011 Aug;124(8):714-23. doi: 10.1016/j.amjmed.2011.03.026. Epub 2011 Jun 12.
constipation, depression, fiber, diet, exercise, ethnicity, urinary incontinenceObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/21663887https://www.whi.org/researchers/bibliography/Manuscripts/ms245.pdf
Constipation is common in Western societies, accounting for 2.5 million physician visits/year in the US. Because many factors predisposing to constipation also are risk factors for cardiovascular disease, we hypothesized that constipation may be associated with increased risk of cardiovascular events.We conducted a secondary analysis in 93,676 women enrolled in the observational arm of the Women's Health Initiative. Constipation was evaluated at baseline by a self-administered questionnaire. Estimates of the risk of cardiovascular events (cumulative end point including mortality from coronary heart disease, myocardial infarction, angina, coronary revascularization, stroke, and transient ischemic attack) were derived from Cox proportional hazards models adjusted for demographics, risk factors, and other clinical variables (median follow-up 6.9 years).The analysis included 73,047 women. Constipation was associated with increased age, African American and Hispanic descent, smoking, diabetes, high cholesterol, family history of myocardial infarction, hypertension, obesity, lower physical activity levels, lower fiber intake, and depression. Women with moderate and severe constipation experienced more cardiovascular events (14.2 and 19.1 events/1000 person-years, respectively) compared with women with no constipation (9.6/1000 person-years). After adjustment for demographics, risk factors, dietary factors, medications, frailty, and other psychological variables, constipation was no longer associated with an increased risk of cardiovascular events except for the severe constipation group, which had a 23% higher risk of cardiovascular events.In postmenopausal women, constipation is a marker for cardiovascular risk factors and increased cardiovascular risk. Because constipation is easily assessed, it may be a helpful tool to identify women with increased cardiovascular risk.
Publication
246
WHI response to Goodman, Goldzieher and Ayala's critique of the Women's Health Initiative report on the risks and benefits of estrogen plus progestinSusan Hendrix
Hendrix S, Prentice R. WHI response to Goodman, Goldzieher and Ayala's critique of the Women's Health Initiative report on the risks and benefits of estrogen plus progestin. Menopausal Medicine. 2003;11:1-4.
response, Goodman, Goldzieher, AyalaClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/ms246.pdf
Publication
248
Progression of coronary calcification in healthy postmenopausal womenJudith Hsia
Hsia J, Klouj A, Prasad A, Burt J, Adams-Campbell LL, Howard BV. Progression of coronary calcification in healthy postmenopausal women. BMC Cardiovasc Disord. 2004 Dec 1;4:21.
coronary calcificationObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15574196https://www.whi.org/researchers/bibliography/Manuscripts/ms248.pdf
Coronary artery calcium score incrementally improves coronary risk prediction beyond that provided by conventional risk factors. Limited information is available regarding rates of progression of coronary calcification in women, particularly those with baseline scores above zero. Further, determinants of progression of coronary artery calcification in women are not well understood. This study prospectively evaluated rates and determinants of progression of coronary artery calcium score in a group of healthy postmenopausal women.We determined coronary calcium score by computed tomography and recorded demographic, lifestyle and health characteristics of 914 postmenopausal women, a subset of those enrolled in the Women's Health Initiative Observational Study. The 305 women with calcium score >or=10 Agatston units at baseline were invited for repeat scan. This analysis includes the 94 women who underwent second scans.Mean age of study participants was 65 +/- 9 years (mean +/- SD), body mass index was 26.1 +/- 6.1 kg/m2, and baseline calcium score was 162 +/- 220 Agatston units. Mean interval between scans was 3.3 +/- 0.7 years. A wide range of changes in coronary calcium score was observed, from -53 to +452 Agatston units/year. Women with lower scores at baseline had smaller annual increases in absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston units/year among women with baseline calcium score in the lowest, middle and highest tertiles. In multivariate analysis, age was not an independent predictor of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use at baseline was a negative predictor (p = 0.015), whereas baseline calcium score was a strong, positive predictor (p < 0.0001) of progression of coronary calcification.Among postmenopausal women with coronary calcium score >or= 10 Agatston units, rates of change of coronary calcium score varied widely. In multivariate analysis, statin use was a negative independent determinant, whereas baseline calcium score was a strong positive predictor of annual change in coronary calcium score.
Publication
249
Effects of estrogen with and without progestin on urinary incontinenceSusan Hendrix
Hendrix SL, Cochrane BB, Nygaard IE, Handa VL, Barnabei VM, Iglesia C, Aragaki A, Naughton MJ, Wallace RB, McNeeley SG. Effects of estrogen with and without progestin on urinary incontinence. JAMA. 2005 Feb 23;293(8):935-48.
urinary incontinenceClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15728164https://www.whi.org/researchers/bibliography/Manuscripts/ms249.pdf
Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes, night sweats, and vaginal dryness, and it is often prescribed to treat urinary incontinence (UI).To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress, urge, and mixed UI in healthy postmenopausal women.Women's Health Initiative multicenter double-blind, placebo-controlled, randomized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998, for whom UI symptoms were known in 23,296 participants at baseline and 1 year.Women were randomized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin (E + P) or estrogen alone trials. The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (CEE + MPA); estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen (CEE). There were 8506 participants who received CEE + MPA (8102 who received placebo) and 5310 who received CEE alone (5429 who received placebo).Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline.Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline. The risk was highest for stress UI (CEE + MPA: relative risk [RR], 1.87 [95% confidence interval {CI}, 1.61-2.18]; CEE alone: RR, 2.15 [95% CI, 1.77-2.62]), followed by mixed UI (CEE + MPA: RR, 1.49 [95% CI, 1.10-2.01]; CEE alone: RR, 1.79 [95% CI, 1.26-2.53]). The combination of CEE + MPA had no significant effect on developing urge UI (RR, 1.15; 95% CI, 0.99-1.34), but CEE alone increased the risk (RR, 1.32; 95% CI, 1.10-1.58). Among women experiencing UI at baseline, frequency worsened in both trials (CEE + MPA: RR, 1.38 [95% CI, 1.28-1.49]; CEE alone: RR, 1.47 [95% CI, 1.35-1.61]). Amount of UI worsened at 1 year in both trials (CEE + MPA: RR, 1.20 [95% CI, 1.06-1.36]; CEE alone: RR, 1.59 [95% CI, 1.39-1.82]). Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities (CEE + MPA: RR, 1.18 [95% CI, 1.06-1.32]; CEE alone: RR, 1.29 [95% CI, 1.15-1.45]) and bothered or disturbed them (CEE + MPA: RR, 1.22 [95% CI, 1.13-1.32]; CEE alone: RR, 1.50 [95% CI, 1.37-1.65]) at 1 year.Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year. Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI.
Publication
250
Hormone therapy and age-related macular degeneration: The Women's Health Initiative Sight Exam StudyMary Haan
Haan MN, Klein R, Klein BE, Deng Y, Blythe LK, Seddon JM, Musch DC, Kuller LH, Hyman LG, Wallace RB. Hormone therapy and age-related macular degeneration: the Women's Health Initiative Sight Exam Study. Arch Ophthalmol. 2006 Jul;124(7):988-92.
Hormones, eye diseases, post-menopausal, Prempro, AMDClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16832022https://www.whi.org/researchers/bibliography/Manuscripts/ms250.pdf
AS62
To determine the effectiveness of treatment with conjugated equine estrogens (CEE) or with CEE combined with progestin (CEE + P) on age-related macular degeneration (AMD).In an ancillary study to the Women's Health Initiative clinical trial of hormone therapy, 4262 women 65 years and older underwent fundus photography for the determination of AMD. Participants were recruited from April 2000 to June 2002 at 21 clinical sites an average of 5 years after randomization. Participants were randomized to treatment with CEE, CEE + P, or placebo. Participants had been treated for an average of 5 years at the ophthalmic evaluation for AMD.The overall prevalence of any AMD was 21.0%. No association was found between CEE + P (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.75-1.11) or CEE alone (OR, 0.98; 95% CI, 0.78-1.25) and early-stage AMD. The CEE + P was associated with a reduced risk of soft drusen (OR, 0.83; 95% CI, 0.68-1.00) after adjustment for covariates and with a reduced risk of neovascular AMD (OR, 0.29; 95% CI, 0.09-0.92).Treatment with CEE alone or CEE + P does not affect early- or late-stage AMD. Treatment with CEE + P may reduce the risk of soft drusen or neovascular AMD.
Publication
253
Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women's Health Initiative Sight Exam ancillary studyRonald Klein
Klein R, Deng Y, Klein BE, Hyman L, Seddon J, Frank RN, Wallace RB, Hendrix SL, Kuppermann BD, Langer RD, Kuller L, Brunner R, Johnson KC, Thomas AM, Haan M. Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women's Health Initiative Sight Exam ancillary study. Am J Ophthalmol. 2007 Mar;143(3):473-83. Epub 2007 Jan 10.
eye diseases, post-menopausal, heart disease, HRT, visionClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17317391https://www.whi.org/researchers/bibliography/Manuscripts/ms253.pdf
AS62
To examine the association of cardiovascular disease (CVD), CVD risk factors, and CVD treatment with age-related macular degeneration (AMD).Observational analysis of a randomized clinical trial.The Women's Health Initiative Sight Examination (WHISE), an ancillary study to the Women's Health Initiative's clinical trial of hormone replacement therapy.A total of 4,288 women age 63 years and older.Information on CVD and its risk factors were obtained from a standardized questionnaire and examination.AMD as determined by standardized grading of fundus photographs.Prevalence of any AMD was 21.4% (n = 919). Of those with AMD, 5.8% (n = 53) had signs of exudative AMD (n = 39) or pure geographic atrophy (n = 14), limiting the power to examine associations. Significant associations between late AMD and CVD risk factors were (odds ratio [OR], 95% confidence interval [CI]) older age (1.19, 1.13 to 1.27, P < .0001), more pack years smoked (1.02 per pack-year smoked, 1.003 to 1.03, P = .01), systolic blood pressure (0.84 per 10 mm Hg, 0.71 to 0.995, P = .04), report of taking calcium channel blockers (2.49, 1.21 to 5.12, P = .04), self-reported history of diabetes (2.00, 1.01 to 3.96, P = .05), and greater body mass index (1.05 per 1 kg/m, 1.001 to 1.10, P = .05). History of myocardial infarction, stroke, use of statins, or white blood cell count was not associated with AMD.Results suggest that smoking, use of calcium channel blockers, diabetes, and obesity are risk factors for late AMD in women. However, the association of late AMD with systolic blood pressure and the effects of other CVD risk factors on early AMD need to be further explored.
Publication
265
Comparing SF-36 scores across three groups of women with different health profilesKathleen Yost
Yost KJ, Haan MN, Levine RA, Gold EB. Comparing SF-36 scores across three groups of women with different health profiles. Qual Life Res. 2005 Jun;14(5):1251-61.
quality of life, nutrition, health, behavior, psychosocial, questionnaires, SF-36 Scores, WHEL, WHI, HRQL, MOS, physical healthBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16047501https://www.whi.org/researchers/bibliography/Manuscripts/ms265.pdf
The widespread use of the Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36) facilitates the comparison of health-related quality of life (HRQL) across independent studies.To compare the scores of eight scales and two summary scales of the SF-36 across participants in the Women's Healthy Eating and Living (WHEL) trial, the Women's Health Initiative-Dietary Modification trial (WHI-DM), and the MOS, and to illustrate the use of effect sizes for interpreting the importance of group differences.WHEL and WHI-DM are both multi-center dietary interventions; only data from the UC Davis sites were used in our study. WHEL participants had a recent history of breast cancer, WHI-DM participants were healthy, postmenopausal women, and women in the MOS had a history of hypertension, diabetes, heart disease, or depression. General linear models were used to identify statistically significant differences in scale scores. Meaningful differences were determined by effect sizes computed using a common within-group standard deviation (SD) and SDs from normative data.After adjusting for age and marital status, SF-36 scores for the WHI-DM and WHEL samples were similar and both had statistically significantly higher scores than the MOS sample. Relative to the WHEL or WHI-DM studies, MOS scores for scales related to the physical domain were clearly meaningfully lower whereas scale scores related to the mental health domain were potentially meaningfully lower.The HRQL of breast cancer survivors is comparable to that of healthy women and better than that of women with chronic health conditions, particularly with respect to physical health. This study illustrated the use of ranges of effects sizes for aiding the interpretation of SF-36 scores differences across independent studies.
Approved Proposal
266
Correlation of endogenous sex steroid hormones with fasting glucose and insulin levels, HOMA indices, and incident diabetes mellitus in postmenopausal womenKathryn Rexrode
diabetes, glucose, insulin, endogenous sex steroid hormonesObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms266pv2.pdf
AS110
Publication
271
Factors associated with treatment initiation after osteoporosis screeningRenee Brennan
Brennan RM, Wactawski-Wende J, Crespo CJ, Dmochowski J. Factors associated with treatment initiation after osteoporosis screening. Am J Epidemiol. 2004 Sep 1;160(5):475-83.
osteoporosisClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15321845https://www.whi.org/researchers/bibliography/Manuscripts/ms271.pdf
AS98
The prevalence of osteoporosis and factors associated with treatment initiation after detection of osteoporosis were determined for previously unscreened, postmenopausal women. Dual-energy x-ray absorptiometry screening was conducted in 1997-2000 as part of an ancillary study of the Buffalo, New York, center of the Women's Health Initiative Observational Study. A total of 945 women were previously unaware of their bone density, although, for 344 (36.4%), osteoporosis was newly detected through screening (T-score </= -2.5). Of those women, 250 (72.7%) discussed the results with a health care provider, and 140 (56.0%) initiated treatment after doing so. In multivariate logistic regression analyses, factors associated with treatment initiation were T-score (odds ratio (OR) = 0.39 per unit increase, 95% confidence interval (CI): 0.23, 0.67), routine medical care more often than yearly (OR = 2.08, 95% CI: 1.12, 3.86), college education (OR = 2.58, 95% CI: 1.25, 5.31), family income of >/=$50,000 (OR = 2.06, 95% CI: 1.03, 4.14), and discussing screening results with a gynecologist (OR = 3.20, 95% CI: 1.33, 7.67). These findings suggest that many postmenopausal women are unaware of their bone density and could benefit from screening. In this study, approximately half of the women with osteoporosis initiated treatment after screening. Disease severity, medical care frequency, education, income, and physician type predicted treatment initiation.
Publication
272
Effect of estrogen therapy on gallbladder diseaseDominic Cirillo
Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix AZ, Limacher MC, Larson JC. Effect of estrogen therapy on gallbladder disease. JAMA. 2005 Jan 19;293(3):330-9.
gallbladder disease, cholelithiasis, cholecystectomy, estrogen, HRT, NSAID, aspirin, statins, risk factorsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15657326https://www.whi.org/researchers/bibliography/Manuscripts/ms272.pdf
Estrogen therapy is thought to promote gallstone formation and cholecystitis but most data derive from observational studies rather than randomized trials.To determine the effect of estrogen therapy in healthy postmenopausal women on gallbladder disease outcomes.Two randomized, double-blind, placebo-controlled trials conducted at 40 US clinical centers. The volunteer sample was 22,579 community-dwelling women aged 50 to 79 years without prior cholecystectomy.Women with hysterectomy were randomized to 0.625 mg/d of conjugated equine estrogens (CEE) or placebo (n = 8376). Women without hysterectomy were randomized to estrogen plus progestin (E + P), given as CEE plus 2.5 mg/d of medroxyprogesterone acetate (n = 14,203).Participants reported hospitalizations for gallbladder diseases and gallbladder-related procedures, with events ascertained through medical record review. Cox proportional hazards regression was used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) using intention-to-treat and time-to-event methods.The CEE and the E + P groups were similar to their respective placebo groups at baseline. The mean follow-up times were 7.1 years and 5.6 years for the CEE and the E + P trials, respectively. The annual incidence rate for any gallbladder event was 78 events per 10,000 person-years for the CEE group (vs 47/10,000 person-years for placebo) and 55 per 10,000 person-years for E + P (vs 35/10,000 person-years for placebo). Both trials showed greater risk of any gallbladder disease or surgery with estrogen (CEE: HR, 1.67; 95% CI, 1.35-2.06; E + P: HR, 1.59; 95% CI, 1.28-1.97). Both trials indicated a higher risk for cholecystitis (CEE: HR, 1.80; 95% CI, 1.42-2.28; E + P: HR, 1.54; 95% CI 1.22-1.94); and for cholelithiasis (CEE: HR, 1.86; 95% CI, 1.48-2.35; E + P: HR, 1.68; 95% CI, 1.34-2.11) for estrogen users. Also, women undergoing estrogen therapy were more likely to receive cholecystectomy (CEE: HR, 1.93; 95% CI, 1.52-2.44; E + P: HR, 1.67; 95% CI, 1.32-2.11), but not other biliary tract surgery (CEE: HR, 1.18; 95% CI, 0.68-2.04; E + P: HR, 1.49; 95% CI, 0.78-2.84).These data suggest an increase in risk of biliary tract disease among postmenopausal women using estrogen therapy. The morbidity and cost associated with these outcomes may need to be considered in decisions regarding the use of estrogen therapy.
Publication
273
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. The Women’s Health Initiative randomized controlled trialGarnet Anderson
Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S, Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12.
estrogen, hormone replacement therapy; postmenopausal; primary prevention; cardiovascular disease; cancer; fractures, women’s Health InitiativeClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15082697https://www.whi.org/researchers/bibliography/Manuscripts/ms273.pdf
W1, W6
Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.
Publication
274
Association between reported alcohol intake and cognition: Results from the Women's Health Initiative Memory StudyMark Espeland
Espeland MA, Gu L, Masaki KH, Langer RD, Coker LH, Stefanick ML, Ockene J, Rapp SR. Association between reported alcohol intake and cognition: results from the Women's Health Initiative Memory Study. Am J Epidemiol. 2005 Feb 1;161(3):228-38.
WHIMS, alcohol intake, cognitionClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15671255https://www.whi.org/researchers/bibliography/Manuscripts/ms274.pdf
AS39
Some, but not all, observational studies have suggested that moderate levels of alcohol intake may be associated with improved cognitive function and reduced risk of cognitive decline and dementia. The authors of this 1996-2002 study used data from the Women's Health Initiative Memory Study of postmenopausal combination hormone therapy to assess cross-sectional and prospective associations of self-reported alcohol intake with cognitive function. Across 39 US academic medical centers, 4,461 community-dwelling women aged 65-79 years were followed an average of 4.2 years with annual Modified Mini-Mental State Examinations and standardized protocols for detecting mild cognitive impairment and probable dementia. Compared with no intake, intake of > or =1 drink per day was associated with higher baseline Modified Mini-Mental State Examination scores (p < 0.001) and a covariate-adjusted odds ratio of 0.40 (95% confidence interval: 0.28, 0.99) for significant declines in cognitive function. Associations with incident probable dementia and mild cognitive impairment were of similar magnitude but were not statistically significant after covariate adjustment. Associations with intakes of <1 drink per day were intermediate. Moderate levels of alcohol intake may be associated with better cognition and reduced risk of significant cognitive decline; however, confounding associations with unmeasured factors cannot be ruled out.
Approved Proposal
276
Social support and cognitive functioning in post-menopausal womenCatherine Messina
post-menopausal women; mental health; cognitive functioning; social support; social relationships; social burdenMemory Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms276pv2.pdf
AS39
Publication
277
Estrogen plus progestin and the risk of peripheral arterial disease: The Women's Health InitiativeJudith Hsia
Hsia J, Criqui MH, Rodabough RJ, Langer RD, Resnick HE, Phillips LS, Allison M, Bonds DE, Masaki K, Caralis P, Kotchen JM, Women's Health Initiative Investigators. Estrogen plus progestin and the risk of peripheral arterial disease: the Women's Health Initiative. Circulation. 2004 Feb 10;109(5):620-6.
E+P, PADClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/14769684https://www.whi.org/researchers/bibliography/Manuscripts/ms277.pdf
Observational studies have reported less frequent carotid atherosclerosis in healthy women taking postmenopausal hormone therapy. Estrogen with progestin did not reduce peripheral arterial events among women with preexisting coronary heart disease. This analysis evaluates clinical peripheral arterial disease among generally healthy women in the Women's Health Initiative randomized trial of estrogen plus progestin.The Estrogen Plus Progestin trial assigned 16 608 postmenopausal women, mean age 63.3+/-7.1 years, to daily conjugated estrogens (0.625 mg) with medroxyprogesterone acetate (2.5 mg) or placebo and documented health outcomes over an average of 5.6 years of follow-up. Hospitalization for peripheral arterial disease was infrequent, with annualized rates of 0.08%, 0.06%, and 0.02% for carotid disease, lower extremity arterial disease, and abdominal aortic aneurysm, respectively. The incidence of peripheral arterial events did not differ between treatment groups (hazard ratio [HR] 0.89, 95% confidence interval 0.63, 1.25). The risk was slightly greater among women assigned to active estrogen with progestin in years 1 (HR 1.33) and 2 (HR 1.27), and was slightly lower in later years (HR 0.85 and 0.87 in years 5 and > or =6). Among adherent participants, the hazard ratio for peripheral arterial events was 1.23 (95% confidence interval 0.79, 1.91) over the 5.6 years of follow up. Subgroup analysis identified no significant interactions between estrogen with progestin and baseline characteristics with regard to peripheral arterial disease risk.Among generally healthy postmenopausal women, conjugated estrogens with progestin did not confer protection against peripheral arterial disease.
Publication
279
Symptom experience after discontinuing use of estrogen plus progestinJudith Ockene
Ockene JK, Barad DH, Cochrane BB, Larson JC, Gass M, Wassertheil-Smoller S, Manson JE, Barnabei VM, Lane DS, Brzyski RG, Rosal MC, Wylie-Rosett J, Hays J. Symptom experience after discontinuing use of estrogen plus progestin. JAMA. 2005 Jul 13;294(2):183-93.
E+P, symptoms, managementClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16014592https://www.whi.org/researchers/bibliography/Manuscripts/ms279.pdf
Little is known about women's experiences after stopping menopausal hormone therapy.To describe women's symptoms and management strategies after stopping the intervention in a large estrogen plus progestin trial.Cross-sectional survey of 8405 women (89.9%; N = 9351) at 40 clinical centers who were still taking study pills (conjugated equine estrogens plus medroxyprogesterone [CEE + MPA] or placebo) when the estrogen plus progestin intervention (Women's Health Initiative) was stopped. Surveys were mailed 8 to 12 months after the stop date. Logistic regression was used to model vasomotor symptoms and pain or stiffness symptoms as functions of former treatment and baseline symptoms, adjusted for appropriate covariates.Symptoms (vasomotor or pain and stiffness) and management strategies.Respondents' mean (SD) age at trial stop date was 69.1 (6.7) years. They averaged 5.7 years of taking study pills. Moderate or severe vasomotor symptoms after discontinuing study pill use were reported by 21.2% of former CEE + MPA and 4.8% of placebo group respondents overall and by 55.5% and 21.3%, respectively, with these symptoms at baseline (randomization). Compared with respondents in the former placebo group, moderate or severe vasomotor symptoms (adjusted odds ratio [AOR] 5.82; 95% confidence interval [CI], 4.92-6.89) and pain or stiffness symptoms (AOR, 2.16; 95% CI, 1.95-2.40) were more likely in respondents in the former CEE + MPA group. Both vasomotor symptoms (AOR, 5.36; 95% CI, 4.51-6.38) and pain or stiffness symptoms (AOR, 3.21; 95% CI, 2.90-3.56) also were more likely in women with these symptoms at baseline. Women reported a wide range of strategies to manage symptoms.More than half of the women with vasomotor symptoms at randomization to active CEE + MPA also reported these symptoms after discontinuing use of the study pills. However, these participants did not include women who were unwilling to be randomized or who had stopped taking the study pills earlier. These findings should be considered when advising women to treat menopausal symptoms with hormone therapy for as short duration as possible. Investigation of alternative strategies to manage menopausal symptoms is warranted.
Publication
280
Relation of BMI and physical activity to sex hormones in postmenopausal womenAnne McTiernan
McTiernan A, Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modugno F, Perri MG, Stanczyk FZ, Van Horn L, Wang CY, Women's Health Initiative Investigators. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring). 2006 Sep;14(9):1662-77.
diet, activityClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17030978https://www.whi.org/researchers/bibliography/Manuscripts/ms280.pdf
W5
Levels of estrogen, androgen, and prolactin have been related to risk of postmenopausal breast cancer. However, the determinants of these hormone concentrations are not established. The purpose of this study was to examine correlates of endogenous sex hormones.Associations among adiposity, physical activity, and diet and concentrations of estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone-binding globulin (SHBG), androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and prolactin were evaluated in 267 postmenopausal women randomly selected from the Women's Health Initiative Dietary Modification Trial.In multiple regression analyses on log-transformed hormones, BMI was positively associated with estrone (beta = 0.031, p < 0.001), estradiol (beta = 0.048, p < 0.001), free estradiol (beta = 0.062, p < 0.001), free testosterone (beta = 0.017, p = 0.02), and prolactin (beta = 0.012, p = 0.02) and negatively associated with SHBG (beta = -0.02, p = 0.001). Total physical activity (metabolic equivalent tasks per week) was negatively associated with concentrations of estrone, estradiol, and androstenedione (beta = -0.006, -0.007, and -0.005, respectively, all p < or = 0.05). Using a composite variable of BMI and physical activity dichotomized by median values, women with high BMI/low physical activity had a mean estrone concentration of 28.8 pg/mL, compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical activity, low BMI/low physical activity, and low BMI/high physical activity, respectively (p trend < 0.001). Similar trends were observed for estradiol and free estradiol and, in inverse, for SHBG.These associations may, in part, explain the positive associations between overweight/obesity and a sedentary lifestyle on breast cancer risk.
Publication
282
Improving dietary self-monitoring and adherence with hand-held computers: A pilot studyKaren Glanz
Glanz K, Murphy S, Moylan J, Evensen D, Curb JD. Improving dietary self-monitoring and adherence with hand-held computers: A pilot study. Am J Health Promot. 2006 Jan-Feb;20(3):165-70.
Personal Digital Assistants, Dietary AdherenceClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16422134https://www.whi.org/researchers/bibliography/Manuscripts/ms282.pdf
Innovations in information technology offer new opportunities for creative application of personalized, tailored feedback strategies for improving dietary adherence. We developed and tested a real-time diet-monitoring and feedback system using hand-held computers. The goals were to increase diet self-monitoring, reduce the burden of monitoring food intake, and increase adherence to dietary goals within a clinical trial.Participants were 33 women in the Diet Modification arm of the Women's Health Initiative (WHI). After using focus groups to determine system features, women used the Personal Digital Assistant (PDA)-based system for 1 month and received immediate and weekly tailored feedback. The process and outcomes were evaluated using real-time food records collected through the PDAs; surveys; and self-reported food frequency questionnaires.Participants significantly increased self-monitoring, improved their attitudes toward self-monitoring, and met their dietary goals more often. Reported total fat intake and percent energy from fat decreased significantly. There was a modest decrease in mean caloric intake.The pilot study findings support the largely untapped potential of hand-held computers for improving diet monitoring and diet adherence, particularly within a clinical trial.
Publication
285
Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's Health Initiative randomized trialAnne McTiernan
McTiernan A, Martin CF, Peck JD, Aragaki AK, Chlebowski RT, Pisano ED, Wang CY, Brunner RL, Johnson KC, Manson JE, Lewis CE, Kotchen JM, Hulka BS, Women's Health Initiative Mammogram Density Study Investigators. Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's Health Initiative randomized trial. J Natl Cancer Inst. 2005 Sep 21;97(18):1366-76.
E+P, mammogramClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16174858https://www.whi.org/researchers/bibliography/Manuscripts/ms285.pdf
AS36
Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density.In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models.Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P < .001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P < .001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P < .001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density.Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.
Publication
287
Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestinGarnet Anderson
Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, Aggerwal A, Curb JD, Hendrix SL, Allan Hubbell F, Khandekar J, Lane DS, Lasser N, Lopez AM, Potter J, Ritenbaugh C. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas. 2006 Sep 20;55(2):103-15. Epub 2006 Jul 11.
risk factors, estrogen plus progestin, incident breast cancers, abnormal mammogramsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16815651https://www.whi.org/researchers/bibliography/Manuscripts/ms287.pdf
To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women's Health Initiative (WHI) randomized trial.Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up.Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors.A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.
Publication
288
Insulin, physical activity, and caloric intake in postmenopausal women: Breast cancer implicationsRowan Chlebowski
Chlebowski RT, Pettinger M, Stefanick ML, Howard BV, Mossavar-Rahmani Y, McTiernan A. Insulin, physical activity, and caloric intake in postmenopausal women: Breast cancer implications. J Clin Oncol. 2004 Nov 15;22(22):4507-13.
physical activity, breast cancer, energy intakeBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15542801https://www.whi.org/researchers/bibliography/Manuscripts/ms288.pdf
Increased physical activity and programs to reduce body mass index (BMI) with both increased physical activity and decreased caloric intake have been proposed to reduce insulin as a potential mediator of breast cancer and other chronic diseases. However, there are few data on the relative contribution of physical activity, caloric intake, and BMI to fasting insulin levels.An ethnically diverse subsample of 2,996 mostly healthy postmenopausal women with no prior cancer history was randomly identified from the 161,809 participants in the Women's Health Initiative clinical trials and observational study. Information was collected on diet, recreational physical activity, and anthropometrics including BMI. Fasting insulin levels were determined. Using a cross-sectional design, insulin levels were then compared across quintiles of caloric intake and physical activity in linear regression model analyses controlled for BMI and other factors.Lower BMI (P < .0001), higher levels of physical activity (P < .0001), and lower caloric intake (P < .02) were all independently associated with significantly lower mean fasting insulin levels throughout the range of observed values. Insulin levels of 8.74 microU/mL +/- 4.16 SD were seen in the highest physical activity and lowest caloric intake quintile compared with insulin levels of 15.08 microU/mL +/- 16.32 SD in the lowest physical activity and highest caloric intake quintile (P < .0001).These findings suggest that reduction in BMI achieved by increasing physical activity, reducing caloric intake, or both, should lower insulin levels, providing support for clinical trials evaluating insulin level change and breast cancer risk.
Publication
289
Cutaneous melanoma in postmenopausal women following nonmelanoma skin carcinoma: The Women's Health Initiative Observational StudyCarol Rosenberg
Rosenberg CA, Khandekar J, Greenland P, Rodabough RJ, McTiernan A. Cutaneous melanoma in postmenopausal women after nonmelanoma skin carcinoma: The Women's Health Initiative Observational Study. Cancer. 2006 Feb 1;106(3):654-63.
Cancer, nonmelanoma skin cancer, skin cancer, and risk of second malignancyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16365851https://www.whi.org/researchers/bibliography/Manuscripts/ms289.pdf
An elevated risk for cutaneous melanoma has been reported in individuals with nonmelanoma skin carcinoma (NMSC), but to the authors' knowledge, this association has not been prospectively studied in a large, multigeographic population of postmenopausal women.The association between NMSC and the incidence of cutaneous melanoma was assessed in the Women's Health Initiative Observational Study involving 67,030 non-Hispanic white postmenopausal women ages 50-79 years and who were free of prior other cancers at baseline. Cancer history, demographics, and previous and current risk exposures were determined by questionnaires at baseline and follow-up. Participants' reports of incident cutaneous melanoma collected annually were confirmed by physician review of medical records. Cox proportional hazards analyses were used to assess the relation of prior NMSC with incident cutaneous melanoma.In age-adjusted analysis, women with a history of NMSC but no other malignancy (n = 5552) were found to be 2.41 times more likely to develop cutaneous melanoma over a mean 6.5 years compared with women who had no history of NMSC (95% confidence interval [95% CI], 1.82-3.20). In a multivariate analysis, women with a history of NMSC and no other cancer history at baseline were 1.70 times more likely to develop cutaneous melanoma compared with women without NMSC (95% CI, 1.18-2.44).The results of the current study provide evidence and further defines the magnitude of increased risk for cutaneous melanoma in postmenopausal non-Hispanic white women with a history of NMSC.
Publication
292
Menopausal hormone therapy informed consentSusan Hendrix
Hendrix SL. Menopausal hormone therapy informed consent. Am J Obstet Gynecol. 2003 Oct;189(4 Suppl):S31-2; discussion S32-6.
none providedBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14586317https://www.whi.org/researchers/bibliography/Manuscripts/ms292.pdf
Approved Manuscript
293
Effect of airborne particulate matter and other air pollutants on the incidence of cardiovascular events in the WHI OSJoel Kaufman
Observational Study
Publication
294
Weighted estimators for proportional hazards regression with missing covariatesLihong Qi
Qi L, Wang CY, Prentice RL.  Weighted estimators for proportional hazards regression with missing covariates. J Am Stat Assoc. 2005;100:1250-1263.
disease prevention trials, clinical trials, statistical methods,  Cox proportional hazards model, weighted estimatorsObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/Ms294.pdf
Publication
298
The association between aspirin use and the incidence of colorectal cancer in womenMatthew Allison
Allison M, Garland C, Chlebowski R, Criqui M, Langer R, Wu L, Roy H, McTiernan A, Kuller L, Women's Health Initiative Investigators. The association between aspirin use and the incidence of colorectal cancer in women. Am J Epidemiol. 2006 Sep 15;164(6):567-75. Epub 2006 Jul 17
Colorectal cancer, aspirin, chemoprevention, prevention, cohort studyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16847042https://www.whi.org/researchers/bibliography/Manuscripts/ms298.pdf
The purpose of this study was to test the hypothesis that aspirin use is associated with a decreased risk of incident colorectal cancer. From the Women's Health Initiative, 91,574 participants between the ages of 50 and 79 years at baseline in 1993-1998 provided details on aspirin use via interview using a standardized questionnaire and were subsequently followed annually for incident colorectal cancer during a period of over 6 years. For those persons who reported aspirin use, the type of compound, dose, and duration of use were recorded. Medical histories suggestive of colorectal cancers at the annual update were verified by medical record and pathology report review by trained local physician adjudicators. There were 631 confirmed cases of invasive cancer of the colon or rectum. There was no significant association between any aspirin use and risk for incident colorectal cancer (hazard ratio = 0.96, 95% confidence interval: 0.8, 1.2). Moreover, with no aspirin use as the referent category, there were no significant associations for duration of aspirin intake by category (< 1, 1- < 2, 2- < 3, 3- < 4, 4- < 5, and > or = 5 years) or for daily dosage by category (< 165, 165- < 300, 300- < 495, or > or = 495 mg).
Publication
301
Angiotensin-converting enzyme inhibitor use and incident frailty in women aged 65 and older: prospective findings from the Women's Health Initiative Observational StudyShelly Gray
Gray SL, LaCroix AZ, Aragaki AK, McDermott M, Cochrane BB, Kooperberg CL, Murray AM, Rodriguez B, Black H, Woods NF; Women's Health Initiative Observational Study. Angiotensin-converting enzyme inhibitor use and incident frailty in women aged 65 and older: prospective findings from the Women's Health Initiative Observational Study. J Am Geriatr Soc. 2009 Feb;57(2):297-303.
ACE inhibitor use, frailty, disability, Women’s Health InitiativeBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/19207145https://www.whi.org/researchers/bibliography/Manuscripts/ms301.pdf
AS179
To examine the associations between current use, duration, and potency of angiotensin-converting enzyme (ACE) inhibitors and incident frailty in women aged 65 and older who were not frail at baseline.Data were from the Women's Health Initiative Observational Study (WHI-OS), a prospective study conducted at 40 U.S. clinical centers.Women aged 65 to 79 at baseline who were not frail (N=27,378).Current ACE inhibitor use was ascertained through direct inspection of medicine containers at baseline. Components of frailty were self-reported low physical function or impaired walking, exhaustion, low physical activity, and unintended weight. Frailty was ascertained through self-reported and physical measurements data at baseline and 3-year clinic contacts.By the 3-year follow-up, 3,950 (14.4%) women had developed frailty. Current ACE inhibitor use had no association with incident frailty (multivariate adjusted odds ratio=0.96, 95% confidence interval=0.82-1.13). Duration and potency of ACE inhibitor use were also not significantly associated with incident frailty. A similar pattern of results was observed when incident cardiovascular disease events were studied as a separate outcome or when the sample was restricted to subjects with hypertension.Overall, incidence of frailty was similar in current ACE inhibitor users and nonusers.
Publication
302
Frailty: Emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational StudyNancy Woods
Woods NF, LaCroix AZ, Gray SL, Aragaki A, Cochrane BB, Brunner RL, Masaki K, Murray A, Newman AB. Frailty: Emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study. J Am Geriatr Soc. 2005 Aug;53(8):1321-30.
Frailty, activities of daily living, ethnicity, disabilityBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16078957https://www.whi.org/researchers/bibliography/Manuscripts/Ms302.pdf
AS179
To define frailty using simple indicators; to identify risk factors for frailty as targets for prevention; and to investigate the predictive validity of this frailty classification for death, hospitalization, hip fracture, and activity of daily living (ADL) disability.Prospective study, the Women's Health Initiative Observational Study.Forty U.S. clinical centers.Forty thousand six hundred fifty-seven women aged 65 to 79 at baseline.Components of frailty included self-reported muscle weakness/impaired walking, exhaustion, low physical activity, and unintended weight loss between baseline and 3 years of follow-up. Death, hip fractures, ADL disability, and hospitalizations were ascertained during an average of 5.9 years of follow-up.Baseline frailty was classified in 16.3% of participants, and incident frailty at 3-years was 14.8%. Older age, chronic conditions, smoking, and depressive symptom score were positively associated with incident frailty, whereas income, moderate alcohol use, living alone, and self-reported health were inversely associated. Being underweight, overweight, or obese all carried significantly higher risk of frailty than normal weight. Baseline frailty independently predicted risk of death (hazard ratio (HR)=1.71, 95% confidence interval (CI)=1.48-1.97), hip fracture (HR=1.57, 95% CI=1.11-2.20), ADL disability (odds ratio (OR)=3.15, 95% CI=2.47-4.02), and hospitalizations (OR=1.95, 95% CI=1.72-2.22) after adjustment for demographic characteristics, health behaviors, disability, and comorbid conditions.These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women. Underweight, obesity, smoking, and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention.
Publication
303
Statin use and incident frailty in women aged 65 years or older: Prospective findings from the Women's Health Initiative Observational StudyAndrea LaCroix
Lacroix AZ, Gray SL, Aragaki A, Cochrane BB, Newman AB, Kooperberg CL, Black H, Curb JD, Greenland P, Woods NF. Statin use and incident frailty in women aged 65 years or older: Prospective findings from the Women's Health Initiative Observational Study. J Gerontol A Biol Sci Med Sci. 2008 Apr;63(4):369-75.
Frailty, Statin, physical performance, disabilityBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18426960https://www.whi.org/researchers/bibliography/Manuscripts/ms303.pdf
AS179
Inflammatory biomarkers have shown consistent associations with disability and frailty in older adults. Statin medications may reduce the incidence the frailty because of their anti-inflammatory effects. This study examines associations between current use, duration, and potency of statin medications and incident frailty in initially nonfrail women 65 years old or older.The authors conducted a prospective analysis of data from the Women's Health Initiative Observational Study (WHI-OS) conducted at 40 clinical centers in the United States. Eligible women were nonfrail and 65-79 years old at baseline (n = 25,378). Current statin use at baseline was ascertained through direct inspection of medicine containers during clinic visits. Frailty was ascertained through self-reported indicators and physical measurements at baseline and 3-year clinic contacts. Components of frailty included self-reported low physical function, exhaustion, low physical activity, and unintended weight loss. Multinomial logistic regression models were used to adjust for covariates predicting incident frailty.Among the 25,378 eligible women, 3453 (13.6%) developed frailty by the 3-year follow-up contact. Current statin use had no association with incident frailty (multivariate-adjusted odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.85-1.16). Duration and potency of statin use were also not significantly associated with incident frailty. Among low potency statin users, longer duration of use was associated with reduced risk of frailty (p for trend =.02). A similar pattern of results was observed when frailty was studied in the absence of intervening, incident cardiovascular events.Overall, incidence of frailty was similar in current statin users and nonusers.
Publication
304
No increase in fractures after stopping hormone therapy: results from the Women's Health InitiativeNelson Watts
Watts NB, Cauley JA, Jackson RD, LaCroix AZ, Lewis CE, Manson JE, Neuner J, Phillips LS, Stefanick ML, Wactawski-Wende J, Crandall C; Women’s Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017 Jan 1;102(1):302-308. doi: 10.1210/jc.2016-3270.
Women’s health Initiative, estrogen, progestin, hormone therapy, discontinuation, fracture, post menopause, conjugated equine estrogens, medroxyprogesterone acetateBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/27820659https://www.whi.org/researchers/bibliography/Manuscripts/ms304.pdf
CONTEXT: The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures but a later observational report suggested loss of benefit and a rebound increased risk after stopping. OBJECTIVE: To examine fractures after discontinuation of HT Design and Setting: Two placebo-controlled randomized trials Patients: 15,187 WHI participants who continued active HT or placebo through the intervention period and did not take HT in the post-intervention period Interventions: Conjugated equine estrogen + medroxyprogesterone acetate (CEE+MPA) in naturally menopausal women and conjugated equine estrogen (CEE) alone in women with prior hysterectomy Main Outcome Measures: Total and hip fractures through 5 years after discontinuation Results: Hip fractures were infrequent (∼2.5 per 1,000 person years), similar between both trials and former HT and placebo groups. There was no difference in total fractures in the CEE+MPA trial for former HT vs former placebo (28.9 per 1,000 person years and 29.9 per 1,000 person years respectively) (hazard ratio [HR] 0.97; 95% CI 0.87, 1.09, p=0.63); however, in the CEE alone trial, total fractures were higher in former placebo users (36.9 per 1,000 person years) compared with former active group (31.1 per 1,000 person years), suggestive of a residual benefit of CEE against total fractures (HR 0.85, 95% CI 0.73, 0.98, p=0.03). CONCLUSIONS: We found no evidence for increased fracture risk, either sustained or transient, for former HT users compared with prior placebo women after stopping HT. There was residual benefit for total fractures in former HT users from the CEE-alone study.
Approved Proposal
305
Serum sex hormone levels and risk of hypertension in postmenopausal womenHylton Joffe
sex steroid hormones, postmenopausal, women, hypertension, estrogens, testosterone, SHBG, estrone sulfate, estradiol, DHEASObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms305p.pdf
AS110
Approved Proposal
306
Cyclooxygenase-2 (COX-2) inhibitors and cancer:  Results from the Women’s Health InitiativeRandall Harris
Observational Study
Publication
307
Predictors of optical density of lutein and zeaxanthin in retinas of older women in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health InitiativeJulie Mares
Mares JA, LaRowe TL, Snodderly DM, Moeller SM, Gruber MJ, Klein ML, Wooten BR, Johnson EJ, Chappell RJ; CAREDS Macular Pigment Study Group and Investigators. Predictors of optical density of lutein and zeaxanthin in retinas of older women in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative.  Am J Clin Nutr. 2006 Nov;84(5):1107-22.
lutein, zeaxanthin, carotenoids, dietary intake, smoking, alcohol, body fatObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17093164https://www.whi.org/researchers/bibliography/Manuscripts/ms307.pdf
AS105
Lifestyle, diet, and physical and health predictors of xanthophyll carotenoids in the retina are poorly understood.We aimed to investigate the predictors of the density of lutein and zeaxanthin in the macula of the retina.Macular pigment optical density (MPOD) was measured by heterochromatic flicker photometry. Relations to dietary lutein and zeaxanthin and to other predictors were measured in 1698 women aged 53-86 y. The women were members of observational study cohorts of the Women's Health Initiative at Iowa City, IA, Madison, WI, or Portland, OR, and participated in the Carotenoids in Age-Related Eye Disease Study (2001-2004).MPOD at 0.5 degrees from the foveal center was 30% higher in women in the highest quintile for lutein and zeaxanthin intake [x (+/-SD): 0.40 +/- 0.21] than in women in the lowest quintile (0.31 +/- 0.21) and 20% higher after adjustment for other predictors. Dietary intake of lutein, zeaxanthin, fiber, and polyunsaturated fatty acids (% of energy) together explained 3% of the variability in MPOD. Higher waist circumference and diabetes, which are related to lower MPOD, together with study site explained an additional 5% of variation. The total explained variability increased to 12% when lutein and zexanthin concentrations obtained from the serum, which were collected 4-7 y earlier, were added to the model.MPOD is directly related to dietary intake of lutein and zeaxanthin but even more strongly to serum concentrations, which may reflect unmeasured physical and medical factors that influence the uptake, distribution, and utilization of lutein and zeaxanthin. Higher abdominal body fat and diabetes are related to lower MPOD. Unknown predictors of retinal carotenoids remain.
Publication
308
Association between dietary fat intake and age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS): an ancillary study of the Women's Health InitiativeNiyati Mehta
Parekh N, Voland RP, Moeller SM, Blodi BA, Ritenbaugh C, Chappell RJ, Wallace RB, Mares JA; for the CAREDS Research Study Group. Association between dietary fat intake and age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Arch Ophthalmol. 2009;127(11):1483-1493
Polyunsaturated fatty acids, omega-3-fatty acids, total dietary fats, saturated fats, maculopathyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19901214https://www.whi.org/researchers/bibliography/Manuscripts/ms308.pdf
AS105
To evaluate the relationships between the amount and type of dietary fat and intermediate age-related macular degeneration (AMD).Women aged 50 to 79 years with high and low lutein intake from 3 sites of the Women's Health Initiative Observational Study were recruited into the Carotenoids in Age-Related Eye Disease Study. Fat intake from 1994 through 1998 was estimated using food frequency questionnaires, and AMD was assessed photographically from 2001 through 2004.Intakes of omega-6 and omega-3 polyunsaturated fatty acids, which were highly correlated (r = 0.8), were associated with approximately 2-fold higher prevalence of intermediate AMD in high vs low quintiles. However, monounsaturated fatty acid intake was associated with lower prevalence. Age interactions were often observed. In women younger than 75 years (n = 1325), total fat and saturated fatty acid intakes were associated with increased prevalence of AMD (multivariate adjusted odds ratios [95% confidence interval] for intermediate AMD, 1.7 [1.0-2.7] for quintile 5 vs quintile 1 for total fat [P = .10 for trend] and 1.6 [0.7-3.6] for saturated fatty acids [P = .23 for trend]). The associations were reversed in older women.These results support a growing body of evidence suggesting that diets high in several types of fat may contribute to the risk of intermediate AMD and that diets high in monounsaturated fatty acids may be protective.
Approved Manuscript
313
Ecological studies using supplemental case-control dataSebastien Haneuse
Observational Study
Publication
314
Aspirin use, dose, and clinical outcomes in postmenopausal women with stable cardiovascular disease: The Women’s Health Initiative Observational StudyJeffrey Berger
Berger JS, Brown DL, Burke GL, Oberman A, Kostis JB, Langer RD, Wong ND, Wassertheil-Smoller S. Aspirin use, dose, and clinical outcomes in postmenopausal women with stable cardiovascular disease. Circ Cardiovasc Qual Outcomes. 2009 Mar;2(2):78-87. Epub 2009 Mar 5
cardiovascular disease, aspirin, inflammation, cohort studyObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/20031819https://www.whi.org/researchers/bibliography/Manuscripts/ms314.pdf
Despite compelling evidence that aspirin reduces fatal and nonfatal vascular events among the overall population in various settings, women have frequently been underrepresented and their data underreported. We sought to evaluate the relationship between aspirin use, dose (81 or 325 mg), and clinical outcomes among postmenopausal women with stable cardiovascular disease (CVD).Women with CVD (n=8928) enrolled in the Women's Health Initiative Observational Study were used for this analysis. The primary outcome was the incidence of all-cause mortality and cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Among 8928 women with stable CVD, 4101 (46%) reported taking aspirin, of whom 30% were on 81 mg and 70% were on 325 mg. At 6.5 years of follow-up, no significant association was noted for aspirin use and all-cause mortality or cardiovascular events. However, after multivariate adjustment, aspirin use was associated with a significantly lower all-cause (adjusted hazard ratio, 0.86 [0.75 to 0.99]; P=0.04) and cardiovascular-related mortality (adjusted hazard ratio, 0.75 [0.60 to 0.95]; P=0.01) compared with no aspirin. Aspirin use was associated with a lower risk of cardiovascular events (adjusted hazard ratio, 0.90 [0.78 to 1.04]; P=0.14), which did not meet statistical significance. Compared with 325 mg, use of 81 mg was not significantly different for all-cause mortality, cardiovascular events, or any individual end point.After multivariate adjustment, aspirin use was associated with significantly lower risk of all-cause mortality, specifically, cardiovascular mortality, among postmenopausal women with stable CVD. No significant difference was noted between 81 mg and 325 mg of aspirin. Overall, aspirin use was low in this cohort of women with stable CVD.
Publication
316
Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian womenErnest Abel
Abel EL, Hendrix SO, McNeeley SG, Johnson KC, Rosenberg CA, Mossavar-Rahmani Y, Vitolins M, Kruger M. Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian women. Eur J Cancer Prev. 2007 Oct;16(5):446-452.
coffee, caffeine, decaffeinated, nonmelanoma skin cancerObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17923816https://www.whi.org/researchers/bibliography/Manuscripts/ms316.pdf
The purpose of this study was to assess the relationship between daily coffee consumption and nonmelanoma skin cancer. This study was a cross-sectional analysis of women enrolled in the Women's Health Initiative Observational Study (n=93 676). As nearly all cases of self-reported nonmelanoma skin cancer occurred among Caucasian women (97.8%), we focused our analyses on this group. Compared with nondrinkers, women drinking only caffeinated coffee on a daily basis had a 10.8% lower prevalence of nonmelanoma skin cancer. Consumption of six or more cups of caffeinated coffee per day was associated with a 36% reduction in nonmelanoma skin cancer. After adjusting for various demographic and life style variables, daily consumption of six or more cups was associated with a 30% reduced prevalence of nonmelanoma skin cancer. In contrast to caffeinated coffee, daily consumption of decaffeinated coffee was not associated with a significant change in self-reported nonmelanoma skin cancer for Caucasian women. Daily caffeinated coffee consumption was associated with a dose-related decreased prevalence of nonmelanoma skin cancer in Caucasian women.
Publication
317
Pelvic organ prolapse in older women: Prevalence and risk factorsIngrid Nygaard
Nygaard I, Bradley C, Brandt D, Women's Health Initiative. Pelvic organ prolapse in older women: Prevalence and risk factors. Obstet Gynecol. 2004 Sep;104(3):489-97.
prolapse, pelvic, HRTClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15339758https://www.whi.org/researchers/bibliography/Manuscripts/Ms317.pdf
AS135
We sought to estimate the prevalence of pelvic organ prolapse in older women using the Pelvic Organ Prolapse Quantification examination and to identify factors associated with prolapse.Women with a uterus enrolled at one site of the Women's Health Initiative Hormone Replacement Therapy randomized clinical trial were eligible for this ancillary cross-sectional study. Subjects underwent a Pelvic Organ Prolapse Quantification examination during a maximal Valsalva maneuver and in addition completed a questionnaire. Logistic regression was used to identify independent risk factors for each of 2 definitions of prolapse: 1) Pelvic Organ Prolapse Quantification stage II or greater and 2) the leading edge of prolapse measured at the hymen or below.In 270 participants, age (mean +/- SD) was 68.3 +/- 5.6 years, body mass index was 30.4 +/- 6.2 kg/m(2), and vaginal parity (median [range]) was 3 (0-12). The proportions of Pelvic Organ Prolapse Quantification stages (95% confidence intervals [CIs]) were stage 0, 2.3% (95% CI 0.8-4.8%); stage I, 33.0% (95% CI 27.4-39.0%); stage II, 62.9% (95% CI 56.8-68.7%); and stage III, 1.9% (95% CI 0.6-4.3%). In 25.2% (95% CI 20.1-30.8%), the leading edge of prolapse was at the hymen or below. Hormone therapy was not associated with prolapse (P =.9). On multivariable analysis, less education (odds ratio [OR] 2.16, 95% CI 1.10-4.24) and higher vaginal parity (OR 1.61, 95% CI 1.03-2.50) were associated with prolapse when defined as stage II or greater. For prolapse defined by the leading edge at or below the hymen, older age had a decreased risk (OR 0.50, 95% CI 0.27-0.92) and less education, and larger babies had an increased risk (OR 2.38, 95% CI 1.31-4.32 and OR 1.97, 95% CI 1.07-3.64, respectively).Some degree of prolapse is nearly ubiquitous in older women, which should be considered in the development of clinically relevant definitions of prolapse. Risk factors for prolapse differed depending on the definition of prolapse used.
Publication
318
Depressive symptoms, bone loss, and fractures in postmenopausal womenLeslie Spangler
Spangler L, Scholes D, Brunner RL, Robbins J, Reed SD, Newton KM, Melville JL, Lacroix AZ. Depressive symptoms, bone loss, and fractures in postmenopausal women. J Gen Intern Med. 2008 May;23(5):567-74. Epub 2008 Feb 20.
depression; bone mineral density; osteoporosis, postmenopausal; fractures; cohort studiesObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18286345https://www.whi.org/researchers/bibliography/Manuscripts/ms318.pdf
Osteoporosis and depression may be associated through common physiologic systems or risk factors.To assess the associations between depressive symptoms (Burnam's scale) or antidepressant use and bone outcomes.Prospective cohort study.A total of 93,676 postmenopausal women (50 to 79 years old) enrolled in the Women's Health Initiative Observational Study.Self-reported fractures (n = 14,982) (hip [adjudicated], spine, wrist, and "other"). Analyses included 82,410 women with complete information followed on average for 7.4 years. Bone mineral density (BMD) of the hip (n = 4539), spine (n = 4417), and whole body (n = 4502) was measured at baseline and 3 years in women enrolled at 3 densitometry study sites.Overall, there were no statistically significant associations between depressive symptoms or antidepressant therapy and 3-year change in BMD. In a subset of women not using antidepressants, there was a significant difference in whole-body BMD change between women with and without depressive symptoms (P = .05). Depressive symptoms (hazard ratio [HR] 1.08; 95% CI = 1.02 to 1.14) and antidepressant therapy (HR = 1.22; CI = 1.15 to 1.30) independently increased risk of any fracture, the majority of which occurred at "other" anatomic sites. Antidepressant therapy increased the risk of spine fracture (HR = 1.36; CI = 1.14 to 1.63). No associations were observed between depressive symptoms or antidepressant therapy and hip or wrist fracture.In this study of postmenopausal women, average age 64, we observed minimal association between depressive symptoms and 3-year changes in either BMD or fracture risk. Antidepressant use was not associated with changes in BMD, but was associated with increased risk of fractures at the spine and "other " anatomic sites.
Publication
319
The relationship between religion and cardiovascular outcomes and all-cause mortality in the Women's Health Initiative Observational StudyEliezer Schnall
Schnall E, Wassertheil-Smoller S, Swencionis C, Zemon V, Tinker L, O'Sullivan MJ, Van Horn L, Goodwin M. The relationship between religion and cardiovascular outcomes and all-cause mortality in the Women's Health Initiative Observational Study. Psychol Health. 2010 Feb;25(2):249-63. Epub 2008 Nov 17.
CVD, religionObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/20391218https://www.whi.org/researchers/bibliography/Manuscripts/ms319.pdf
Some studies suggest that religiosity may be related to health outcomes. The current investigation, involving 92,395 Women's Health Initiative Observational Study participants, examined the prospective association of religious affiliation, religious service attendance, and strength and comfort from religion with subsequent cardiovascular outcomes and death. Baseline characteristics and responses to religiosity questions were collected at enrollment. Women were followed for an average of 7.7 years and outcomes were judged by physician adjudicators. Cox proportional regression models were run to obtain hazard ratios (HR) of religiosity variables and coronary heart disease (CHD) and death. After controlling for demographic, socioeconomic, and prior health variables, self-report of religious affiliation, frequent religious service attendance, and religious strength and comfort were associated with reduced risk of all-cause mortality [HR for religious affiliation = 0.84; 95% confidence interval (CI): 0.75-0.93] [HR for service attendance = 0.80; CI: 0.73-0.87] [HR for strength and comfort = 0.89; CI: 0.82-0.98]. However, these religion-related variables were not associated with reduced risk of CHD morbidity and mortality. In fact, self-report of religiosity was associated with increased risk of this outcome in some models. In conclusion, although self-report measures of religiosity were not associated with reduced risk of CHD morbidity and mortality, these measures were associated with reduced risk of all-cause mortality.
Publication
322
Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopauseJacques Rossouw
Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, Ko M, LaCroix AZ, Margolis KL, Stefanick ML. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007 Apr 4;297(13):1465-77.
menopause, CHD , atherosclerosis , women ,sex steroid hormones, HRT, CVDClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17405972https://www.whi.org/researchers/bibliography/Manuscripts/ms322.pdf
The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998.Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials.In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [corrected] cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years; for women 10 to 19 years since menopause began, 4 per 10,000 person-years; and for women 20 or more years from menopause onset, 17 per 10,000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was -2 per 10,000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and -1 per 10,000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10,000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06).Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms.clinicaltrials.gov Identifier: NCT00000611.
Publication
323
Vaginal wall descensus and pelvic floor symptoms in older womenIngrid Nygaard
Bradley CS, Nygaard IE. Vaginal wall descensus and pelvic floor symptoms in older women. Obstet Gynecol. 2005 Oct;106(4):759-66.
pelvic organ prolapse, uterine prolapse, pelvic floor disorder, urinary incontinence, defecation disorder, voiding dysfunctionObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16199633https://www.whi.org/researchers/bibliography/Manuscripts/ms323.pdf
AS135
To understand the clinical significance of early pelvic organ prolapse in older women, we studied associations between vaginal descensus and pelvic floor symptoms.In this cross-sectional study, 270 women enrolled at one site of the Women's Health Initiative clinical trial completed a questionnaire modified from the Pelvic Floor Distress Inventory on pelvic floor symptoms and underwent a Pelvic Organ Prolapse Quantification (POP-Q) examination. We tested associations between symptoms (individual and grouped) with anterior, posterior, uterine, and maximum vaginal descensus.Mean age was 68 years. Ninety-six percent had POP-Q stages I or II. Only obstructive urinary symptoms and feeling a bulge were associated with vaginal descensus. Obstructive urinary symptom scores increased as anterior (P = .04), posterior (P < .01), and maximal (P = .01) vaginal descensus increased. Urinary incontinence or bowel symptoms were not associated with descensus of any vaginal compartment. ''See or feel a bulge,'' reported by 11 women (4%), was associated with descensus in all compartments (P < or = .04 for all) and with prolapse at or beyond the hymen (P < .001). This symptom was specific (100%), but not sensitive (16%) for prolapse, defined as descensus at or beyond the hymen.Vaginal support defects in older women are associated with obstructive urinary symptoms and the symptom of seeing or feeling a bulge. However, symptoms are not useful in discriminating between women with and without milder vaginal wall descensus. Based on these results, we suggest that other etiologies for bothersome bladder or bowel complaints be considered before performing surgery for early pelvic organ prolapse.
Publication
324
Mortality and cardiac and vascular outcomes in extremely obese womenKathleen McTigue
McTigue K, Larson JC, Valoski A, Burke G, Kotchen J, Lewis CE, Stefanick ML, Van Horn L, Kuller L. Mortality and cardiac and vascular outcomes in extremely obese women. JAMA. 2006 Jul 5;296(1):79-86
Extreme obesity, Stage III obesity, Excess weight, Mortality, Morbidity, women’s HealthObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16820550https://www.whi.org/researchers/bibliography/Manuscripts/Ms324.pdf
Obesity, typically measured as body mass index of 30 or higher, has 3 subclasses: obesity 1 (30-34.9); obesity 2 (35-39.9); and extreme obesity (> or =40). Extreme obesity is increasing particularly rapidly in the United States, yet its health risks are not well characterized.To determine how cardiovascular and mortality risks differ across clinical weight categories in women, with a focus on extreme obesity.We examined incident mortality and cardiovascular outcomes by weight status in 90,185 women recruited from 40 US centers for the Women's Health Initiative Observational Study and followed up for an average of 7.0 years (October 1, 1993 to August 31, 2004).Incidence of mortality, coronary heart disease, diabetes, and hypertension.Extreme obesity prevalence differed with race/ethnicity, from 1% among Asian and Pacific Islanders to 10% among black women. All-cause mortality rates per 10,000 person-years were 68.39 (95% confidence interval [CI], 65.26-71.68) for normal body mass index, 71.16 (95% CI, 67.68-74.82) for overweight, 84.47 (95% CI, 78.90-90.42) for obesity 1, 102.85 (95% CI, 92.90-113.86) for obesity 2, and 116.85 (95% CI, 103.36-132.11) for extreme obesity. Analyses adjusted for age, smoking, educational achievement, US region, and physical activity levels showed that weight-related risk for all-cause mortality, coronary heart disease mortality, and coronary heart disease incidence did not differ by race/ethnicity. Adjusted analyses among white and black participants showed positive trends in all-cause mortality and coronary heart disease incidence with increasing weight category. Much of the obesity-related mortality and coronary heart disease risk was mediated by diabetes, hypertension, and hyperlipidemia. In white women, weight-related all-cause mortality risk was modified by age, with obesity conferring less risk among older women.Considering obesity as a body mass index of 30 or higher may lead to misinterpretation of individual and population risks. Escalating extreme obesity may exacerbate health effects and costs of the obesity epidemic.
Publication
325
Association between alcohol intake and domain-specific cognitive function in older womenMark Espeland
Espeland MA, Coker LH, Wallace R, Rapp SR, Resnick SM, Limacher M, Powell LH, Messina CR; Women's Health Initiative Study of Cognitive Aging. Association between alcohol intake and domain-specific cognitive function in older women. Neuroepidemiology. 2006;27(1):1-12. Epub 2006 May 24.
Alcohol intake; Cognition; AgingClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16717476https://www.whi.org/researchers/bibliography/Manuscripts/ms325.pdf
AS103
Moderate levels of alcohol intake may be associated with better cognitive function; however, this relationship may vary between cognitive domains. Women, aged 65-80 years, enrolled in the Women's Health Initiative (WHI) randomized clinical trials of hormone therapy, underwent annual standardized testing for global cognitive function through the ancillary WHI Memory Study (average follow-up of 4.5 years) and domain-specific cognitive function through the WHI Study of Cognitive Aging (average follow-up of 1.7 years). Compared to nondrinkers, women reporting moderate levels of alcohol intake (<or=3 drinks per day) performed better on a measure of global cognitive function. Women reporting any alcohol intake also performed better on tests of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, and motor speed (all p < 0.05), but not spatial ability (p = 0.36). After covariate adjustment, mean scores were higher among women reporting >or=1 drink/day by 5.7% for verbal knowledge (p < 0.001) and by 5.7% for phonemic fluency (p = 0.004), compared to never-drinkers. Moderate levels of alcohol intake are associated with somewhat better cognition, which may be expressed most strongly in functions related to verbal knowledge and phonemic fluency. However, our observational study cannot rule out confounding associations with unmeasured factors.
Publication
326
The association between osteoporosis and alveolar crestal height in postmenopausal womenJean Wactawski-Wende
Wactawski-Wende J, Hausmann E, Hovey K, Trevisan M, Grossi S, Genco RJ. The association between osteoporosis and alveolar crestal height in postmenopausal women. J Periodontol. 2005 Nov;76(11 Suppl):2116-24.
Periodontal diseases; osteoporosis; bone mineral density; alveolar crestal height; postmenopause; womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16277584https://www.whi.org/researchers/bibliography/Manuscripts/ms326.pdf
AS98
Evidence supporting an association between osteoporosis and loss of alveolar crestal bone is limited. This study investigated that association in a large cohort of postmenopausal women.A cohort of 1,341 postmenopausal women aged 53 to 85 were assessed for alveolar crestal height (ACH) and bone density. ACH was determined from oral radiographs with subjects dichotomized by disease severity. Bone density was assessed by dual energy x-ray absorptiometry, with severity determined by worst T score measured (normal >-1.00; low -1.00 to -2.00; moderate -2.01 to -2.49; osteoporotic <-2.5).Compared to subjects in the normal T-score group, the odds of worse ACH increased by 39%, 59%, and 230% for those in the low, moderate, and osteoporotic groups, respectively. Adjustment for weight, education, hormone use, calcium or vitamin D supplementation, and smoking did not appreciably change the findings. Further adjustment for age attenuated the association, with osteoporotic subjects having a 1.9-fold increase of being in the worst ACH group (95% confidence interval [CI] 1.19 to 3.05). After age stratification, in women younger than 70 there was a significant trend by decreasing T-score category (P <0.02). Osteoporotic subjects had worse ACH (odds ratio [OR] = 1.95; 95% CI 1.20 to 3.17). In women aged 70 and older, worse ACH was 2.5- to 4.6-fold increased for decreasing T-score category. After adjustment, the OR (95% CI) for the low, moderate, and osteoporotic groups were 2.66 (1.12 to 6.29), 2.31 (0.89 to 6.01), and 3.57 (1.42 to 8.97), respectively (P trend = 0.026).This study found a strong and consistent association between T score and ACH in postmenopausal women. Increasing age is an important modifier of that association.
Publication
327
Low-fat dietary pattern and weight change over 7 years: The Women's Health Initiative Dietary Modification TrialBarbara Howard
Howard BV, Manson JE, Stefanick ML, Beresford SA, Frank G, Jones B, Rodabough RJ, Snetselaar L, Thomson C, Tinker L, Vitolins M, Prentice R. Low-fat dietary pattern and weight change over 7 years: The Women's Health Initiative Dietary Modification Trial. JAMA. 2006 Jan 4;295(1):39-49
low fat, high carbohydrate, dietClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16391215https://www.whi.org/researchers/bibliography/Manuscripts/Ms327.pdf
Obesity in the United States has increased dramatically during the past several decades. There is debate about optimum calorie balance for prevention of weight gain, and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed, in part, to low-fat, high-carbohydrate diets.To report data on body weight in a long-term, low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components.Randomized intervention trial of 48,835 postmenopausal women in the United States who were of diverse backgrounds and ethnicities and participated in the Women's Health Initiative Dietary Modification Trial; 40% (19,541) were randomized to the intervention and 60% (29,294) to a control group. Study enrollment was between 1993 and 1998, and this analysis includes a mean follow-up of 7.5 years (through August 31, 2004).The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable, fruit, and grain consumption and did not include weight loss or caloric restriction goals. The control group received diet-related education materials.Change in body weight from baseline to follow-up.Women in the intervention group lost weight in the first year (mean of 2.2 kg, P<.001) and maintained lower weight than control women during an average 7.5 years of follow-up (difference, 1.9 kg, P<.001 at 1 year and 0.4 kg, P = .01 at 7.5 years). No tendency toward weight gain was observed in intervention group women overall or when stratified by age, ethnicity, or body mass index. Weight loss was greatest among women in either group who decreased their percentage of energy from fat. A similar but lesser trend was observed with increases in vegetable and fruit servings, and a nonsignificant trend toward weight loss occurred with increasing intake of fiber.A low-fat eating pattern does not result in weight gain in postmenopausal women. Clinical Trial Registration ClinicalTrials.gov, NCT00000611.
Publication
328
Prospective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal womenKaren Margolis
Margolis KL, Rodabough RJ, Thomson CA, Lopez AM, McTiernan A; for the Women's Health Initiative Research Group. Prospective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal women. Arch Intern Med. 2007 Sep 24;167(17):1837-44.
Leukocyte count, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, bladder cancer, kidney cancer, lung cancer, non-Hodgkins lymphoma, cutaneous melanomaObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17893304https://www.whi.org/researchers/bibliography/Manuscripts/ms328.pdf
The immune system and inflammation are implicated in the pathogenesis of cancer. Prospective studies linking biomarkers of inflammation with cancer incidence and mortality have been inconclusive.To determine whether there is an independent association of white blood cell (WBC) count with incident cancer in postmenopausal women, a prospective cohort study was performed at 40 US clinical centers involving 143,748 postmenopausal women aged 50 to 79 years who were free of cancer at baseline and were enrolled in the Women's Health Initiative. The main outcome measures were incident invasive breast, colorectal, endometrial, and lung cancer.In multivariate models, there was a graded association of WBC count with incidence of all 4 types of cancer. Compared with the lowest quartile of WBC count (2.50-4.79x10(9) cells/L), women with a WBC count in the upper quartile (6.80-15.00x10(9) cells/L) had a statistically significantly higher risk of invasive breast cancer (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.04-1.26), colorectal cancer (HR, 1.19; 95% CI, 1.00-1.41), endometrial cancer (HR, 1.42; 95% CI, 1.12-1.79), and lung cancer (HR, 1.63; 95% CI, 1.35-1.97). The findings were similar when cancers that occurred during the first 2 years of follow-up were excluded. Statistically significant associations remained for invasive breast cancer and endometrial cancer when the analyses were limited to nonsmokers. The WBC count was also statistically significantly associated with breast cancer, lung cancer, and overall cancer mortality.Postmenopausal women with higher WBC counts have a higher risk of incident invasive breast, colorectal, endometrial, and lung cancer, as well as a higher risk of breast, lung, and overall cancer mortality.
Publication
330
Effects of estrogen with and without progestin and obesity on symptomatic gastroesophageal refluxZongli Zheng
Zheng Z, Margolis KL, Liu S, Tinker LF, Ye W; Women's Health Initiative Investigators. Effects of estrogen with and without progestin and obesity on symptomatic gastroesophageal reflux. Gastroenterology. 2008 Jul;135(1):72-81. Epub 2008 Mar 25.
estrogen, progesterone, obesity, gastroesophageal reflux diseaseClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18502208https://www.whi.org/researchers/bibliography/Manuscripts/ms330.pdf
An association between female hormones and symptomatic gastroesophageal reflux disease (GERD) and may be modified by obesity is suggested but not proven. Factors affecting GERD progression, however, are largely unknown.At 40 US clinical centers, postmenopausal women with hysterectomy (n = 10,739) were randomly assigned to receive 0.625 mg/d of conjugated equine estrogens or placebo. Women without hysterectomy (n = 16,608) were randomly assigned to receive estrogen plus progestin, given as 0.625 mg conjugated equine estrogens/d plus 2.5 mg medroxyprogesterone acetate/d, or placebo. We performed secondary analyses using data from these trials.After 1 year, there was a trend toward a higher incidence of symptomatic GER among women randomly assigned to the estrogen treatment (4.2%) than with placebo (3.1%). The estrogen plus progestin treatment did not affect this risk. Neither treatment affected the progression of existing GER symptom. There was a dose-response association between baseline obesity, particularly as measured by waist circumference, with more than double the risk of incident symptomatic GER at 1 year among women with the largest waist circumference (>or=114 cm) compared with a normal waist circumference (70-80 cm). Weight gain at 1 year was associated with elevated risk of incident symptomatic GER. Weight loss at 1 year alleviated existing GER symptoms. No interaction between hormone therapy and obesity on symptomatic GER was observed.Estrogen treatment alone, but not with progestin, may cause GER symptoms in postmenopausal women. Increasing weight and girth increases the risk of developing GER symptoms, whereas weight loss alleviates existing GER symptoms. This trial was registered at www.clinicaltrials.gov as NCT00000611.
Publication
331
Pelvic floor symptoms and lifestyle factors in older womenCatherine Bradley
Bradley CS, Kennedy CM, Nygaard IE. Pelvic floor symptoms and lifestyle factors in older women. J Womens Health (Larchmt). 2005 Mar;14(2):128-36.
irritative and obstructive urinary and bowel symptoms, urinary incontinence, pelvic floor symptomsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/15775730https://www.whi.org/researchers/bibliography/Manuscripts/ms331.pdf
AS135
To measure the prevalence of pelvic floor symptoms in noncare-seeking older women and the association between symptoms and lifestyle factors.Women enrolled at one site of the Women's Health Initiative Hormone Therapy clinical trial completed a questionnaire, modified from the Pelvic Floor Distress Inventory, on bladder, bowel, and prolapse symptoms. Individual symptoms and symptom groups were examined in a cross-sectional analysis.In the 297 women who participated, mean age was 68.2 years, mean body mass index (BMI) was 30.2 kg/m(2), and median vaginal parity was 3. The median number of symptoms endorsed was 3 (range 0-18). The most prevalent symptoms were stress urinary incontinence (51.2%), urge urinary incontinence (49.2%), urinary frequency (29.0%), straining for bowel movements (25.0%), a sense of incomplete bowel movements (34.8%), and involuntary loss of gas (33.0%). The symptom groups most frequently endorsed were stress urinary incontinence, overactive bladder, obstructive voiding, and obstructive colorectal groups (>/=1 symptom per group in 51.2%, 61.3%, 40.8%, and 48.3%, respectively). In analyses adjusted for age, BMI, caffeine ingesting, smoking, and exercise, older women more frequently reported incomplete bladder emptying (adjusted OR 3.4, 95% CI 1.3, 9.2), weak urinary stream (adjusted OR 6.4, 95% CI 2.0, 20.0), intermittent urinary stream (adjusted OR 4.0, 95% CI 1.6, 10.4), and a feeling of incomplete bowel movements (adjusted OR 2.7, 95% CI 1.2, 5.9). Women who exercised weekly had less fecal urgency (adjusted OR 0.3, 95% CI 0.2, 0.8). Coffee drinking was associated with difficulty emptying the bladder (adjusted OR 8.6, 95% CI 1.4, 55.0) and weak stream (adjusted OR 5.3, 95% CI 1.5, 19.0).Pelvic floor symptoms, especially urinary incontinence and irritative and obstructive urinary and bowel symptoms, are common in older women. Some symptoms are associated with potentially modifiable lifestyle factors.
Publication
332
Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory StudyMark Espeland
Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, Hsia J, Margolis KL, Hogan PE, Wallace R, Dailey M, Freeman R, Hays J. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004 Jun 23;291(24):2959-68.
women’s Health Initiative (WHI), cognitive function, hormone therapy, estrogen, postmenopausal women, randomized clinical trialMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15213207https://www.whi.org/researchers/bibliography/Manuscripts/Ms332.pdf
AS39
The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population.To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA).A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004.Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421).Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE).During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P =.006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P<.01). For women assigned to CEE compared with placebo, the relative risk of having a 10-unit decrease in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07).For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.
Publication
334
Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women’s Health InitiativeMargery Gass
Gass M, Cochrane BB, Larson JC, Manson, JE, Barnabei VM, Brzyski RG, Lane DS, LaValleur J, Ockene JK, Mouton CP, Barad DH. Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women’s Health Initiative. Menopause. 2011 Nov;18(11):1160-71. doi: 10.1097/gme.0b013e3182227ebd. Epub 2011 Oct 1.
sexual function, estrogen-progestin therapy, hormone therapy discontinuation, menopause, genital atrophyClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/21983008https://www.whi.org/researchers/bibliography/Manuscripts/ms334.pdf
The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI).Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6. The associations with demographic and health characteristics were determined.Sexual activity at baseline was 60.7%, 44.9%, and 28.2% in the 50- to 59-, 60- to 69-, and 70- to 79-year-old age groups, respectively. Most of the participants were satisfied with their current sexual activity (63.2%). Of those dissatisfied, 57% preferred more sexual activity. Vaginal atrophy correlated with sexual inactivity at baseline (P < 0.001). The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health, lack of satisfaction with quality of life, depression, and loss of partner (P < 0.001). The strongest predictor of sexual activity at year 1 was sexual activity at baseline (odds ratio, 96.71; 95% CI, 81.90-114.20). A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity (P = 0.01).Most women in the WHI HT Trials were satisfied with their sexual activity. Of those who were dissatisfied, the majority preferred more, rather than less, sexual activity. Vaginal atrophy at baseline correlated with sexual inactivity, and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1. HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis. This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction.
Publication
336
Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory StudySally Shumaker
Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, Masaki K, Coker LH. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA. 2004 Jun 23;291(24):2947-58.
estrogen, progesterone, dementia, cognition, incidenceMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/15213206https://www.whi.org/researchers/bibliography/Manuscripts/ms336.pdf
AS39
The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA).To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women.Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers.In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos.Probable dementia and MCI.In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04).Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.
Publication
337
Estrogen plus progestin therapy and breast cancer in recently postmenopausal womenRoss Prentice
Prentice RL, Chlebowski RT, Stefanick ML, Manson JE, Pettinger M, Hendrix SL, Hubbell FA, Kooperberg C, Kuller LH, Lane DS, McTiernan A, O'Sullivan MJ, Rossouw JE, Anderson GL. Estrogen plus progestin therapy and breast cancer in recently postmenopausal women. Am J Epidemiol. 2008 May 15;167(10):1207-16. Epub 2008 Mar 27
joint analyses, CT, OS, HT, breast cancer, colorectal cancer, ovarian cancer, endometrial cancerBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18372396https://www.whi.org/researchers/bibliography/Manuscripts/ms337.pdf
The Women's Health Initiative trial found a modestly increased risk of invasive breast cancer with daily 0.625-mg conjugated equine estrogens plus 2.5-mg medroxyprogesterone acetate, with most evidence among women who had previously received postmenopausal hormone therapy. In comparison, observational studies mostly report a larger risk increase. To explain these patterns, the authors examined the effects of this regimen in relation to both prior hormone therapy and time from menopause to first use of postmenopausal hormone therapy ("gap time") in the Women's Health Initiative trial and in a corresponding subset of the Women's Health Initiative observational study. Postmenopausal women with a uterus enrolled at 40 US clinical centers during 1993-1998. The authors found that hazard ratios agreed between the two cohorts at a specified gap time and time from hormone therapy initiation. Combined trial and observational study data support an adverse effect on breast cancer risk. Women who initiate use soon after menopause, and continue for many years, appear to be at particularly high risk. For example, for a woman who starts soon after menopause and adheres to this regimen, estimated hazard ratios are 1.64 (95% confidence interval: 1.00, 2.68) over a 5-year period of use and 2.19 (95% confidence interval: 1.56, 3.08) over a 10-year period of use.
Publication
339
Validity of diabetes self-reports in the Women's Health Initiative: comparison with medication inventories and fasting glucose measurementsKaren Margolis
Margolis KL, Lihong Qi , Brzyski R, Bonds DE, Howard BV, Kempainen S, Simin Liu , Robinson JG, Safford MM, Tinker LT, Phillips LS. Validity of diabetes self-reports in the Women's Health Initiative: comparison with medication inventories and fasting glucose measurements. Clin Trials. 2008;5(3):240-7
diabetes mellitus, validity, self-reportBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18559413https://www.whi.org/researchers/bibliography/Manuscripts/ms339.pdf
Although diabetes is conveniently assessed by self-report, few validation studies have been performed. Therefore, we studied whether self-report of prevalent and incident diabetes in Women's Health Initiative (WHI) participants was concordant with other diagnostic evidence of diabetes.A total of 161 808 postmenopausal women aged 50-79 were enrolled at 40 clinical centers in the U.S. in 1993-1998 and followed prospectively. At baseline, prevalent medication treated diabetes was defined as a self-report of physician diagnosis and treatment with insulin or oral antidiabetic drugs. During followup, incident treated diabetes was defined as a self-report of a new physician diagnosis of diabetes treated with insulin or oral drugs. Diabetes self-reports were compared with medication inventories and fasting glucose levels at baseline and during follow-up.At baseline, self-reported treated diabetes was concordant with the medication inventory in 79% of clinical trial, and 77% of observational study participants. Self-reported incident treated diabetes was concordant with the medication inventory in 78% between baseline and Year 1 in the clinical trials, in 62% between Year 1 and Year 3 in the clinical trials, and in 72% between baseline and Year 3 in the observational study. Over similar periods, 99.9% of those who did not report treated diabetes had no oral antidiabetic drugs or insulin in the medication inventory. At baseline, about 3% not reporting diabetes had fasting glucose >126 mg/dl, and 88% of these subjects subsequently reported treated diabetes during 6.9 years of follow-up.Incident self-reported diabetes treated by lifestyle alone was not determined in WHI. Medication inventories may have been incomplete and fasting glucose may have been lowered by treatment; therefore, concordance with self-reported treatment or fasting glucose > or = 126 may have been underestimated.In the WHI, self-reported prevalent and incident diabetes was consistent with medication inventories, and a high proportion of those with undiagnosed diabetes subsequently reported diabetes treatment. Self-reports of ;treated diabetes' are sufficiently accurate to allow use in epidemiologic studies.
Publication
340
Hormone therapy improves femur geometry among ethnically diverse postmenopausal participants in the Women's Health Initiative Hormone Intervention TrialsZhao Chen
Chen Z, Beck T, Cauley JA, Lewis CE, Lacroix A, Bassford T, Wu G, Sherrill D, Going S. Hormone therapy improves femur geometry among ethnically diverse postmenopausal participants in the Women's Health Initiative Hormone Intervention Trials. J Bone Miner Res. 2008 Dec;23(12):1935-45. Epub 2008 Jul 29.
fracture risk, bone density, ethnic variations, HRT, postmenopausal womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18665788https://www.whi.org/researchers/bibliography/Manuscripts/ms340.pdf
AS153
Loss of bone strength underlies osteoporotic fragility fractures. We hypothesized that hormone interventions significantly improve the structural geometry of proximal femur cross-sections. Study participants were from the Women's Health Initiative hormone intervention trials: either the conjugated equine estrogen (CEE) only (N(placebo) = 447, N(CEE) = 422) trial or the estrogen (E) plus progestin (P) (N(placebo) = 441, N(E+P) = 503) trial, who were 50-79 yr old at baseline and were followed up to 6 yr. BMD scans by DXA were conducted at baseline, year 1, year 3, and year 6. Femur geometry was derived from hip DXA scans using the hip structural analysis (HSA) method. Mixed effects models with the intent-to-treat analysis approach were used. There were no significant differences in treatment effects between the E-alone and the E + P trial, so the analyses were conducted with participants combined from both trials. Treatment benefits (p < 0.05) on femur geometry were observed as early as 1 yr after the intervention. From baseline to year 6, section modulus (a measure of maximum bending stress) was preserved, and buckling ratio (an index of cortical instability under compression) was reduced by hormone interventions (p < 0.05); the differences in the percent changes from baseline to year 6 between women on hormone intervention versus women on placebo were 2.3-3.6% for section modulus and -5.3% to - 4.3% for buckling ratio. Hormone interventions led to favorable changes in femur geometry, which may help explain the reduced fracture risk observed in hormone interventions.
Publication
341
Race/ethnicity, socioeconomic status, and lifetime morbidity burden in the Women’s Health Initiative: A cross-sectional analysisRachel Gold
Gold R, Michael YL, Whitlock EP, Hubbell FA, Mason ED, Rodriguez BL, Safford MM, Sarto GE. Race/ethnicity, socioeconomic status, and lifetime morbidity burden in the Women's Health Initiative: A cross-sectional analysis. J Womens Health (Larchmt). 2006 Dec;15(10):1161-73
race, socioeconomic status, ses, morbidityBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/17199457https://www.whi.org/researchers/bibliography/Manuscripts/ms341.pdf
We sought to assess the extent to which race/ethnicity and socioeconomic status (SES) are independently and jointly related to lifetime morbidity burden by comparing the impact of SES on lifetime morbidity among women of different racial/ethnic groups: white, black, Hispanic, American Indian/Alaska Native (AIAN), and Asian/Pacific Islander (API).Using baseline data from the Women's Health Initiative (WHI), a national study of 162,000 postmenopausal women, we measured lifetime morbidity burden using a modified version of the Charlson Index, and measured SES with educational attainment and household income. In multivariable simple polytomous logistic regression models, we first assessed the effect of SES on lifetime morbidity burden among women of each racial/ethnic group, then assessed the combined effect of race/ethnicity and SES.Five percent of all women in the study population had high lifetime morbidity burden. Women with high lifetime morbidity were more likely to be AIAN or black; poor; less educated; divorced, separated, or widowed; past or current smokers; obese; uninsured or publicly insured. Lower SES was associated with higher morbidity among most women. The extent to which morbidity was higher among lower SES compared to higher SES women was about the same among Hispanic women and white women, but was substantially greater among black and AIAN women compared with white women.This study demonstrates the importance of considering race/ethnicity and class together in relation to health outcomes.
Publication
342
Body mass index is not a good predictor of bone density: Results from WHI, CHS, and EPIDOSJohn Robbins
Robbins J, Schott AM, Azari R, Kronmal R. Body mass index is not a good predictor of bone density: results from WHI, CHS, and EPIDOS. J Clin Densitom. 2006 Jul-Sep;9(3):329-34
Osteoporosis, bone mineral density, body mass index, weight, height, BMD, BMIObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16931352https://www.whi.org/researchers/bibliography/Manuscripts/ms342.pdf
Body mass index (BMI) is often used to predict bone mineral density (BMD). This may be flawed. Large epidemiologic studies with BMI and BMD data were analyzed. Weight alone is a better predictor of BMD than BMI. Thus, when selecting individuals for dual-energy X-ray absorptiometry, weight should be used instead of BMI. Low body mass index (BMI) is frequently suggested as one of the factors that indicates the need for bone mineral density (BMD) screening for osteoporosis. The inclusion of the height-squared term in the denominator of this predictive factor is taken on faith or from other data, but it may not be reasonable in this case. We used data from three large epidemiologic studies to test the BMI, height, and weight as predictors of BMD: (1) the Women's Health Initiative (WHI) with 11,390 women; (2) the Cardiovascular Health Study (CHS) with 1,578 men and women; (3) and EPIDOS with 7,598 women. Dual-energy X-ray absorptiometry data on one or more BMD sites, the total hip, the femoral neck, and the lumbar spine from the three studies, as well as height and weight were examined. Correlation coefficients for BMI and weight with BMD were compared. Log transformed models were evaluated to compare the strengths of the models. The result of weight alone was a much better predictor of BMD for all sites in the three studies than BMI. Taller participants had larger BMDs than would have been predicted by BMI. In conclusion, BMIs should not be used to select individuals for BMD screening. A regression model using weight alone or weight and height is a better predictor of BMD in all three populations.
Publication
343
Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomyMarcia Stefanick
Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE, Schenken RS, Yasmeen S, Lessin L, Chlebowski RT, WHI Investigators. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA. 2006 Apr 12;295(14):1647-57
breast cancer, CEE, WHIClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16609086https://www.whi.org/researchers/bibliography/Manuscripts/Ms343.pdf
The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis.To determine the effects of CEE on breast cancers and mammographic findings.Following breast cancer risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included.A dose of 0.625 mg/d of CEE or an identical-appearing placebo.Breast cancer incidence, tumor characteristics, and mammogram findings.After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up.Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits.clinicaltrials.gov Identifier: NCT00000611.
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344
Elderly women diagnosed with nonspecific chest pain may be at increased cardiovascular riskJennifer Robinson
Robinson JG, Wallace R, Limacher M, Sato A, Cochrane B, Wassertheil-Smoller S, Ockene JK, Blanchette PL, Ko MG. Elderly women diagnosed with nonspecific chest pain may be at increased cardiovascular risk. J Womens Health (Larchmt). 2006 Dec;15(10):1151-60
nonspecific chest pain, risk predicition, cardiovascular, stroke, coronary heart disease, risk factorsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/17199456https://www.whi.org/researchers/bibliography/Manuscripts/ms344.pdf
Women are more likely than men to have nonspecific chest pain (NSCP) symptoms. The long-term outcomes in women discharged with a diagnosis of NSCP are unknown.The Women's Health Initiative Observational Study enrolled postmenopausal women aged 50-79 years. After excluding those with prior cardiovascular disease (CVD), 83,622 women were studied. NSCP cases were defined as having an initial primary hospital discharge diagnosis of NSCP (ICD-9 codes 786.50, 786.51, 786.59) without a prior diagnosis of coronary heart disease (CHD). Risks of subsequent CHD events were estimated from Cox proportional hazard ratio (HR) models stratified by clinic and adjusted for baseline age, cardiovascular risk factors, and hormone use.Over an average of 8 years of follow-up, 11% (230 of 2,092) of women with NSCP experienced a cardiovascular event compared with 9.5% (7,724 of 81,530) who did not. Compared with women without a hospitalization for NSCP during follow-up, those with NSCP had a greater than 2-fold higher risk of a subsequent hospitalization for clinically diagnosed angina (HR 2.18, 95% CI 1.66-2.86) and at least a 1.5-fold higher risk of nonfatal myocardial infarction (MI) (HR 1.59, 1.10-2.31), revascularization (HR 1.67, 1.28-2.20), and congestive heart failure (HR 1.75, 1.27-2.41). Women with NSCP who subsequently experienced a CHD event were more likely to be over age 65 or to have cardiovascular risk factors.Older women discharged with a diagnosis of NSCP may be at increased risk of CHD morbidity. Further research is needed to replicate these findings in other populations.
Publication
345
Conjugated equine estrogens and coronary heart disease: The Women's Health InitiativeJudith Hsia
Hsia J, Langer RD, Manson JE, Kuller L, Johnson KC, Hendrix SL, Pettinger M, Heckbert SR, Greep N, Crawford S, Eaton CB, Kostis JB, Caralis P, Prentice R, Women's Health Initiative Investigators. Conjugated equine estrogens and coronary heart disease: The Women's Health Initiative. Arch Intern Med. 2006 Feb 13;166(3):357-65
CEE, coronary events, myocardial infarction, coronary death, postmenopausal women, risk factors, HRTClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16476878https://www.whi.org/researchers/bibliography/Manuscripts/Ms345.pdf
W1, W6
In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection.A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses.During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97).Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.
Publication
346
Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsyRowan Chlebowski
Chlebowski RT, Anderson G, Pettinger M, Lane D, Langer RD, Gillian MA, Walsh BW, Chen C, McTiernan A; for the Women's Health Initiative Investigators. Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsy. Arch Intern Med. 2008 Feb 25;168(4):370-377
HRT, breast cancer, women, diagnosis, stageClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18299491https://www.whi.org/researchers/bibliography/Manuscripts/ms346.pdf
The effect of combined hormone therapy on breast cancer detection is not established.We examined the effect of combined hormone therapy on breast cancer detection in the Women's Health Initiative trial, which randomized 16,608 postmenopausal women to receive conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. Mammography and breast examinations were performed at baseline and annually per protocol, with breast biopsies based on clinical findings. The effects of conjugated equine estrogens plus medroxyprogesterone acetate on breast cancer detection was determined throughout 5.6 years of intervention using receiver operating characteristic analyses to evaluate mammography results.Conjugated equine estrogens plus medroxyprogesterone acetate increased the cumulative frequency of mammograms with abnormalities vs placebo (35.0% vs 23.0%; P < .001), which had less sensitivity for cancer detection and increased cumulative breast biopsy frequency (10.0% vs 6.1%; P < .001). Although breast cancers were significantly increased and were diagnosed at higher stages in the combined hormone group, biopsies in that group less frequently diagnosed cancer (14.8% vs 19.6%; P = .006). After discontinuation of combined hormone therapy, its adverse effect on mammograms modulated but remained significantly different from that of placebo for at least 12 months (P < .001).Use of conjugated equine estrogens plus medroxyprogesterone acetate for approximately 5 years resulted in more than 1 in 10 and 1 in 25 women having otherwise avoidable mammogram abnormalities and breast biopsies, respectively, and compromised the diagnostic performance of both. This adverse effect on breast cancer detection should be incorporated into risk-benefit discussions with women considering even short-term combined hormone therapy.clinicaltrials.gov Identifier: NCT00000611.
Publication
347
Effects of conjugated equine estrogen on stroke in the Women's Health InitiativeSusan Hendrix
Hendrix SL, Wassertheil-Smoller S, Johnson KC, Howard BV, Kooperberg C, Rossouw JE, Trevisan M, Aragaki A, Baird AE, Bray PF, Buring JE, Criqui MH, Herrington D, Lynch JK, Rapp SR, Torner J, WHI Investigators. Effects of conjugated equine estrogen on stroke in the Women's Health Initiative. Circulation. 2006 May 23;113(20):2425-34. Epub 2006 May 15.
HRT, women's health, stroke,  , e alone, estrogen plus progestinClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16702472https://www.whi.org/researchers/bibliography/Manuscripts/Ms347.pdf
W1, W6
The Women's Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database.The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10,739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin.CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.
Publication
348
Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: Results from the Women's Health Initiative randomized clinical trialRobert Brunner
Brunner RL, Gass M, Aragaki A, Hays J, Granek I, Woods N, Mason E, Brzyski R, Ockene J, Assaf A, LaCroix A, Matthews K, Wallace R, Women's Health Initiative Investigators. Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: Results from the Women's Health Initiative randomized clinical trial. Arch Intern Med. 2005 Sep 26;165(17):1976-86.
women’s Health Initiative, (WHI), hormone therapy, health-related quality of life, estrogen, menopause, depression, sleepClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16186467https://www.whi.org/researchers/bibliography/Manuscripts/ms348.pdf
The Women's Health Initiative (WHI) clinical trial of conjugated equine estrogens (CEEs), involving 10,739 postmenopausal women with hysterectomy, aged 50 to 79 years, was stopped early owing to lack of overall health benefit and increased risk of stroke. Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis, it is important to understand the overall impact of this therapy on health-related quality of life (HRQOL).All participants completed 6 specific measures of quality of life at baseline and 1 year, and a subsample (n = 1189) also completed the questions 3 years after randomization. Changes in scores were analyzed for treatment effect.Randomization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline (mean benefit, 0.4 points on a 20-point scale) and a statistically significant but small negative effect on social functioning (mean effect, -1.3 points on a 100-point scale). There were no significant improvements due to CEE in the areas of general health, physical functioning, pain, vitality, role functioning, mental health, depressive symptoms, cognitive function, or sexual satisfaction at year 1. A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes. Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline, CEE did not improve any of the HRQOL variables at year 1.In this trial of postmenopausal women with prior hysterectomy, oral CEE did not have a clinically meaningful effect on HRQOL.
Approved Proposal
349
Bone mineral density progression linked to time-to-fracture: Application to postmenopausal women taking hormone replacement therapyChristine Garnett
Clinical Trial
Publication
350
Venous thrombosis and conjugated equine estrogen in women without a uterusJ. David Curb
Curb JD, Prentice RL, Bray PF, Langer RD, Van Horn L, Barnabei VM, Bloch MJ, Cyr MG, Gass M, Lepine L, Rodabough RJ, Sidney S, Uwaifo GI, Rosendaal FR. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch Intern Med. 2006 Apr 10;166(7):772-80.
hormone replacement therapy; estrogen; venous thromboembolism; deep vein thrombosis; pulmonary embolism; coagulation; fibrinolysisClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16606815https://www.whi.org/researchers/bibliography/Manuscripts/ms350.pdf
W1, W6
Postmenopausal hormone therapy has been associated with a 2- to 3-fold increased risk of venous thromboembolism (VT) (including deep vein thrombosis and pulmonary embolism) in observational studies and secondary prevention clinical trials. Clinical trial data on the effects of estrogen alone on VT are limited.The Women's Health Initiative estrogen trial enrolled 10 739 women aged 50 to 79 years without a uterus. Participants were randomly assigned to receive conjugated equine estrogen (0.625 mg/d) or placebo.During a mean of 7.1 years, VT occurred in 111 women randomly assigned to receive estrogen (3.0 per 1000 person-years) and 86 randomly assigned to receive placebo (2.2 per 1000 person-years; hazard ratio, 1.32; 95% confidence interval, 0.99-1.75). Deep venous thrombosis was reported in 85 women randomly assigned to receive estrogen (2.3 per 1000 person-years) and 59 randomly assigned to receive placebo (1.5 per 1000 person-years; hazard ratio, 1.47; 95% confidence interval, 1.06-2.06). The VT risk was highest in the first 2 years. There were no significant interactions between estrogen use and age, body mass index, or most other VT risk factors. Comparison of Women's Health Initiative VT findings for estrogen and previous Women's Health Initiative findings for estrogen plus progestin showed that the hazard ratios for estrogen plus progestin were significantly higher than those for estrogen alone (P = .03), even after adjusting for VT risk factors.An early increased VT risk is associated with use of estrogen, especially within the first 2 years, but this risk increase is less than that for estrogen plus progestin.
Publication
352
Body size, weight cycling, and risk of renal cell carcinoma among postmenopausal women: The Women's Health Initiative (United States)Juhua Luo
Luo J, Margolis KL, Adami HO, Lopez AM, Lessin L, Ye W; for the Women's Health Initiative Investigators. Body size, weight cycling, and risk of renal cell carcinoma among postmenopausal women: The Women's Health Initiative (United States). Am J Epidemiol. 2007 Oct 1;166(7):752-9. Epub 2007 Jul 5.
Renal cell carcinoma, body size, BMI, weight change, weight cyclingBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/17615089https://www.whi.org/researchers/bibliography/Manuscripts/ms352.pdf
Although obesity is an established risk factor for renal cell carcinoma, the possible effect of central adiposity and long-term variation in weight has yet to be established. The authors studied 140,057 women aged 50-79 years enrolled in the Women's Health Initiative in the United States to examine the role of obesity, especially abdominal obesity, and weight cycling in relation to risk of renal cell carcinoma among postmenopausal women. Cox models were used to estimate relative risks and their corresponding 95% confidence intervals. During an average of 7.7 years of follow-up through September 12, 2005, a total of 269 incident cases of renal cell carcinoma were identified. Central adiposity, as indicated by waist-to-hip ratio, was an important risk factor for developing renal cell carcinoma (highest vs. lowest quartile: relative risk = 1.8, 95% confidence interval: 1.2, 2.5; p for trend = 0.0003). Moreover, women who had experienced weight cycling more than 10 times were at 2.6 times (95% confidence interval: 1.6, 4.2) increased risk compared with women whose weight was stable. Results add evidence that obesity, particularly central adiposity, is associated with an increased risk of renal cell carcinoma among postmenopausal women. Furthermore, they indicate that weight cycling is independently associated with further increased risk of this malignancy.
Publication
353
Conjugated equine estrogens and colorectal cancer incidence and survival: The Women’s Health Initiative Randomized Clinical TrialCheryl Ritenbaugh
Ritenbaugh C, Stanford JL, Wu L, Shikany JM, Schoen RE, Stefanick ML, Taylor V, Garland C, Frank G, Lane D, Mason E, McNeeley SG, Ascensao J, Chlebowski RT; For the Women's Health Initiative Investigators. Conjugated equine estrogens and colorectal cancer incidence and survival: The Women’s Health Initiative Randomized Clinical Trial. Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2609-2618. Epub 2008 Sep 30.
estrogen, CEE, colorectal cancer, hysterectomy, WHIClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18829444https://www.whi.org/researchers/bibliography/Manuscripts/ms353.pdf
In separate Women's Health Initiative randomized trials, combined hormone therapy with estrogen plus progestin reduced colorectal cancer incidence but estrogen alone in women with hysterectomy did not. We now analyze features of the colorectal cancers that developed and examine the survival of women following colorectal cancer diagnosis in the latter trial.10,739 postmenopausal women who were 50 to 79 years of age and had undergone hysterectomy were randomized to conjugated equine estrogens (0.625 mg/d) or matching placebo. Colorectal cancer incidence was a component of the monitoring global index of the study but was not a primary study endpoint. Colorectal cancers were verified by central medical record and pathology report review. Bowel exam frequency was not protocol defined, but information on their use was collected.After a median 7.1 years, there were 58 invasive colorectal cancers in the hormone group and 53 in the placebo group [hazard ratio, 1.12; 95% confidence interval (95% CI), 0.77-1.63]. Tumor size, stage, and grade were comparable in the two randomization groups. Bowel exam frequency was also comparable in the two groups. The cumulative mortality following colorectal cancer diagnosis among women in the conjugated equine estrogen group was 34% compared with 30% in the placebo group (hazard ratio, 1.34; 95% CI, 0.58-3.19).In contrast to the preponderance of observational studies, conjugated equine estrogens in a randomized clinical trial did not reduce colorectal cancer incidence nor improve survival after diagnosis.
Publication
354
Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: Results from the women's health initiative randomized trialRebecca Jackson
Jackson RD, Wactawski-Wende J, LaCroix AZ, Pettinger M, Yood RA, Watts NB, Robbins JA, Lewis CE, Beresford SA, Ko MG, Naughton MJ, Satterfield S, Bassford T, Women's Health Initiative Investigators. Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: Results from the Women's Health Initiative randomized trial. J Bone Miner Res. 2006 Jun;21(6):817-28.
fracture, bone mass, HT, osteoporotic fractureClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16753012https://www.whi.org/researchers/bibliography/Manuscripts/ms354.pdf
Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture.The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented.Postmenopausal women 50-79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk.CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45-0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44-0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47-0.72), and total fracture (HR, 0.71; 95% CI, 0.64-0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68-1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62-1.05; mid risk: HR, 1.09; 95% CI, 0.92-1.30; highest risk: HR, 1.04; 95% CI, 0.88-1.23; interaction, p = 0.42).CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit.
Publication
356
The cross-sectional relationship between body mass index, waist-hip ratio, and cognitive performance in postmenopausal women enrolled in the Women's Health InitiativeDiana Kerwin
Kerwin DR, Zhang Y, Kotchen JM, Espeland MA, Van Horn L, McTigue KM, Robinson JG, Powell L, Kooperberg C, Coker LH, Hoffmann R. The Cross-Sectional Relationship Between Body Mass Index, Waist-Hip Ratio, and Cognitive Performance in Postmenopausal Women Enrolled in the Women's Health Initiative. J Am Geriatr Soc. 2010 Aug;58(8):1427-32. doi: 10.1111/j.1532-5415.2010.02969.x. Epub 2010 Jul 14.
obesity, cognition, vascular risk factors, education, physical activity, hormone therapy, body mass index (BMI)Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/20646100https://www.whi.org/researchers/bibliography/Manuscripts/ms356.pdf
To determine whether body mass index (BMI) is independently associated with cognitive function in postmenopausal women and the relationship between body fat distribution as estimated by waist-hip ratio (WHR).Cross-sectional data analysis.Baseline data from the Women's Health Initiative (WHI) hormone trials.Eight thousand seven hundred forty-five postmenopausal women aged 65 to 79 free of clinical evidence of dementia who completed the baseline evaluation in the WHI hormone trials.Participants completed a Modified Mini-Mental State Examination (3MSE), health and lifestyle questionnaires, and standardized measurements of height, weight, body circumference, and blood pressure. Statistical analysis was performed of associations between 3MSE score, BMI, and WHR after controlling for known confounders.With the exception of smoking and exercise, vascular disease risk factors, including hypertension, waist measurement, heart disease, and diabetes mellitus, were significantly associated with 3MSE score and were included as covariables in subsequent analyses. BMI was inversely related to 3MSE score; for every 1-unit increase in BMI, 3MSE score decreased 0.988 points (P<.001) after adjusting for age, education, and vascular disease risk factors. BMI had the most pronounced association with poorer cognitive functioning scores in women with smaller waist measurements. In women with the highest WHR, cognitive scores increased with BMI.Higher BMI was associated with poorer cognitive function in women with smaller WHR. Higher WHR, estimating central fat mass, was associated with higher cognitive function in this cross-sectional study. Further research is needed to clarify the mechanism for this association.
Publication
357
The effect of conjugated equine oestrogen on diabetes incidence: The Women's Health Initiative randomised trialDenise Bonds
Bonds DE, Lasser N, Qi L, Brzyski R, Caan B, Heiss G, Limacher MC, Liu JH, Mason E, Oberman A, O'Sullivan MJ, Phillips LS, Prineas RJ, Tinker L. The effect of conjugated equine oestrogen on diabetes incidence: The Women's Health Initiative randomised trial. Diabetologia. 2006 Mar;49(3):459-68. Epub 2006 Jan 27.
diabetes mellitus, metabolic syndrome, estrogen, cardiovascular diseases,postmenopausalClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16440209https://www.whi.org/researchers/bibliography/Manuscripts/ms357.pdf
Recent clinical trials have found that the combination of conjugated equine oestrogen (CEO) and medroxyprogesterone has a protective effect on the incidence of type 2 diabetes. To determine the effect of CEO alone on the incidence of diabetes mellitus in postmenopausal women, we analysed the results of the Women's Health Initiative oestrogen-alone trial.The Women's Health Initiative is a randomised, double-masked trial comparing the effect of daily 0.625 mg CEO with placebo during 7.1 years of follow-up of 10,739 postmenopausal women who were aged 50-79 years and had previously had a hysterectomy. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin and lipoproteins were measured in an 8.6% random sample of study participants, at baseline and at 1, 3 and 6 years.The cumulative incidence of treated diabetes was 8.3% in the oestrogen-alone group and 9.3% in the placebo group (hazard ratio 0.88, 95% CI 0.77-1.01, p=0.072). During the first year of follow-up, a significant fall in insulin resistance (homeostasis model assessment of insulin resistance) in actively treated women compared with the control subjects (Year 1 baseline between-group difference -0.53) was seen. However, there was no difference in insulin resistance at the 3- or 6-year follow-up.Postmenopausal therapy with oestrogen alone may reduce the incidence of treated diabetes. The effect is smaller than that seen with oestrogen plus progestin. CEO should not, however, be used with the intention of preventing diabetes, as its well-described adverse effects preclude long-term use for primary prevention.
Publication
358
Conjugated equine estrogen influence on mammographic density in postmenopausal women in a substudy of the Women’s Health Initiative Randomized TrialAnne McTiernan
McTiernan A, Chlebowski RT, Martin C, Peck JD, Aragaki A, Pisano ED, Wang CY, Johnson KC, Manson JE, Wallace RB, Vitolins MZ, Heiss G. Conjugated equine estrogen influence on mammographic density in postmenopausal women in a substudy of the Women’s Health Initiative Randomized Trial. J Clin Oncol. 2009 Dec 20;27(36):6135-43. Epub 2009 Nov 9
mammography, Mammographic Density, Breast Cancer, Estrogen, Conjugated Equine Estrogens, Women’s Health, Women’s Health Initiative, Menopausal Hormone TherapyClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19901118https://www.whi.org/researchers/bibliography/Manuscripts/ms358.pdf
AS36
Increased mammographic density is associated with increased breast cancer risk and reduced sensitivity of screening mammography and is related to hormone exposure. However, the effects of conjugated equine estrogens (CEEs) alone on mammographic density in diverse racial/ethnic populations are not established. We examined the effect of CEE alone on mammographic density in a subsample of the Women's Health Initiative (WHI) clinical trial participants.In the WHI trial, women were randomly assigned to daily CEE 0.625 mg or placebo. The effect of CEE on mammographic percent density was determined over 1 and 2 years in a stratified random sample of 435 racially and ethnically diverse participants from 15 of 40 WHI clinics.Use of CEE resulted in mean increase in mammographic percent density of 1.6 percentage points (95% CI, 0.8 to 2.4) at year 1 compared with a mean decrease of 1.0 percentage point (95% CI, -1.7 to -0.4) in the placebo group (P < .001). The effect persisted for 2 years, with a mean increase of 1.7 percentage points (95% CI, 0.7 to 2.7) versus a mean decrease of 1.2 percentage points (95% CI, -1.8 to -0.5; P < .001) in the hormone and placebo groups, respectively. These effects were greater in women age 60 to 79 years (P = .03 for interaction across age).Use of CEE results in a modest but statistically significant increase in mammographic density that is sustained over at least a 2-year period. The clinical significance of the CEE effect on mammographic density remains to be determined.
Publication
359
Risk of fracture in women with type 2 diabetes: The Women's Health Initiative Observational StudyDenise Bonds
Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, Johnson KC, Margolis KL. Risk of fracture in women with type 2 diabetes: The Women's Health Initiative Observational Study. J Clin Endocrinol Metab. 2006 Sep;91(9):3404-10. Epub 2006 Jun 27.
Diabetes, hip fracture, osteoporosis, fractureObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16804043https://www.whi.org/researchers/bibliography/Manuscripts/ms359.pdf
Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes.The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density.Women with clinically diagnosed type 2 diabetes at baseline in the Women's Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined.All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured.The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controlling for multiple risk factors including frequency of falls [adjusted relative risk (RR) 1.20, 95% confidence interval (CI) 1.11-1.30]. In a subsample of women with baseline BMD scores, women with diabetes had greater hip and spine BMD. The elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot; spine/tailbone) among black women (RR 1.33, 95% CI 1.00-1.75) and women with increased baseline bone density (RR 1.26, 95% CI 0.96-1.66).Women with type 2 diabetes are at increased risk for fractures. This risk is also seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).
Publication
360
Interaction between body mass index and central adiposity and risk of incident cognitive impairment and dementia: Results from the Women's Health Initiative Memory StudyDiana Kerwin
Kerwin DR, Gaussoin SA, Chlebowski RT, Kuller LH, Vitolins M, Coker LH, Kotchen JM, Nicklas BJ, Wassertheil-Smoller S, Hoffmann RG, Espeland MA; for the Women's Health Initiative Memory Study. Interaction between body mass index and central adiposity and risk of incident cognitive impairment and dementia: Results from the Women's Health Initiative Memory Study. J Am Geriatr Soc. 2011 Jan;59(1):107-12. doi: 10.1111/j.1532-5415.2010.03219.x
dementia, obesity, Alzheimer disease, vascular risk factors, hormone useMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/21226681https://www.whi.org/researchers/bibliography/Manuscripts/Ms360.pdf
AS39
To assess the relationship between body mass index (BMI) and waist-hip ratio (WHR) and the clinical end points of cognitive impairment and probable dementia in a cohort of older women enrolled in the Women's Health Initiative Memory Study (WHIMS).Prospective, randomized clinical trial of hormone therapies with annual cognitive assessments and anthropometrics.Fourteen U.S. clinical sites of the WHIMS.Seven thousand one hundred sixty-three postmenopausal women aged 65 to 80 without dementia.Annual cognitive assessments, average follow-up of 4.4 years, including classification of incident cognitive impairment and probable dementia. Height, weight, waist, and hip measurements were assessed at baseline, and a waist-hip ratio (WHR) of 0.8 or greater was used as a marker of central adiposity.There were statistically significant interactions between BMI and WHR and incident cognitive impairment and probable dementia with and without adjustment for a panel of cognitive risk factors. Women with a WHR of 0.80 or greater with a BMI of 20.0 to 24.9 kg/m² had a greater risk of cognitive impairment and probable dementia than more-obese women or women with a WHR less than 0.80, although women with a WHR less than 0.80 and a BMI of 20.0 to 24.9 kg/m² had poorer scores on cognitive assessments.WHR affects the relationship between BMI and risk of cognitive impairment and probable dementia in older women. Underweight women (BMI < 20.0 kg/m²) with a WHR less than 0.80 had a greater risk than those with higher BMIs. In normal-weight to obese women (20.0-29.9 kg/m², central adiposity (WHR ≥ 0.80) is associated with greater risk of cognitive impairment and probable dementia than in women with higher BMI. These data suggest that central adiposity as a risk factor for cognitive impairment and probable dementia in normal-weight women.
Publication
361
Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health InitiativeDominic Cirillo
Cirillo DJ, Wallace RB, Wu L, Yood RA. Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative. Arthritis Rheum. 2006 Oct;54(10):3194-204.
osteoarthritis, arthoplasty, total hip replacement, total knee replacement, estrogen, progestin, risk factors, WHI, physical disability, functional limitationsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17009251https://www.whi.org/researchers/bibliography/Manuscripts/ms361.pdf
To determine the effect of hormone therapy on arthroplasty rates.We examined data from the Women's Health Initiative placebo-controlled, double-blind, randomized trials. Community-dwelling women ages 50-79 years were enrolled at 40 US clinics. Women with prior arthroplasty were excluded, yielding a sample size of 26,321 subjects. Women who had had hysterectomies (n = 10,272) were randomly assigned to receive 0.625 mg/day conjugated equine estrogens (n = 5,076), or placebo (n = 5,196), with a mean followup of 7.1 years. Those who had not had hysterectomies (n = 16,049) were randomly assigned to receive estrogen plus progestin (n = 8,240), given as 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate, or placebo (n = 7,809), with a mean followup of 5.6 years. Participants reported hospitalizations, and arthroplasties were identified by procedure codes. Arthroplasties due to hip fracture were censored. Cox proportional hazards regression was used to assess hazard ratios (HRs) and 95% confidence intervals (95% CIs) using intent-to-treat methods and outcome of time to first procedure.In the estrogen-alone trial, women receiving hormone therapy had significantly lower rates of any arthroplasty (HR 0.84 [95% CI 0.70-1.00], P = 0.05). However, this effect was borderline statistically significant for hip arthroplasty (HR 0.73 [95% CI 0.52-1.03], P = 0.07), and not significant for knee arthroplasty (HR 0.87 [95% CI 0.71-1.07], P = 0.19). In the estrogen-plus-progestin trial, there was no association for total arthroplasty (HR 0.99 [95% CI 0.82-1.20], P = 0.92) or for individual hip (HR 1.14 [95% CI 0.83-1.57], P = 0.41) or knee (HR 0.91 [95% CI 0.72-1.15], P = 0.41) arthroplasties.These data suggest that hormone therapy may influence joint health, but this observed decrease in risk may be limited to unopposed estrogen and may possibly be more important in hip than in knee osteoarthritis.
Publication
362
Effects of postmenopausal hormone therapy on rheumatoid arthritis: The Women's Health Initiative randomized controlled trialsBrian Walitt
Walitt B, Pettinger M, Weinstein A, Katz J, Torner J, Wasko MC, Howard BV; Women's Health Initiative Investigators. Effects of postmenopausal hormone therapy on rheumatoid arthritis: The Women's Health Initiative randomized controlled trials. Arthritis Rheum. 2008 Mar 15;59(3):302-10. Epub 2008 Feb 28.
Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hormone Replacement Therapy, Placebo Controlled, Prospective CohortClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18311749https://www.whi.org/researchers/bibliography/Manuscripts/ms362.pdf
To study the effects of postmenopausal hormone therapy (PHT) on the incidence and severity of rheumatoid arthritis (RA).The Women's Health Initiative randomized controlled trials evaluated the effects of unopposed estrogen (E-alone) and estrogen plus progestin (E+P) compared with placebo on a diverse set of health outcomes over 7.1 and 5.6 years, respectively. RA cases were identified using historical and medication data. The hazard of developing RA was estimated using Cox proportional hazards regression models. Disease symptom severity was estimated using the Short Form 36 (SF-36) and self-reported joint pain scores at baseline and after 1 year. Mean changes in severity were compared using linear regression models.Of the 27,347 participants, 63 prevalent cases and 105 incident cases of RA were identified. A nonsignificant reduction in the risk of developing RA (hazard ratio 0.74; 95% confidence interval [95% CI] 0.51, 1.10) was noted with PHT use. PHT use led to improved SF-36 scores in unadjusted analyses (percent change 12.5%; 95% CI -24.45, -0.57) but not after adjustment for relevant covariates (P = 0.33). Nonsignificant improvements in joint pain scores were seen with PHT use (odds ratio [OR] 4.10; 95% CI 0.83, 20.20). PHT did not improve swelling (OR 1.27; 95% CI 0.08, 19.63) or prevent new joint pains (OR 0.72; 95% CI 0.11, 4.68) in RA participants.There were no statistically significant differences in the risk of developing RA or the severity of RA between the PHT and placebo groups.
Publication
363
Long-term exposure to air pollution and incidence of cardiovascular events in womenJoel Kaufman
Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH, Anderson GL, Kaufman JD. Long-term exposure to air pollution and incidence of cardiovascular events in women.  N Engl J Med. 2007 Feb 1;356(5):447-58.
particulate air pollution, incident cardiovascular events, sedentary lifestyle, prior health conditionsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17267905https://www.whi.org/researchers/bibliography/Manuscripts/ms363.pdf
AS150
Fine particulate air pollution has been linked to cardiovascular disease, but previous studies have assessed only mortality and differences in exposure between cities. We examined the association of long-term exposure to particulate matter of less than 2.5 microm in aerodynamic diameter (PM2.5) with cardiovascular events.We studied 65,893 postmenopausal women without previous cardiovascular disease in 36 U.S. metropolitan areas from 1994 to 1998, with a median follow-up of 6 years. We assessed the women's exposure to air pollutants using the monitor located nearest to each woman's residence. Hazard ratios were estimated for the first cardiovascular event, adjusting for age, race or ethnic group, smoking status, educational level, household income, body-mass index, and presence or absence of diabetes, hypertension, or hypercholesterolemia.A total of 1816 women had one or more fatal or nonfatal cardiovascular events, as confirmed by a review of medical records, including death from coronary heart disease or cerebrovascular disease, coronary revascularization, myocardial infarction, and stroke. In 2000, levels of PM2.5 exposure varied from 3.4 to 28.3 microg per cubic meter (mean, 13.5). Each increase of 10 microg per cubic meter was associated with a 24% increase in the risk of a cardiovascular event (hazard ratio, 1.24; 95% confidence interval [CI], 1.09 to 1.41) and a 76% increase in the risk of death from cardiovascular disease (hazard ratio, 1.76; 95% CI, 1.25 to 2.47). For cardiovascular events, the between-city effect appeared to be smaller than the within-city effect. The risk of cerebrovascular events was also associated with increased levels of PM2.5 (hazard ratio, 1.35; 95% CI, 1.08 to 1.68).Long-term exposure to fine particulate air pollution is associated with the incidence of cardiovascular disease and death among postmenopausal women. Exposure differences within cities are associated with the risk of cardiovascular disease.
Approved Proposal
364
Hormone replacement therapy and chronic heart failure incidence and outcomes in post-menopausal womenPhillip Greenland
heart failure, incidence, outcomes, estrogen, progesterone, hormone replacementClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/Ms364pv2.pdf
AS196
Publication
367
The Women’s Health Initiative: A potential resource for future studies of autoimmune diseasesBarbara Howard
Howard BV. The Women's Health Initiative: a potential resource for future studies of autoimmune diseases. Autoimmunity. 2004 Jun;37(4):265-8.
WHI, longitudinal,Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/15518039https://www.whi.org/researchers/bibliography/Manuscripts/ms367.pdf
The women's health initiative observational and clinical trials cohort is one of the largest and most carefully characterized group of postmenopausal women who have undergone long-term follow-up. Although outcome assessment has focused on the outcomes of CVD, cancer, and fractures, a wealth of data have been collected, which could form the basis for researchers interested in autoimmune diseases to begin important studies. Baseline and follow-up blood samples and DNA samples are available upon application to the study's Design and Analysis Committee and publications can be planned based on the current dataset upon application to the Publications and Presentations Committee. In both of these cases, one of the principal investigators from the 40 clinical centers or the Central Coordinating Center would need to be involved as a collaborator. Upon obtaining appropriate IRB approval, it could be possible to recontact women to collect additional information to verify outcomes or obtain further follow-up data. In addition to the WHI, the National Institutes of Health have funded a number of other large cohort studies that could be of use for researchers of autoimmune diseases. These include several longitudinal studies of diabetes funded by the NIDDK and several other large cardiovascular cohorts funded by the National Heart, Blood and Lung institute (e.g. ARIC, CARDIA and CHS. In addition, the national Cancer Institute has funded studies of large cohorts of Whites, Blacks, Hispanics, and American Indians in the United States. In all these studies, individuals have undergone baseline assessment for environmental and lifestyle risk factors and are being followed for long-term health outcomes. Given the time and expense devoted to the Women's Health initiative and these other studies, it would be of great value if researchers interested in a wide variety of chronic diseases would make use of these rich sources of data.
Publication
368
Postmenopausal hormone therapy in relation to cardiovascular disease and cognitionRoss Prentice
Prentice RL. Postmenopausal hormone therapy in relation to cardiovascular disease and cognition. Proceedings of the 47th Study Group of the Royal College of Obstetricians and Gynecologists. 2004.
postmenopausal hormone therapy, cardiovascular disease, cognitionClinical Trial
Publication
369
A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal womenSimin Liu
Liu S, Tinker L, Song Y, Rifai N, Bonds DE, Cook NR, Heiss G, Howard BV, Hotamisligil GS, Hu FB, Kuller LH, Manson JE. A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. Arch Intern Med. 2007 Aug 13-27;167(15):1676-85.
type 2 diabetes mellitus, interleukin-6, tumor necrosis factor-α, C-reactive protein, inflammation, insulin resistanceObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17698692https://www.whi.org/researchers/bibliography/Manuscripts/ms369.pdf
AS132
Inflammatory cytokines, including tumor necrosis factor alpha, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations.Among 82,069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor alpha receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease.After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor alpha receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups.These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.
Publication
370
Benchmarks for designing two-stage studies using modified mini-mental state examinations: Experience from the Women’s Health Initiative Memory StudyMark Espeland
Espeland MA, Rapp SR, Robertson J, Granek I, Murphy C, Albert M, Bassford T. Benchmarks for designing two-stage studies using modified mini-mental state examinations: Experience from the Women's Health Initiative Memory Study. Clin Trials. 2006;3(2):99-106.
Dementia screening; CognitionClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16773952https://www.whi.org/researchers/bibliography/Manuscripts/ms370.pdf
AS39
The most efficient approach for studies examining the incidence of dementia involves a brief screening instrument to identify participants for more extensive testing to identify cognitive impairment. The modified mini-mental state examination (3MS) is commonly used as this initial screen in such two-stage designs, however its properties for this role require further study.We use data from the Women's Health Initiative Memory Study to contrast design options in two-stage designs.This trial enrolled 7251 participants with nine or more years of education who were aged 65-79 and followed an average of four to five years. Logistic regression was used to examine the case yields at varying two-stage 3MS cutpoints. The efficiency of using different examination schedules and restricting enrollment to higher risk women was examined.Probable dementia is associated with marked decline in 3MS scores. The percentages of women classified with probable dementia ranged from 7.95% (3MS 85-88) to 50.0% (3MS < 70). The numbers [95% confidence interval] of enrolled women necessary to detect one case of probable dementia (four-year follow-up) for baseline 3MS scores of 100, 95, 90 and 85 were estimated as 1477 [389, 5618], 253 [134, 481], 53 [34, 85], and 14 [9, 23], respectively. Compared to annual testing, administration every two years increased the number of required enrollees by 11%, but decreased the number of test administrations by 46%.Our findings are influenced by the characteristics of our study group, its rates of retention, and the study protocol, and may not fully generalize to other settings.The 3MS can serve as an efficient basis for two-stage study designs and a cutpoint of < or = 88 is reasonable for populations with similar characteristics. Studies may improve efficiency by using the 3MS during screening to eliminate women with low risk for dementia and by conducting testing every two years.
Publication
371
Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS): Ancillary study of the Women's Health InitiativeSuzen Moeller
Moeller SM, Parekh N, Tinker L, Ritenbaugh C, Blodi B, Wallace RB, Mares JA, CAREDS Research Study Group. Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the carotenoids in age-related eye disease study (CAREDS): Ancillary study of the Women's Health Initiative. Arch Ophthalmol. 2006 Aug;124(8):1151-62.
lutein, zeaxanthin, carotenoids, age-related maculopathy, serum, dietObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16908818https://www.whi.org/researchers/bibliography/Manuscripts/ms371.pdf
AS105
To evaluate the relationship between dietary lutein plus zeaxanthin and intermediate age-related macular degeneration (AMD).Women aged 50 to 79 years in Iowa, Wisconsin, and Oregon with intake of lutein plus zeaxanthin above the 78th (high) and below the 28th (low) percentiles at baseline in the Women's Health Initiative Observational Study were recruited 4 to 7 years later into the Carotenoids in Age-Related Eye Disease Study (CAREDS), when the presence of AMD was determined by fundus photographs. Logistic regression analyses examined the prevalence of AMD in 1787 CAREDS participants, after accounting for potential covariates.The prevalence of intermediate AMD was not statistically different between the high and low lutein plus zeaxanthin intake recruitment groups after adjusting for age (odds ratio, 0.96; 95% confidence interval, 0.75-1.23). Limiting analyses to women younger than 75 years with stable intake of lutein plus zeaxanthin, without a history of chronic diseases that are often associated with diet changes, substantially lowered odds ratios (0.57; 95% confidence interval, 0.34-0.95). Exploratory analyses of advanced AMD in 34 participants resulted in protective, but statistically nonsignificant, associations in the overall sample and in women younger than 75 years.Diets rich in lutein plus zeaxanthin may protect against intermediate AMD in healthy women younger than 75 years.
Publication
372
Factors associated with 5-year risk of hip fracture in postmenopausal womenJohn Robbins
Robbins J, Aragaki AK, Kooperberg C, Watts N, Wactawski-Wende J, Jackson RD, LeBoff MS, Lewis CE, Chen Z, Stefanick ML, Cauley J. Factors associated with 5-year risk of hip fracture in postmenopausal women. JAMA. 2007 Nov 28;298(20):2389-98.
Hip fracture, risk factors, women, observational study,Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18042916https://www.whi.org/researchers/bibliography/Manuscripts/ms372.pdf
The 329,000 hip fractures that annually occur in the United States are associated with high morbidity, mortality, and cost. Identification of those at high risk is a step toward prevention.To develop an algorithm to predict the 5-year risk of hip fracture in postmenopausal women.A total of 93,676 women who participated in the observational component of the Women's Health Initiative (WHI), a multiethnic longitudinal study, were used to develop a predictive algorithm based on commonly available clinical features. Selected factors that predicted hip fracture were then validated by 68,132 women who participated in the clinical trial. The model was tested in a subset of 10,750 women who had undergone dual-energy x-ray absorptiometry (DXA) scans for bone mass density assessment.The prediction of centrally adjudicated hip fracture, measured by the area under the receiver operator characteristic (ROC) curves.During a mean (SD) follow-up of 7.6 (1.7) years, 1132 hip fractures were identified among women participating in the observational study (annualized rate, 0.16%), whereas during a mean follow-up of 8.0 (1.7) years, 791 hip fractures occurred among women participating in the clinical trial (annualized rate, 0.14%). Eleven factors predicted hip fracture within 5 years: age, self-reported health, weight, height, race/ethnicity, self-reported physical activity, history of fracture after age 54 years, parental hip fracture, current smoking, current corticosteroid use, and treated diabetes. Receiver operating characteristic curves showed that the algorithm had an area under the curve of 80% (95% confidence interval [CI], 0.77%-0.82%) when tested in the cohort of different women who were in the clinical trial. A simplified point score was developed for the probability of hip fracture. Receiver operating characteristic curves comparing DXA-scan prediction based on a 10% subset of the cohort and the algorithm among those who participated the clinical trial were similar, with an area under the curve of 79% (95% CI, 73%-85%) vs 71% (95% CI, 66%-76%).This algorithm, based on 11 clinical factors, may be useful to predict the 5-year risk of hip fracture among postmenopausal women of various ethnic backgrounds. Further studies are needed to assess the clinical implication of the algorithm in general and specifically to identify treatment benefits.
Publication
373
Conjugated equine estrogens and peripheral arterial disease risk: The Women's Health InitiativeJudith Hsia
Hsia J, Criqui MH, Herrington DM, Manson JE, Wu L, Heckbert SR, Allison M, McDermott MM, Robinson J, Masaki K, Women's Health Initiative Research Group. Conjugated equine estrogens and peripheral arterial disease risk: The Women's Health Initiative. Am Heart J. 2006 Jul;152(1):170-6.
estrogen, CVD, postmenopausal women, peripheral arterial disease, mortalityClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16824852https://www.whi.org/researchers/bibliography/Manuscripts/ms373.pdf
Estradiol reduced progression of ultrasonographic carotid disease in a randomized trial. No trials of unopposed estrogen for prevention of lower extremity arterial disease or aortic aneurysm have been conducted.The Estrogen Alone trial randomized 10739 postmenopausal women with prior hysterectomy, mean age 63.6 +/- 7.3 years, to conjugated equine estrogens (CEE 0.625 mg/d) or placebo and documented health outcomes over an average of 7.1 +/- 1.6 years.A trend toward increased risk of peripheral arterial events with CEE was observed (hazard ratio [HR] 1.32, 95% CI 0.99-1.77). Carotid arterial events (HR 1.19, 95% CI 0.82-1.74), lower extremity arterial events (HR 1.41, 95% CI 0.86-2.32), and abdominal aortic aneurysm (HR 2.40, 95% CI 0.92-6.23) were more frequent, but not individually significant, in the CEE group. However, the composite of lower extremity arterial disease/abdominal aortic aneurysm was significantly more frequent among women assigned to CEE (HR 1.63, 95 % CI 1.05-2.51). In subgroup analyses, no clear pattern of risk with CEE was apparent by age or by time since menopause.Unopposed CEE conferred no protection against peripheral arterial disease among generally healthy postmenopausal women; in fact, there was a suggestion of increased risk.
Publication
375
Intentional weight loss and risk of lymphohematopoietic cancersAnneclaire De Roos
De Roos AJ, Ulrich CM, Ray RM, Mossavar-Rahmani Y, Rosenberg CA, Caan BJ, Thomson CA, McTiernan A, Lacroix AZ. Intentional weight loss and risk of lymphohematopoietic cancers. Cancer Causes Control. 2010 Feb;21(2):223-36. Epub 2009 Oct 23
lymphoma, leukemia, myeloma, melanoma, obesity, weight cyclingObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19851877https://www.whi.org/researchers/bibliography/Manuscripts/ms375.pdf
We hypothesized that intentional weight loss may be associated with development of lymphohematopoietic cancers, based on observations of immune suppression following weight loss in short-term studies.At the baseline of the Women's Health Initiative Observational Study (1994-1998), participants reported information about intentional weight loss episodes in the past 20 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) among 81,219 women for associations between past intentional weight loss and risk of developing non-Hodgkin lymphoma (NHL), leukemia, and multiple myeloma during an average 9.9 years of follow-up.The risk of NHL was associated with having lost a large maximum amount of weight (> or =50 pounds, HR = 1.68, 95% CI 1.13-2.50). NHL risk also varied by the frequency of intentional weight loss; women had increased risk if they lost 50 pounds or more > or =3 times (HR = 1.97, 95% CI 0.93-4.16; p trend by frequency = 0.09) or 20-49 pounds > or =3 times (HR = 1.55, 95% CI 1.00-2.40; p trend = 0.05), but there was no risk associated with smaller amounts of weight loss (10-19 pounds > or =3 times, HR = 0.78, 95% CI 0.46-1.33). These associations persisted with adjustment for body mass index at different ages. We observed non-significant associations of similar magnitude for multiple myeloma, but past intentional weight loss episodes were not associated with leukemia.Further assessment of intentional weight loss as a possible risk factor for lymphomas may provide insight into the etiology of these cancers.
Publication
376
Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of womenYiqing Song
Song Y, Manson JE, Tinker L, Rifai N, Cook NR, Hu FB, Hotamisligil GS, Ridker PM, Rodriguez BL, Margolis KL, Oberman A, Liu S. Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women. Diabetes. 2007 Jul;56(7):1898-904. Epub 2007 Mar 27.
type 2 diabetes mellitus, endothelial activation, E-selectin, intercellular adhesion molecule-1, vascular adhesion molecule-1, insulin resistanceObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17389327https://www.whi.org/researchers/bibliography/Manuscripts/ms376.pdf
AS132
Elevated circulating levels of soluble adhesion molecules as markers of endothelial dysfunction have been related to insulin resistance and its associated metabolic abnormalities. However, their associations with type 2 diabetes remain inconclusive. We conducted a prospective nested case-control study to examine the associations between plasma levels of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) and diabetes risk among 82,069 initially healthy women aged 50-79 years from the Women's Health Initiative Observational Study. During a median follow-up of 5.9 years, 1,584 incident diabetes case subjects were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood draw, and follow-up time. Baseline median levels of the biomarkers were each significantly higher among case subjects than among control subjects (E-selectin, 49 vs. 37 ng/ml; ICAM-1, 324 vs. 280 ng/ml; and VCAM-1, 765 vs. 696 ng/ml [all P values <0.001]). After adjustment for risk factors, the relative risks of diabetes among women in the highest quartile versus those in the lowest quartile were 3.46 for E-selectin (95% CI 2.56-4.68; P for trend <0.0001), 2.34 for ICAM-1 (1.75-3.13; P for trend <0.0001), and 1.48 for VCAM-1 (1.07-2.04; P for trend = 0.009). E-selectin and ICAM-1 remain significant in each ethnic group. In conclusion, higher levels of E-selectin and ICAM-1 were consistently associated with increased diabetes risk in a multiethnic cohort of U.S. postmenopausal women, implicating an etiological role of endothelial dysfunction in the pathogenesis of type 2 diabetes.
Publication
377
Another treatment gap: Restarting secondary prevention medications: The Women’s Health InitiativeJennifer Robinson
Robinson JG, Wallace R, Safford MM, Pettinger M, Cochrane B, Ko MG, O'Sullivan MJ, Masaki K, Petrovich H. Another treatment gap: Restarting secondary prevention medications: The Women’s Health Initiative. J Clin Lipidol. 2010 Feb;4(1):36-45.
medication utilization, prevention, cardiovascular, stroke, coronary heart disease, diabetes, risk factorsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/20354566https://www.whi.org/researchers/bibliography/Manuscripts/ms377.pdf
Women's long-term patterns of evidence-based preventive medication utilization following a coronary heart disease (CHD) diagnosis have not been sufficiently studied.Postmenopausal women 50-79 years were eligible for randomization in the Women's Health Initiative's (WHI) hormone trials if they met inclusion and exclusion criteria and were >80% adherent during a placebo-lead-in period and in the dietary modification trial if they were willing to follow a 20% fat diet. Those with adjudicated myocardial infarction or coronary revascularization after the baseline visit were included in the analysis (n=2627). Baseline visits occurred between 1993 and 1998, then annually until the trials ended in 2002 through 2005; medication inventories were obtained at baseline and years 1, 3, 6 and 9.Utilization at the first WHI visit following a CHD diagnosis increased over time for statins (49% to 72%; p<0.0001), beta-blockers (49% to 62%; p=0.003), and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers (ACEI/ARBs ) [26 to 43%; p<0.0001]. Aspirin use remained stable at 76% (p=0.09). Once women reported using a statin, aspirin, or beta-blocker, 84-89% reported use at 1 or more subsequent visits, with slightly lower rates for ACEI/ARBS (76%). Statin, aspirin, beta-blocker, or ACEI/ARB use was reported at 2 or more consecutive visits by 57%, 66%, 48%, and 28% respectively. These drugs were initiated or resumed at a later visit by 24%, 17%, 15%, and 17%, respectively, and were never used during the period of follow-up by 19%, 10%, 33%, and 49% respectively.Efforts to improve secondary prevention medication utilization should target both drug initiation and restarting drugs in patients who have discontinued them.
Publication
378
Expression and ambivalence over expression of negative emotion: Cross-sectional associations with psychosocial factors and health-related quality of life in postmenopausal womenYvonne Michael
Michael YL, Wisdom JP, Perrin N, Bowen D, Cochrane BB, Brzyski R, Ritenbaugh C. Expression and ambivalence over expression of negative emotion: Cross-sectional associations with psychosocial factors and health-related quality of life in postmenopausal women. J Women Aging. 2006;18(2):25-40.
Emotion, Psychosocial, Behavioral, Health-related quality of life, Psychometric, Validation, Race/ethnicityBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16782658https://www.whi.org/researchers/bibliography/Manuscripts/ms378.pdf
Inhibition of emotional expression has been associated with the incidence and progression of breast cancer and other chronic illnesses. The important health-related factor, however, may be ambivalence about the expression of emotions rather than repression itself. This cross-sectional analysis of baseline data from 159,557 participants in the Women's Health Initiative examined the influence of expression of negative emotion and ambivalence about expression of emotion on psychosocial factors and health-related quality of life measured by the Medical Outcomes Study Short-form 36 (SF-36). Overall, observed correlations were modest but in the expected direction; that is, greater ambivalence about negative emotional expression was associated with worse general health and poorer psychosocial risk profile. Ambivalence about expressing negative emotion was more highly correlated with psychosocial factors and health-related quality of life than emotional expression. In general, our analysis supports prior studies suggesting that ambivalence may be more important to consider in studies of health-related outcomes than expression.
Publication
380
Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health InitiativeMary Cushman
Cushman M, Larson JC, Rosendaal FR, Heckbert SR, Curb JD, Phillips LS, Baird AE, Eaton CB, Stafford RS. Biomarkers, menopausal hormone therapy and risk of venous thrombosis: The Women's Health Initiative. Res Pract Thromb Haemost. 2018 Apr 17;2(2):310-319. doi: 10.1002/rth2.12100. eCollection 2018 Apr
D‐dimer; blood coagulation; menopausal hormone therapy; risk assessment; risk factor; venous thromboembolism; venous thrombosisClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/30046733https://www.whi.org/researchers/bibliography/Manuscripts/Ms380.pdf
W6
Background: Oral menopausal hormone therapy causes venous thrombosis but whether biomarkers of thrombosis risk can identify women at risk is unknown. Methods: We completed a nested case control study in the two Women's Health Initiative hormone trials; 27 347 women aged 50-79 were randomized to hormone therapy (conjugated equine estrogen with or without medroxyprogesterone acetate) or placebo. With 4 years follow-up, biomarkers were measured using stored baseline samples prior to starting treatment, and one-year later, in 215 women who developed thrombosis and 867 controls. Results: Overall, lower protein C and free protein S, and higher D-dimer, prothrombin fragment 1.2 and plasmin-antiplasmin complex were associated with risk of future thrombosis with odds ratios ranging from 1.9 to 3.2. Compared to women with normal biomarkers assigned to placebo, the risk of thrombosis with hormone therapy was increased among women with abnormal biomarkers, especially elevated D-dimer, elevated plasmin-antiplasmin, and low free protein S; the largest association was for D-dimer: odds ratio 6.0 (95% CI 3.6-9.8). Differences in associations by hormone use were not significant on the multiplicative scale. Considering a multi-marker score of eight biomarkers, women with three or more abnormal biomarkers had 15.5-fold increased odds of VT (95% CI 6.8-35.1). One-year changes in biomarkers were not robustly associated with subsequent thrombosis risk. Conclusion: Abnormal levels of biomarkers of thrombosis risk identified women at increased risk of future venous thrombosis with oral menopausal hormone therapy. Findings support the potential for clinical use of D-dimer testing in advance of hormone therapy prescription.
Approved Proposal
381
Estimating ovarian cancer riskGarnet Anderson
ovarian cancer, estimation, fallopian tube cancer, primary peritoneal cancer, riskBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/Ms381p.pdf
AS282, AS97
Publication
384
Comparison of frailty phenotypes for prediction of mortality, incident falls, and hip fractures in older womenOleg Zaslavsky
Zaslavsky O, Zelber-Sagi S, Gray SL, LaCroix AZ, Brunner RL, Wallace RB, O'Sullivan MJ, Cochrane B, Woods NF. Comparison of frailty phenotypes for prediction of mortality, incident falls, and hip fractures in older women. J Am Geriatr Soc. 2016 Sep;64(9):1858-62. doi: 10.1111/jgs.14233. Epub 2016 Jun 16.
SF-36; falls; frailty; function; hip fracture; mortality; predictive abilityClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/27310179https://www.whi.org/researchers/bibliography/Manuscripts/Ms384.pdf
OBJECTIVES: To compare the ability of the commonly used Women's Health Initiative (WHI) and Cardiovascular Health Study (CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older. DESIGN: Longitudinal cohort study. SETTING: WHI Clinical Trial. PARTICIPANTS: Participants with data for WHI and CHS frailty phenotypes (N = 3,558). MEASUREMENTS: Frailty was operationally defined in the CHS as the presence of three or more of weight loss, poor energy, weakness, slowness, and low physical activity. WHI operationalized frailty similarly but with the RAND-36 physical function scale substituted for slowness and weakness (RAND-36 physical function scale score <13 = 2 points, 13-78 = 1 point, >78 = 0 points). Frailty was defined as a summary score of 3 or greater, prefrailty as a score of 2 or 1, and nonfrailty as a score of 0. Outcomes were modeled using Cox regression. Harrell C-statistics were compared for models containing alternative instruments. RESULTS: Approximately 5% of participants were frail based on the CHS or WHI phenotype. The WHI frailty phenotype was associated with higher rates of falls (hazard ratio (HR) = 1.48, P = .003), hip fracture (HR = 1.87, P = .04), and death (HR = 2.32, P < .001). Comparable HRs in CHS-phenotype frail women were 1.32 (P = .04), 1.08 (P = .83), and 1.91 (P < .001), respectively. Harrell C-statistics revealed marked but insignificant differences in predicting abilities between CHS and WHI phenotype models (P > .50 for all). CONCLUSION: The WHI phenotype, which does not require direct measurements of physical performance, might offer a practical advantage for epidemiological and clinical needs.
Publication
385
Development of a glycemic index database for food frequency questionnaires used in epidemiologic studiesMarian Neuhouser
Neuhouser ML, Tinker LF, Thomson C, Caan B, Horn LV, Snetselaar L, Parker LM, Patterson RE, Robinson-O'Brien R, Beresford SA, Shikany JM. Development of a glycemic index database for food frequency questionnaires used in epidemiologic studies. J Nutr. 2006 Jun;136(6):1604-9.
dietary assessment, glycemic index, carbohydrate, insulin, glucoseClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16702328https://www.whi.org/researchers/bibliography/Manuscripts/ms385.pdf
AS111
Consumption of foods with a high glycemic index (GI) or glycemic load (GL) is hypothesized to contribute to insulin resistance, which is associated with increased risk of diabetes mellitus, obesity, cardiovascular disease, and some cancers. However, dietary assessment of GI and GL is difficult because values are not included in standard food composition databases. Our objective was to develop a database of GI and GL values that could be integrated into an existing dietary database used for the analysis of FFQ. Food GI values were obtained from published human experimental studies or imputed from foods with a similar carbohydrate and fiber content. We then applied the values to the Women's Health Initiative (WHI) FFQ database and tested the output in a random sample of previously completed WHI FFQs. Of the 122 FFQ line items (disaggregated into 350 foods), 83% had sufficient carbohydrate (>5 g/serving) for receipt of GI and GL values. The foods on the FFQ food list with the highest GL were fried breads, potatoes, pastries, pasta, and soft drinks. The fiber content of foods had very little influence on calculated GI or GL estimates. The augmentation of this FFQ database with GI and GL values will enable etiologic investigations of GI and GL with numerous disease outcomes in the WHI and other epidemiologic studies that utilize this FFQ.
Publication
386
The role of antioxidants and vitamin A in ovarian cancer: Results from the Women’s Health InitiativeCynthia Thomson
Thomson CA, Neuhouser ML, Shikany JM, Caan BJ, Monk BJ, Mossavar-Rahmani Y, Sarto G, Parker LM, Modugno F, Anderson GL. The role of antioxidants and vitamin A in ovarian cancer: Results from the Women’s Health Initiative. Nutr Cancer. 2008;60(6):710-9.
ovarian cancer, dietary predictorsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/19005970https://www.whi.org/researchers/bibliography/Manuscripts/ms386.pdf
Antioxidant nutrients and carotenoids have been inconsistently associated with ovarian cancer risk. We examined the relationship between intake of dietary and supplemental antioxidant nutrients including vitamins C, E, and selenium as well as carotenoids and vitamin A and ovarian cancer in 133,614 postmenopausal women enrolled in the Women's Health Initiative (WHI) study. Dietary intake was assessed using a food frequency questionnaire, and ovarian cancer endpoints were centrally adjudicated. Cox regression models were used to estimate the risk for invasive ovarian cancer in relation to each of the antioxidant nutrients and carotenoids under consideration using models stratified for a WHI study component. A total of 451 cases of invasive ovarian cancer were diagnosed over 8.3 yr of follow-up. Dietary intake at baseline was not significantly different for cases vs. controls. Cases reported greater intake of supplemental vitamin C (358.0 mg/day vs. 291.6 mg/day, respectively; P = 0.024). Multivariate modeling (P for trend) of the risk for developing ovarian cancer did not suggest any significant relationships among dietary factors and ovarian cancer risk. The results from this prospective study of well-nourished, postmenopausal women suggest that intake of dietary antioxidants, carotenoids, and vitamin A are not associated with a reduction in ovarian cancer risk.
Publication
387
Major and minor ECG abnormalities in asymptomatic women and risk of cardiovascular events and mortalityPablo Denes
Denes P, Larson JC, Lloyd-Jones DM, Prineas RJ, Greenland P. Major and minor ECG abnormalities in asymptomatic women and risk of cardiovascular events and mortality. JAMA. 2007 Mar 7;297(9):978-85.
cardiovascular disease, electrocardiogram, prediction, outcomesClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17341712https://www.whi.org/researchers/bibliography/Manuscripts/ms387.pdf
Data are sparse regarding the prevalence, incidence, and independent prognostic value of minor and/or major electrocardiographic (ECG) abnormalities in asymptomatic postmenopausal women. There is no information on the effect, if any, of hormonal treatment on the prognostic value of the ECG.To examine association of minor and major baseline and incident ECG abnormalities with long-term cardiovascular morbidity and mortality.Post-hoc analysis of the estrogen plus progestin component of the Women's Health Initiative study, a randomized controlled primary prevention trial of 14 749 postmenopausal asymptomatic women with intact uterus who received 1 daily tablet containing 0.625 mg of oral conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate or a matching placebo. Participants were enrolled from 1993 to 1998, and the estrogen plus progestin trial was stopped on July 7, 2002.The Novacode criteria were used to define minor, major, and incident ECG abnormalities. Cardiovascular end points included incident coronary heart disease (CHD) and cardiovascular disease (CVD) events.Among women with absent (n = 9744), minor (n = 4095), and major (n = 910) ECG abnormalities, there were 118, 91, and 37 incident CHD events, respectively. The incident annual CHD event rates per 10 000 women with absent, minor, or major ECG abnormalities were 21 (95% confidence interval [CI], 18-26), 40 (95% CI, 32-49), and 75 (95% CI, 54-104), respectively. After 3 years of follow-up, 5% of women who had normal ECG at baseline developed new ECG abnormalities with an annual CHD event rate of 85 (95% CI, 44-164) per 10 000 women. The adjusted hazard ratios for CHD events were 1.55 (95% CI, 1.14-2.11) for minor baseline, 3.01 (95% CI, 2.03-4.46) for major baseline, and 2.60 (95% CI, 1.08-6.27) for incident ECG abnormalities. There were no significant interactions between hormone treatment assignment and ECG abnormalities for risk prediction of cardiovascular end points. For prediction of CHD events, the addition of ECG findings to the Framingham risk score increased from 0.69 to 0.74 the area under the receiver operating characteristic curve. Similar findings were found for incident CVD events.Among asymptomatic postmenopausal women, clinically relevant baseline and incident ECG abnormalities are independently associated with increased risk of cardiovascular events and mortality, and the information is incremental to the established method of risk stratification.clinicaltrials.gov Identifier: NCT00000611.
Publication
388
Accuracy of commercial geocoding: Assessment and implicationsEric Whitsel
Whitsel EA, Quibrera PM, Smith RL, Catellier DJ, Liao D, Henley AC, Heiss G. Accuracy of commercial geocoding: Assessment and implications. Epidemiol Perspect Innov. 2006 Jul 20;3:8.
accuracy, Geographic Information Systems, Air Pollution, Cardiovascular DiseasesClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16857050https://www.whi.org/researchers/bibliography/Manuscripts/ms388.pdf
AS140
Published studies of geocoding accuracy often focus on a single geographic area, address source or vendor, do not adjust accuracy measures for address characteristics, and do not examine effects of inaccuracy on exposure measures. We addressed these issues in a Women's Health Initiative ancillary study, the Environmental Epidemiology of Arrhythmogenesis in WHI.Addresses in 49 U.S. states (n = 3,615) with established coordinates were geocoded by four vendors (A-D). There were important differences among vendors in address match rate (98%; 82%; 81%; 30%), concordance between established and vendor-assigned census tracts (85%; 88%; 87%; 98%) and distance between established and vendor-assigned coordinates (mean rho [meters]: 1809; 748; 704; 228). Mean rho was lowest among street-matched, complete, zip-coded, unedited and urban addresses, and addresses with North American Datum of 1983 or World Geodetic System of 1984 coordinates. In mixed models restricted to vendors with minimally acceptable match rates (A-C) and adjusted for address characteristics, within-address correlation, and among-vendor heteroscedasticity of rho, differences in mean rho were small for street-type matches (280; 268; 275), i.e. likely to bias results relying on them about equally for most applications. In contrast, differences between centroid-type matches were substantial in some vendor contrasts, but not others (5497; 4303; 4210) p(interaction) < 10(-4), i.e. more likely to bias results differently in many applications. The adjusted odds of an address match was higher for vendor A versus C (odds ratio = 66, 95% confidence interval: 47, 93), but not B versus C (OR = 1.1, 95% CI: 0.9, 1.3). That of census tract concordance was no higher for vendor A versus C (OR = 1.0, 95% CI: 0.9, 1.2) or B versus C (OR = 1.1, 95% CI: 0.9, 1.3). Misclassification of a related exposure measure--distance to the nearest highway--increased with mean rho and in the absence of confounding, non-differential misclassification of this distance biased its hypothetical association with coronary heart disease mortality toward the null.Geocoding error depends on measures used to evaluate it, address characteristics and vendor. Vendor selection presents a trade-off between potential for missing data and error in estimating spatially defined attributes. Informed selection is needed to control the trade-off and adjust analyses for its effects.
Publication
389
Hierarchical models for the effect of spatial interpolation error on the inferred relationship between ambient particulate matter exposure and cardiovascular healthJames Crooks
Crooks JL, Whitsel E, Catellier DJ, Liao D, Quibrera PM, Smith RL,Hierarchical models for the effect of spatial interpolation error on the inferred relationship between ambient particulate matter exposure and cardiovascular health. Biostatistics (2007), 8, 1; pp. 1–30 doi:10.1093/biostatistics/kxl005 Advance Access publication on May 15, 2006
bias, cardiovascular diseases, air pollutionClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/Ms389.pdf
AS140
Published studies of geocoding accuracy often focus on a single geographic area, address source or vendor, do not adjust accuracy measures for address characteristics, and do not examine effects of inaccuracy on exposure measures. We addressed these issues in a Women's Health Initiative ancillary study, the Environmental Epidemiology of Arrhythmogenesis in WHI.Addresses in 49 U.S. states (n = 3,615) with established coordinates were geocoded by four vendors (A-D). There were important differences among vendors in address match rate (98%; 82%; 81%; 30%), concordance between established and vendor-assigned census tracts (85%; 88%; 87%; 98%) and distance between established and vendor-assigned coordinates (mean rho [meters]: 1809; 748; 704; 228). Mean rho was lowest among street-matched, complete, zip-coded, unedited and urban addresses, and addresses with North American Datum of 1983 or World Geodetic System of 1984 coordinates. In mixed models restricted to vendors with minimally acceptable match rates (A-C) and adjusted for address characteristics, within-address correlation, and among-vendor heteroscedasticity of rho, differences in mean rho were small for street-type matches (280; 268; 275), i.e. likely to bias results relying on them about equally for most applications. In contrast, differences between centroid-type matches were substantial in some vendor contrasts, but not others (5497; 4303; 4210) p(interaction) < 10(-4), i.e. more likely to bias results differently in many applications. The adjusted odds of an address match was higher for vendor A versus C (odds ratio = 66, 95% confidence interval: 47, 93), but not B versus C (OR = 1.1, 95% CI: 0.9, 1.3). That of census tract concordance was no higher for vendor A versus C (OR = 1.0, 95% CI: 0.9, 1.2) or B versus C (OR = 1.1, 95% CI: 0.9, 1.3). Misclassification of a related exposure measure--distance to the nearest highway--increased with mean rho and in the absence of confounding, non-differential misclassification of this distance biased its hypothetical association with coronary heart disease mortality toward the null.Geocoding error depends on measures used to evaluate it, address characteristics and vendor. Vendor selection presents a trade-off between potential for missing data and error in estimating spatially defined attributes. Informed selection is needed to control the trade-off and adjust analyses for its effects.
Publication
390
Identifying risk factors for cognitive change in the Women's Health Initiative Memory Study: a neural networks approachStephan Bandelow
Bandelow S, Espeland MA, Henderson VW, Resnick SM, Wallace RB, Coker LH, Hogervorst E. Identifying risk factors for cognitive change in the Women's Health Initiative: A neural networks approach. In: Hogervorst E, Henderson VW, Gibbs RB, Brinton RD, eds. Hormones, Cognition and Dementia: State of the Art and Emergent Therapeutic Strategies. New York, NY: Cambridge University Press, 2009:11-24.
estrogen treatment, risk assessment, artificial neural networks, dementia, cognitionMemory Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms390.pdf
AS39
Background Hormone therapy (HT) might be beneficial for cognitive function, but the results of recent clinical trials do not support this hypothesis. One of these, the Women’s Health Initiative Memory Study (WHIMS) has been much criticized. It has been suggested that subgroups of women exist for whom HT might improve or impair cognitive function. Methods The multicenter WHIMS had included healthy women over 65 years of age of whom half was randomized to conjugated equine estrogen (CEE) with or without moderoxyprogesterone acetate (MPA), including a separate placebo group for each trial. Based on a literature review, we identified possible mediating variables such as age, smoking, body mass index and symptoms, which could have modified treatment effects. Using artificial neural networks (ANN), which can model higher order non linear interaction testing via hidden units, we tried to identify responders and non responders as defined by changes of 4 points or more on the Modified Mini Mental Status Exam over 4 years, as well as clinical diagnosis. Results The trained neural networks without hidden units could predict the outcomes as well as logistic regression models that included only main effects. Including higher order interactions allowed the ANN models with sufficient hidden unit resources to generate almost perfect outcome classification on the training data. However, ten-fold cross-validation revealed that no improved fit was apparent when the more complex models were tested on novel data, suggesting that the higher-order interactions were spurious. Conclusions There seem to be no subgroups (e.g. older women who smoke and have a high body mass) for whom HT has a worse or better effect on cognitive function over time. Cross validation is essential in building robust models with many independent variables and should be applied as a standard technique in complex multivariate analyses.
Publication
392
Family history of myocardial infarction predicts incident coronary heart disease in postmenopausal women with diabetes: The Women’s Health Initiative Observational StudyRongling Li
Li R, O'Sullivan MJ, Robinson J, Safford MM, Curb D, Johnson KC. Family history of myocardial infarction predicts incident coronary heart disease in postmenopausal women with diabetes: the Women's Health Initiative Observational Study. Diabetes Metab Res Rev. 2009 Nov;25(8):725-32. Epub 2009 Sep 24
family aggregation, macrovascular complication, diabetes, postmenopausal womenObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19780066https://www.whi.org/researchers/bibliography/Manuscripts/ms392.pdf
Diabetes is a risk factor for coronary heart disease (CHD) but CHD does not occur in all diabetic individuals. The goal of this study was to assess the relationship between family history of myocardial infarction (MI) and incident CHD in diabetic postmenopausal women.We conducted a prospective cohort study among 2642 diabetic postmenopausal women without CHD at baseline in the Women's Health Initiative Observational Study. Family history was defined as a proband report of MI in first-degree relatives. Incident CHD was defined as non-fatal MI, coronary revascularization, or CHD death.During 7.3 ( +/- 1.8) years of follow-up, 14.3% of the participants had incident CHD. The risk of incident CHD was 50% higher (HR = 1.50, 95% CI: 1.20-1.87, p = 0.0003) in those with a family history of an MI in at least one first-degree relative, and 79% higher (HR = 1.79, 95% CI: 1.36-2.35, P < 0.0001) if two or more first-degree relatives had an MI, compared to participants without a family history, after adjustment for covariates. The CHD risk increased with elevated systolic blood pressure (SBP) (HR = 1.01, 95% CI: 1.003-1.02, p = 0.001) but decreased with elevated diastolic BP (HR = 0.98, 95% CI: 0.97-0.999, p = 0.005) and with two or more episodes per week of physical activity (HR = 0.70, 95% CI: 0.52-0.93, p = 0.02).The results suggest that a family history of MI predicts CHD in diabetic postmenopausal women. Close attention should be paid to BP control and physical activity in these women.
Publication
394
Association between cigarette smoking and colorectal cancer in the Women's Health InitiativeElectra Paskett
Paskett ED, Reeves KW, Rohan TE, Allison MA, Williams CD, Messina CR, Whitlock E, Sato A, Hunt JR. Association between cigarette smoking and colorectal cancer in the Women's Health Initiative. J Natl Cancer Inst. 2007 Nov 21;99(22):1729-35. Epub 2007 Nov 13.
Smoking, Colorectal CancerBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18000222https://www.whi.org/researchers/bibliography/Manuscripts/ms394.pdf
The evidence linking cigarette smoking to the risk of colorectal cancer is inconsistent. We investigated the associations between active and passive smoking and colorectal cancer among 146,877 Women's Health Initiative participants. Women reported detailed smoking histories at enrollment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between smoking and overall and site-specific risk of colorectal cancer. Invasive colorectal cancer was diagnosed in 1242 women over an average of 7.8 years (range = 0.003-11.2 years) of follow-up. In adjusted analyses, statistically significant positive associations were observed between most measures of cigarette smoking and risk of invasive colorectal cancer. Site-specific analyses indicated that current smokers had a statistically significantly increased risk of rectal cancer (HR = 1.95, 95% CI = 1.10 to 3.47) but not colon cancer (HR = 1.03, 95% CI = 0.77 to 1.38), compared with never smokers. Passive smoke exposure was not associated with colorectal cancer in adjusted analyses. Thus, active exposure to cigarette smoking appears to be a risk factor for rectal cancer.
Publication
395
Effect of hormone therapy on lean body mass, falls, and fractures: 6-year results from the Women's Health Initiative hormone trialsJennifer Bea
Bea JW, Zhao Q, Cauley JA, Lacroix AZ, Bassford T, Lewis CE, Jackson RD, Tylavsky FA, Chen Z. Effect of hormone therapy on lean body mass, falls, and fractures: 6-year results from the Women's Health Initiative hormone trials. Menopause. 2011 Jan;18(1):44-52. doi: 10.1097/gme.0b013e3181e3aab1. Epub 2010 Aug 3.
hormone therapy, lean mass, falling,  fracture, postmenopausal womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/20689466https://www.whi.org/researchers/bibliography/Manuscripts/ms395.pdf
Loss of lean body mass with aging may contribute to falls and fractures. The objective of this analysis was to determine if taking postmenopausal hormone therapy (or HT: estrogen plus progestogen therapy or estrogen therapy alone) favorably affects age-related changes in lean body mass and if these changes partially account for decreased falls or fractures with HT.Participants randomly assigned to either estrogen plus progestogen therapy (n = 543) or control (n = 471) and estrogen therapy alone (n = 453) or control (n = 474) and receiving dual-energy x-ray absorptiometry scans to estimate body composition during the Women's Health Initiative were evaluated. Falls and fracture occurrence were obtained by annual self-report. Fractures were confirmed by a clinical chart review.At 6 years postrandomization, lean body mass was not different between HT and control groups. Although lean body mass positively influenced bone mineral density, independent of HT status, the preserved lean body mass observed in the HT arms in the first 3 years did not significantly contribute to models evaluating HT influence on falls and fractures between years 3 and 6. Women taking at least 80% of their medication in the HT arms demonstrated fewer falls compared with placebo; this difference was not attributable to change in lean body mass.Despite early preservation of lean body mass with HT (3 y), HT did not ameliorate long-term (6 y) loss in lean body mass with aging.
Approved Proposal
397
Is there an association between baseline macronutrient intake and changes in cognition?  Results from the Women’s Health Initiative Memory StudyMara Vitolins
Women’s Health Initiative (WHI); nutrition; cognitive function; postmenopausal; macronutrientsMemory Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms397pv2.pdf
AS39
Publication
398
Osteoporosis and rate of bone loss among postmenopausal survivors of breast cancerZhao Chen
Chen Z, Maricic M, Pettinger M, Ritenbaugh C, Lopez AM, Barad DH, Gass M, Leboff MS, Bassford TL. Osteoporosis and rate of bone loss among postmenopausal survivors of breast cancer. Cancer. 2005 Oct 1;104(7):1520-30.
osteoporosis, bone, loss, postmenopausal, breast cancerObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/16110508https://www.whi.org/researchers/bibliography/Manuscripts/ms398.pdf
Breast cancer diagnosis and treatment may put women at higher risk for osteoporosis in later life.In a subgroup of participants in the Women's Health Initiative Observational Study, authors of the current study investigated differences in bone mineral density (BMD, measured by dual-energy x-ray absorptiometry) between breast cancer survivors (n = 209) and a noncancer reference group (n = 5759).In comparison to the reference group, breast cancer survivors had significantly lower total body BMD value (0.989 vs. 1.013 g/cm(2), P = 0.001) and total hip BMD value (0.823 vs. 0.845 g/cm(2), P = 0.02) at baseline after adjustment for age, race/ethnicity, years since menopause, and clinical center. These lower BMD levels were largely explained by lower usage of hormone therapy (HT) among survivors: after additional statistical adjustment for HT, hip BMD values were 0.834 versus 0.844 g/cm(2) (P = 0.26), and total body values were 1.005 versus 1.013 g/cm(2) (P = 0.33) for survivors and reference women, respectively. More than 77% of survivors with osteoporosis were undiagnosed by their healthcare providers, and this was similar to the undiagnosed rate in the reference group (85.7%). Longitudinally, breast cancer survivors in this study did not demonstrate an accelerated rate of bone loss compared with the reference population.Associated with lower HT usage, postmenopausal survivors of breast cancer were more likely to have low BMD in comparison to other women of the same age; and many of these survivors with osteoporosis were undiagnosed.
Publication
399
Subtypes of mild cognitive impairment in older postmenopausal women: The Women's Health Initiative Memory StudySteve Rapp
Rapp SR, Legault C, Henderson VW, Brunner RL, Masaki K, Jones B, Absher J, Thal L. Subtypes of mild cognitive impairment in older postmenopausal women: The Women's Health Initiative Memory Study. Alzheimer Dis Assoc Disord. 2010 Jul-Sep;24(3):248-55. doi: 10.1097/WAD.0b013e3181d715d5
mild cognitive impairment, hormone therapy, memoryMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/20473134https://www.whi.org/researchers/bibliography/Manuscripts/ms399.pdf
AS39
Mild cognitive impairment (MCI) is a transitional state between normal cognitive functioning and dementia. A proposed MCI typology classifies individuals by the type and extent of cognitive impairment, yet few studies have characterized or compared these subtypes. Four hundred forty-seven women 65 years of age and older from the Women's Health Initiative Memory Study were classified into the 4 MCI subgroups and a "no impairment" group and compared on clinical, sociodemographic, and health variables. A cognitive deficit in at least 1 domain was present in 82.1% of participants, with most (74.3%) having deficits in multiple cognitive domains. Only 4.3% had an isolated memory deficit, whereas 21.3% had an isolated nonmemory deficit. Of the 112 women who met all MCI criteria examined, the most common subtype was amnestic multidomain MCI (42.8%), followed by nonamnestic multiple domain MCI (26.7%), nonamnestic single domain (24.1%), and amnestic single domain MCI (6.3%). Subtypes were similar with respect to education, health status, smoking, depression, and prestudy and onstudy use of hormone therapy. Despite the attention it receives in the literature, amnestic MCI is the least common type highlighting the importance of identifying and characterizing other nonamnestic and multidomain subtypes. Further research is needed on the epidemiology of MCI subtypes, clinical and biologic differences between them, and rates for conversion to dementia.
Publication
401
Are depressive symptoms associated with cancer screening and cancer stage at diagnosis among postmenopausal women? The Women’s Health Initiative Observational CohortArpita Aggarwal
Aggarwal A, Freund K, Sato A, Adams-Campbell LL, Lopez AM, Lessin LS, Ockene J, Wallace RB, Williams CD, Bonds DE. Are depressive symptoms associated with cancer screening and cancer stage at diagnosis among postmenopausal women? The Women’s Health Initiative Observational Cohort. J Womens Health (Larchmt). 2008 Oct;17(8):1353-61. Epub 2008 Sep 14.
breast cancer, colorectal cancer, mammography, colonoscopy, sigmoidoscopy, screening, women, depressionObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18788983https://www.whi.org/researchers/bibliography/Manuscripts/ms401.pdf
Women with depressive symptoms may use preventive services less frequently and experience poorer health outcomes. We investigated the association of depressive symptoms with breast and colorectal cancer screening rates and stage of cancer among a cohort of postmenopausal women.In The Women's Health Initiative Observational Study, 93,676 women were followed on average for 7.6 years. Depressive symptoms were measured at baseline and at 3 years using the 6-item scale from the Center for Epidemiological Studies Depression scale (CES-D). We calculated a cancer screening rate expressed as a proportion of the years that women were current with recommended cancer screening over the number of follow-up visits in the study. Breast and colorectal cancers were staged based on Surveillance, Epidemiology and End Results (SEER) classification.At baseline, 15.8% (12,621) women were positive for depressive symptoms, and 6.9% (4,777) were positive at both baseline screening and at 3 years. The overall average screening rate was 71% for breast cancer and 53% for colorectal cancer. The breast cancer screening rate was 1.5% (CI 0.9%-2.0%) lower among women who reported depressive symptoms at baseline than among those who did not. Depressive symptoms were not a predictor for colorectal cancer screening. Stage of breast and colorectal cancer was not found to be associated with depressive symptoms after adjusting for covariates.Among a healthy and self-motivated cohort of women, self-reported depressive symptoms were associated with lower rates of screening mammography but not with colorectal cancer screening.
Publication
402
Subclinical hypothyroidism and risk for incident myocardial infarction among postmenopausal womenVicky LeGrys
Legrys VA, Funk MJ, Lorenz CE, Giri A, Jackson RD, Manson JE, Schectman R, Edwards TL, Heiss G, Hartmann KE. Subclinical hypothyroidism and risk for incident myocardial infarction among postmenopausal women. J Clin Endocrinol Metab. 2013 Jun;98(6):2308-17. doi: 10.1210/jc.2012-4065. Epub 2013 Mar 28.
hypothyroidism, myocardial infaction, postmenopuase, nested case-cohort analysis, WHI OS, thyroid diseases, TSH, TPOAb, FT4Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/23539723https://www.whi.org/researchers/bibliography/Manuscripts/Ms402.pdf
AS165
Subclinical hypothyroidism (SCH) has been associated with an increased risk for cardiovascular disease. However, few studies have specifically examined the association between SCH and myocardial infarction (MI), and the relationship is poorly understood.The purpose of this study was to evaluate incident MI risk in relation to SCH and severities of SCH among postmenopausal women.We used a population-based nested case-cohort design within the Women's Health Initiative observational study to examine the association between SCH and incident first-time MI risk among postmenopausal women in the United States. SCH was assessed using blood specimens collected at baseline. Participants presenting with normal free T4 levels and with thyrotropin levels of greater than 4.68-6.99 mU/L or 7.00 mU/L or greater were defined as having mild SCH or moderate/severe SCH, respectively. MI cases were centrally adjudicated by trained Women's Health Initiative staff. The primary analysis included 736 incident MI cases and 2927 randomly selected subcohort members. Multivariable adjusted Cox-proportional hazard models were used to assess MI risk in relation to SCH.Compared with euthyroid participants, the multivariable adjusted hazard ratio (HR) for participants with any SCH was 1.05 [95% confidence interval (CI) 0.77-1.44]. HRs for participants with mild SCH, moderate/severe SCH, and moderate/severe SCH and the presence of antithyroid peroxidase antibodies (TPOAb) were 0.99 (95% CI 0.67-1.46), 1.19 (95% CI 0.72-1.96), and 0.90 (95% CI 0.47-1.74), respectively.We did not find evidence to suggest that SCH is associated with increased MI risk among a population of predominantly older postmenopausal women with no prior history of MI.
Publication
403
Subclinical hypothyroidism and risk for incident ischemic stroke among postmenopausal womenAyush Giri
Giri A, Edwards TL, LeGrys VA, Lorenz CE, Jonsson Funk M, Schectman R, Heiss G, Robinson JG, Hartmann KE. Subclinical hypothyroidism and risk for incident ischemic stroke among postmenopausal women. Thyroid. 2014 Aug;24(8):1210-7. doi: 10.1089/thy.2014.0106. Epub 2014 Jun 16
hypothyroidism, myocardial infaction, postmenopuase, nested case-cohort analysis, WHI OS, thyroid diseases, TSH, TPOAb, FT4Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/24827923https://www.whi.org/researchers/bibliography/Manuscripts/Ms403.pdf
AS165
Subclinical hypothyroidism (SCH) is postulated to increase stroke risk via atherogenic changes associated with abnormal thyroid function. However, the direct relationship of SCH with subsequent stroke is poorly studied.In this nested case-cohort study, we prospectively evaluated the association between any SCH and severity of SCH in relation to incident ischemic stroke risk among postmenopausal women in the Women's Health Initiative Observational Study. Trained Women's Health Initiative staff, masked to thyroid status, adjudicated stroke cases. We assessed thyroid function using baseline blood specimens. Women with normal free thyroxine levels and thyrotropin (TSH) levels ≥4.69 mU/L were considered to have SCH. Primary analysis included 639 ischemic stroke cases and 2927 randomly selected subcohort members with an average of seven years of follow-up.The multivariable adjusted hazard ratios (HR) from weighted Cox models were 1.06 (95% confidence interval [CI]: 0.77, 1.46) and 0.99 (95% CI: 0.67, 1.47) for women with any SCH and with mild SCH (TSH 4.69 to 6.99 mU/L), when compared with women with normal thyroid function. The HR for moderate/severe SCH (TSH ≥7.00 mU/L) was modestly elevated (HR: 1.22; 95% CI: 0.73, 2.05).We found no evidence to suggest an association between SCH and ischemic stroke among healthy postmenopausal women.
Publication
404
Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: Results from the Women's Health InitiativeZhao Chen
Chen Z, Maricic M, Aragaki AK, Mouton C, Arendell L, Lopez AM, Bassford T, Chlebowski RT. Fracture risk increases after diagnosis of breast or other cancers in postmenopausal women: Results from the Women's Health Initiative. Osteoporos Int. 2009 Apr;20(4):527-36. Epub 2008 Sep 3.
incident breast cancer, fracture risk, falling, incident cancer, postmenopausalBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18766294https://www.whi.org/researchers/bibliography/Manuscripts/ms404.pdf
Risk for falls and fractures increases after breast cancer or other cancer diagnosis in postmenopausal women. Factors other than falls may be the major causes for the increased fracture risk.Cancer treatment and prognosis may have detrimental effects on bone health. However, there is a lack of prospective investigations on fracture risk among incident cancer cases.In this study, postmenopausal women (N = 146,959) from the Women's Health Initiative prospective cohort, who had no cancer history at baseline, were followed for up to 9 years and classified into no cancer, incident breast cancer (BC) and incident other cancer (OC) groups. The main outcomes measured were incident fractures and falls before and after cancer diagnosis. Hazards ratios (HR) and 95% confidence intervals (CI) were computed from Cox proportional hazards model.While hip fracture risk before a cancer diagnosis was similar between the no cancer and cancer groups, hip fracture risk was significantly higher after BC diagnosis (HR = 1.55, CI = 1.13-2.11) and the elevated risk was even more notable after OC diagnosis (HR = 2.09, CI = 1.65-2.65). Risk of falls also increased after BC (HR = 1.15, CI = 1.06-1.25) or OC diagnosis (HR = 1.27, CI = 1.18-1.36), but could not fully explain the elevated hip fracture risk. Incident clinical vertebral and total fractures were also significantly increased after OC diagnosis (p < 0.05).Postmenopausal women have significantly elevated risks for falls and fractures after a cancer diagnosis. The causes for this increased risk remained to be investigated.
Approved Manuscript
405
Body image in postmenopausal women as it relates to diet, exercise, smoking, ethnicity, socioeconomic status and age: WHID. Marie Jackson
body image, body dissatisfaction, body perception, body shape perception, ideal figureObservational Study
Publication
409
Clinical risk factors for fractures in multi-ethnic women: The Women's Health InitiativeJane Cauley
Cauley JA, Wu L, Wampler NS, Barnhart JM, Allison M, Chen Z, Jackson R, Robbins J. Clinical risk factors for fractures in multi-ethnic women: The Women's Health Initiative. J Bone Miner Res. 2007 Nov;22(11):1816-26.
osteoporosis, fractures, risk factors, minority women, race/ethnicity, womenObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17638574https://www.whi.org/researchers/bibliography/Manuscripts/ms409.pdf
To identify risk factors for fractures in multi-ethnic women, we studied 159,579 women enrolled in the Women's Health Initiative. In general, risk factors for fractures were similar across ethnic groups. However, irrespective of their ethnicity, women with multiple risk factors have a high risk of fracture. Targeting these high-risk women for screening and intervention could reduce fractures.Fracture rates tend to be lower in minority women, but consequences may be greater. In addition, the number of fractures is expected to increase in minority women because of current demographic trends. There are limited prospective data on risk factors for fractures in minority women.We studied 159,579 women 50-79 yr of age enrolled in the Women's Health Initiative. Information on risk factors was obtained by questionnaire or examination. Nonspine fractures that occurred after study entry were identified over an average follow-up of 8 +/- 2.6 (SD) yr.Annualized rates (%) of fracture in whites, blacks, Hispanics, Asians, and American Indians were 2.0, 0.9, 1.3, 1.2, and 2.0, respectively. Significant predictors [HR (95% CI)] of fractures by ethnic group were as follows: blacks: at least a high school education, 1.22 (1.0, 1.5); (+) fracture history, 1.7 (1.4, 2.2); and more than two falls, 1.7 (1.9, 2.0); Hispanics: height (>162 cm), 1.6 (1.1, 2.2); (+) fracture history, 1.9 (1.4, 2.5); more than two falls, 1.8 (1.4, 2.3); arthritis, 1.3 (1.1, 1.6); corticosteroid use, 3.9 (1.9, 8.0); and parental history of fracture, 1.3 (1.0, 1.6); Asians: age (per 5 yr), 1.2 (1.0, 1.3); (+) fracture history, 1.5 (1.1, 2.0); current hormone therapy (HT), 0.7 (0.5, 0.8); parity (at least five), 1.8 (1.1, 3.0); more than two falls, 1.4 (1.1, 1.9); American Indian: (+) fracture history, 2. 9 (1.5, 5.7); current HT, 0.5 (0.3, 0.9). Women with eight or more risk factors had more than a 2-fold higher rate of fracture compared with women with four or fewer risk factors. Two ethnicity x risk factor interactions were identified: age and fall history.Irrespective of their ethnicity, women with multiple risk factors have a high risk of fracture. Targeting these high-risk women for screening and intervention could reduce fractures.
Approved Manuscript
410
Psychological factors and late-stage breast, colorectal, and endometrial cancer: the Women’s Health Initiative Observational CohortRowan Chlebowski
stressful life events, breast cancer, health disparities, social supportObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms410v2.pdf
Approved Proposal
412
Validation of WHO model for absolute risk of fractureJane Cauley
osteoporotic range, t scores, BMDBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms412p.pdf
Publication
414
Prehypertension and cardiovascular disease risk in the Women's Health InitiativeJudith Hsia
Hsia J, Margolis KL, Eaton CB, Wenger NK, Allison M, Wu L, LaCroix AZ, Black HR, Women's Health Initiative Investigators. Prehypertension and cardiovascular disease risk in the Women's Health Initiative. Circulation. 2007 Feb 20;115(7):855-60.
Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17309936https://www.whi.org/researchers/bibliography/Manuscripts/Ms414.pdf
Prehypertension is common and is associated with increased vascular mortality. The extent to which it increases risk of nonfatal myocardial infarction, stroke, and congestive heart failure is less clear.We determined the prevalence of prehypertension, its association with other coronary risk factors, and the risk for incident cardiovascular disease events in 60,785 postmenopausal women during 7.7 years of follow-up using Cox regression models that included covariates as time-dependent variables. Prehypertension was present at baseline in 39.5%, 32.1%, 42.6%, 38.7%, and 40.3% of white, black, Hispanic, American Indian, and Asian women, respectively (P<0.0001 across ethnic groups). Age, body mass index, and prevalence of diabetes mellitus and hypercholesterolemia increased across blood pressure categories, whereas smoking decreased (all P<0.0001). Compared with normotensive women (referent), adjusted hazard ratios for women with prehypertension were 1.58 (95% confidence interval [CI], 1.12 to 2.21) for cardiovascular death, 1.76 (95% CI, 1.40 to 2.22) for myocardial infarction, 1.93 (95% CI, 1.49 to 2.50) for stroke, 1.36 (95% CI, 1.05 to 1.77) for hospitalized heart failure, and 1.66 (95% CI, 1.44 to 1.92) for any cardiovascular event. Hazard ratios for the composite outcome with prehypertension did not differ between ethnic groups (P=0.71 for interaction), although the numbers of events among Hispanic and Asian women were small.Prehypertension is common and was associated with increased risk of myocardial infarction, stroke, heart failure, and cardiovascular death in white and nonwhite postmenopausal women. Risk factor clustering was conspicuous, emphasizing the need for trials evaluating the efficacy of global cardiovascular risk reduction through primordial prevention.
Publication
415
GIS approaches for the estimation of residential-level ambient PM concentrationsDuanping Liao
Liao D, Peuquet DJ, Duan Y, Whitsel EA, Dou J, Smith RL, Lin HM, Chen JC, Heiss G. GIS approaches for the estimation of residential-level ambient PM concentrations. Environ Health Perspect. 2006 Sep;114(9):1374-80.
Geographic Information Systems, Kriging, Cross-Validation, Air Pollution.Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16966091https://www.whi.org/researchers/bibliography/Manuscripts/ms415.pdf
AS140
Spatial estimations are increasingly used to estimate geocoded ambient particulate matter (PM) concentrations in epidemiologic studies because measures of daily PM concentrations are unavailable in most U.S. locations. This study was conducted to a) assess the feasibility of large-scale kriging estimations of daily residential-level ambient PM concentrations, b) perform and compare cross-validations of different kriging models, c) contrast three popular kriging approaches, and d) calculate SE of the kriging estimations. We used PM data for PM with aerodynamic diameter </= 10 microm (PM10) and aerodynamic diameter </= 2.5 microm (PM2.5) from the U.S. Environmental Protection Agency for the year 2000. Kriging estimations were performed at 94,135 geocoded addresses of Women's Health Initiative study participants using the ArcView geographic information system. We developed a semiautomated program to enable large-scale daily kriging estimation and assessed validity of semivariogram models using prediction error (PE) , standardized prediction error (SPE) , root mean square standardized (RMSS) , and SE of the estimated PM. National- and regional-scale kriging performed satisfactorily, with the former slightly better. The average PE, SPE, and RMSS of daily PM10 semivariograms using regular ordinary kriging with a spherical model were 0.0629, -0.0011, and 1.255 microg/m3, respectively ; the average SE of the estimated residential-level PM10 was 27.36 microg/m3. The values for PM2.5 were 0.049, 0.0085, 1.389, and 4.13 microg/m3, respectively. Lognormal ordinary kriging yielded a smaller average SE and effectively eliminated out-of-range predicted values compared to regular ordinary kriging. Semiautomated daily kriging estimations and semivariogram cross-validations are feasible on a national scale. Lognormal ordinary kriging with a spherical model is valid for estimating daily ambient PM at geocoded residential addresses.
Publication
416
Influence of estrogen plus testosterone supplementation on breast cancerRoberta Ness
Ness RB, Albano JD, McTiernan A, Cauley JA. Influence of estrogen plus testosterone supplementation on breast cancer. Arch Intern Med. 2009 Jan 12;169(1):41-6
androgens, breast cancerObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19139322https://www.whi.org/researchers/bibliography/Manuscripts/ms416.pdf
Concern that the use of exogenous testosterone may increase breast cancer risk coexists with rising use of this medication in the United States. We sought to examine the relationship between the use of estrogen plus testosterone (E + T) therapy (esterified estradiol plus methyltestosterone) and the occurrence of breast cancer.A total of 31,842 postmenopausal participants in the Women's Health Initiative Observational Study were followed for a mean of 4.6 years. At the 3-year visit, E + T users were compared with non-hormone therapy users for time to incident invasive breast cancer. Cox proportional hazards estimates were adjusted for known predictors of breast cancer including prior hormone use and screening mammography.Thirty five women using E + T at visit 3 developed invasive breast cancer. Use of E + T had a nonsignificant impact on invasive breast cancer risk (adjusted hazard ratio, 1.42; 95% confidence interval, 0.95-2.11). The most commonly used E + T preparation, Estratest, was associated with a significant elevation in invasive breast cancer (adjusted hazard ratio, 1.78; 95% confidence interval, 1.05-3.01). However, rates of breast cancer were lower in longer-term E + T users than in shorter-term E + T users.Although our results have less strength than an initial report linking E + T to breast cancer, we found a modest, albeit nonsignificant, elevation in breast cancer risk associated with E + T use.
Publication
417
Impact of cyclooxygenase inhibitors in the Women's Health Initiative Hormone Trials: Secondary analysis of a randomized trialJudith Hsia
Hsia J, Manson JE, Kuller L, Pettinger M, Choe JH, Langer RD, Limacher M, Oberman A, Ockene J, O'Sullivan MJ, Robinson JG. Impact of cyclooxygenase inhibitors in the Women's Health Initiative Hormone Trials: Secondary analysis of a randomized trial. PLoS Clin Trials. 2006 Sep 29;1(5):e26.
 COX-2 inhibition , CHDClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17016543https://www.whi.org/researchers/bibliography/Manuscripts/Ms417.pdf
We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials.The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6.The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States.The trials enrolled 27,347 postmenopausal women, aged 50-79 y.We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo.Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial.Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified.Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results.
Publication
418
Linear measurement error models with restricted samplingMalka Gorfine
Gorfine M, Lipshtat N, Freedman LS, Prentice RL. Linear measurement error models with restricted sampling. Biometrics. 2007 Mar;63(1):137-42.
measurement error, restricted sampling, multiple imputation, longitudinal data, nutritional epidemiology, biomarkerClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17447938https://www.whi.org/researchers/bibliography/Manuscripts/ms418.pdf
The relationship between nutrient consumption and chronic disease risk is the focus of a large number of epidemiological studies where food frequency questionnaires (FFQ) and food records are commonly used to assess dietary intake. However, these self-assessment tools are known to involve substantial random error for most nutrients, and probably important systematic error as well. Study subject selection in dietary intervention studies is sometimes conducted in two stages. At the first stage, FFQ-measured dietary intakes are observed and at the second stage another instrument, such as a 4-day food record, is administered only to participants who have fulfilled a prespecified criterion that is based on the baseline FFQ-measured dietary intake (e.g., only those reporting percent energy intake from fat above a prespecified quantity). Performing analysis without adjusting for this truncated sample design and for the measurement error in the nutrient consumption assessments will usually provide biased estimates for the population parameters. In this work we provide a general statistical analysis technique for such data with the classical additive measurement error that corrects for the two sources of bias. The proposed technique is based on multiple imputation for longitudinal data. Results of a simulation study along with a sensitivity analysis are presented, showing the performance of the proposed method under a simple linear regression model.
Publication
420
Postmenopausal hormone use and the risk of nephrolithiasis: Results from the Women’s Health Initiative hormone therapy trialsNaim Maalouf
Maalouf NM, Sato AH, Welch BJ, Howard BV, Cochrane BB, Sakhaee K, Robbins JA. Postmenopausal hormone use and the risk of nephrolithiasis: Results from the Women’s Health Initiative hormone therapy trials. Arch Intern Med. 2010;170(18):1678-1685
estrogen, hormone replacement, nephrolithiasis, kidney stone disease, menopauseClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/20937929https://www.whi.org/researchers/bibliography/Manuscripts/Ms420.pdf
Observational studies examining the role of estrogen in the risk of kidney stone formation have shown conflicting results. However, randomized trial evidence on nephrolithiasis risk with estrogen therapy in postmenopausal women is lacking.We reviewed the incidence of nephrolithiasis in the Women's Health Initiative estrogen-alone and estrogen plus progestin trials conducted at 40 US clinical centers. A total of 10 739 postmenopausal women with hysterectomy were randomized to receive 0.625 mg/d of conjugated equine estrogens (CEE) or placebo, and 16 608 postmenopausal women without hysterectomy were randomized to receive placebo or estrogen plus progestin given as CEE plus medroxyprogesterone acetate (2.5 mg/d). The incidence of nephrolithiasis was determined for an average follow-up of 7.1 years for the CEE trial and 5.6 years for the estrogen plus progestin trial.Baseline demographic characteristics and risk factors for nephrolithiasis were similar in the placebo and treatment arms. Estrogen therapy was associated with a significant increase in nephrolithiasis risk from 34 to 39 cases per 10 000 person-years (hazard ratio, 1.21; 95% confidence interval, 1.03-1.44). Censoring data from women when they ceased to adhere to study medication increased the hazard ratio to 1.39 (95% confidence interval, 1.08-1.78). The increased nephrolithiasis risk was independent of progestin coadministration, and effects did not vary significantly according to prerandomization history of nephrolithiasis.These data suggest that estrogen therapy increases the risk of nephrolithiasis in healthy postmenopausal women. These findings should be considered in decision making regarding postmenopausal estrogen use. The mechanisms underlying this higher susceptibility remain to be determined. Trial Registration clinicaltrials.gov Identifier: NCT0000611.
Publication
421
Serum alpha-tocopherol, concurrent and past vitamin E intake, and mild cognitive impairmentJulie Dunn
Dunn JE, Weintraub S, Stoddard AM, Banks S. Serum alpha-tocopherol, concurrent and past vitamin E intake, and mild cognitive impairment. Neurology. 2007 Feb 27;68(9):670-6.
cognitive function, antioxidant nutrients, vitamin e, alpha tocopherol, diet, supplements, serum, memoryBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/17325274https://www.whi.org/researchers/bibliography/Manuscripts/ms421.pdf
AS84
Associations of past dietary vitamin E intake, past and current vitamin E supplement use, and current serum alpha-tocopherol levels, with memory (amnestic) and mixed-domain cognitive impairment in older women, ascertained from an in-depth neuropsychological assessment, were explored.This analysis used baseline data from 526 participants in a single-site ancillary study to the Women's Health Initiative, the Cognitive Change in Women study.In bivariate analyses, neither past dietary vitamin E intake (<8 mg/day vs more) nor current vitamin E supplement use was associated with impairment. Women who did not use vitamin E supplements at Women's Health Initiative baseline had an increased risk of mixed-domain impairment (odds ratio [OR] 1.88; 95% CI 1.09 to 3.23). This association lost significance when adjusting for age, education, American National Adult Reading Test (ANART) score, and time between measurement of past vitamin E use and cognitive testing. Concurrent serum alpha-tocopherol had significant cross-sectional associations with both memory and mixed impairments, with women in the lowest quartile of serum alpha-tocopherol nearly twice as likely to show signs of memory (1.92; 1.24 to 2.97) and mixed-domain (2.01; 1.13 to 3.57) impairments. In multivariable models adjusting for age, education, and ANART score, the lowest quartile of serum alpha-tocopherol was associated with increased odds of memory impairment (OR 2.02; 1.27 to 3.20) and mixed impairments (OR 2.00; 1.04 to 3.85). Additional adjustment for APOE e4 did not affect these results.There was weak or no evidence of a protective effect of previous vitamin E intake on cognitive function. However, the association of low concurrent serum alpha-tocopherol with memory and mixed impairment merits further exploration.
Publication
422
Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women's Health Initiative observational studyMary Pressler
Pressler M, Rosenberg CA, Derman BA, Greenland P, Khandekar J, Rodabough RJ, McTiernan A, Simon MS. Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women's Health Initiative observational study. Breast Cancer Res Treat. 2013 Jun;139(3):821-31. doi: 10.1007/s10549-013-2578-y. Epub 2013 Jun 13.
none providedObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/23760856https://www.whi.org/researchers/bibliography/Manuscripts/Ms422.pdf
An increased risk of breast cancer has been reported in patients with non-melanomatous skin cancer (NMSC), but this association has not been studied in a large, multi-geographic population. We utilized data from the Women's Health Initiative observational study to assess whether history of NMSC is associated with breast cancer risk. This analysis included 70,246 postmenopausal White and Hispanic women aged 50-79, in which 4,247 breast cancer cases were identified over a mean (SD) of 11.3 (3.2) years. Baseline information was collected on demographics, medical history, sun exposure, and vitamin D intake. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs). The relationship between NMSC and breast cancer was examined as a time-dependent exposure using updated information on NMSC gathered during follow-up visits. All statistical tests were two sided. There were 5,595 women diagnosed with NMSC at study entry. The annualized rate of breast cancer was 0.64 % among women with a history of NMSC and 0.55 % among women with no history of NMSC. The multivariable-adjusted HR for breast cancer among women with a history of NMSC versus no history of NMSC was 1.07 (95 % CI 0.95-1.20, P = 0.27). Further evaluation stratified by tumor characteristics showed an increased risk of lymph node-positive disease, HR = 1.30 (95 % CI 1.01-1.67, P = 0.04), and regional-stage disease, HR = 1.33 (95 % CI 1.05-1.70, P = 0.02), among women with NMSC. There was no significant overall association between NMSC and breast cancer; however, there was an increased risk of more advanced-stage breast cancer which needs further exploration.
Publication
423
Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular diseaseRoss Prentice
Prentice RL, Langer RD, Stefanick ML, Howard BV, Pettinger M, Anderson GL, Barad D, Curb JD, Kotchen J, Kuller L, Limacher M, Wactawski-Wende J, Women's Health Initiative Investigators. Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease. Am J Epidemiol. 2006 Apr 1;163(7):589-99. Epub 2006 Feb 16.
body mass index, cardiovascular disease, deep vein thrombosis, hormone treatment,  myocardial infarction, pulmonary embolismBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/16484450https://www.whi.org/researchers/bibliography/Manuscripts/ms423.pdf
Circumstances in which both randomized controlled trial and observational study data are available provide an important opportunity to identify biases and improve study design and analysis procedures. In addition, joint analyses of data from the two sources can extend clinical trial findings. The US Women's Health Initiative includes randomized controlled trials of use of estrogen by posthysterectomy women and of estrogen plus progestin by women with a uterus, along with corresponding observational study components. In this paper, for coronary heart disease, stroke, and venous thromboembolism, results are first presented from joint analysis of estrogen clinical trial and observational study data to show that residual bias patterns are similar to those previously reported for estrogen plus progestin. These findings support certain combined analyses of the observational data on estrogen and the estrogen plus progestin clinical trial and observational study data to give adjusted observational study estimates of estrogen treatment effects. The resulting treatment effect estimates are compared with corresponding clinical trial estimates, and parallel analyses are also presented for estrogen plus progestin. An application to postmenopausal hormone treatment effects on coronary heart disease among younger women is also provided.
Publication
426
Incident invasive breast cancer, geographic location of residence, and reported average time spent outsideAmy Millen
Millen AE, Pettinger M, Freudenheim JL, Langer RD, Rosenberg CA, Mossavar-Rahmani Y, Duffy CM, Lane DS, McTiernan A, Kuller LH, Lopez AM, Wactawski-Wende J. Incident invasive breast cancer, geographic location of residence, and reported average time spent outside. Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):495-507. Epub 2009 Feb 3.
breast cancer, geography, sunlight, risk factors, socioeconomic status, dietObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19190147https://www.whi.org/researchers/bibliography/Manuscripts/ms426.pdf
There have been reports of greater breast cancer incidence and mortality at northern compared with southern latitudes postulated to be related to vitamin D exposure. Among 71,662 participants in the Women's Health Initiative Observational Study (WHIOS) free of cancer at baseline (1993-1998), associations were explored between incident invasive postmenopausal breast cancer (n = 2,535), over approximately 8.6 years follow-up, and the following: (a) region of residence at birth, age 15 years, age 35 years; (b) region of residence at WHIOS baseline; and (c) clinic center solar irradiance. Hazard ratios and 95% confidence intervals (CI) for breast cancer were estimated after adjustment for individual level confounders. There was no difference in breast cancer risk by region of earlier life, baseline residence, or solar irradiance measured in Langelys (gm-cal) per cm(2). There was an observed 15% decreased risk among women residing in areas of low versus high solar irradiance measured in Watts per m(2) (95% CI, 2-26%). However, the associated P(trend) of 0.20 was not significant. Conversely, women who reported spending on average <30 minutes versus >2 hours outside in daylight year round at WHIOS year 4 follow-up (n = 46,926), had a 20% (95% CI, 2-41%; P(trend) = 0.001) increased risk of breast cancer. In conclusion, region of residence and geographic solar irradiance are not consistently related to risk of breast cancer and may not be sufficient proxy measures for sunlight/vitamin D exposure. The observed association between time spent outside and breast cancer risk support the hypothesis that vitamin D may protect against breast cancer.
Approved Proposal
427
Statin use and cognition in postmenopausal women: The Women’s Health Initiative Memory StudyClaudine Legault
menopause, statins, hormone therapy, cognition, dementiaClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/ms427pv2.pdf
AS39
Publication
428
Association of pelvic organ prolapse and fractures in postmenopausal women: Analysis of baseline data from the Women's Health Initiative Estrogen plus Progestin TrialLubna Pal
Pal L, Hailpern SM, Santoro NF, Freeman R, Barad D, Kipersztok S, Barnabei VM, Wassertheil-Smoller S. Association of pelvic organ prolapse and fractures in postmenopausal women: Analysis of baseline data from the Women's Health Initiative Estrogen Plus Progestin trial. Menopause. 2008 Jan-Feb;15(1):59-66.
Pelvic organ prolapse, postmenopause, Fracture, Women's health InitiativeBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18257143https://www.whi.org/researchers/bibliography/Manuscripts/ms428.pdf
Testing a hypothesis that pelvic organ prolapse (POP) is a focal manifestation of disordered connective tissue, we evaluated whether there is an association between POP and history of fracture.This was a case-control study. Baseline data were from postmenopausal women aged 60 years or older enrolled in the Women's Health Initiative Estrogen Plus Progestin trial. Distinct variants (cystocele, rectocele, and uterovaginal) and severity (mild, moderate, or severe) of POP were recognized. A history of "fracture after age 55" was considered as the event of interest.Moderate to severe POP was identified in 9% of 11,096 participants aged 60 years or older. Women with moderate to severe rectocele were significantly more likely to report fracture (odds ratio: 1.37, 95% CI: 1.06-1.77, P = 0.02) compared with those with absent to mild prolapse. Of the subset of participants who underwent bone mineral density assessment, those with moderate to severe prolapse demonstrated significantly lower whole-body bone mineral density ([beta] = -0.03, SE 0.02); this difference was of borderline significance (P = 0.05) compared with that for participants with absent to mild POP. Multivariate logistic regression analysis confirmed an independent association between moderate to severe rectocele and fracture (odds ratio: 1.45, 95% CI: 1.08-1.95, P = 0.01).We demonstrate a relationship between moderate to severe POP and low bone mineral density in postmenopausal women enrolled in the Women's Health Initiative Estrogen Plus Progestin trial. Our findings of an association between clinically significant (moderate to severe) POP, specifically rectocele, and a history of fracture suggest that suboptimal collagen status purported to associate with POP may also involve bone collagen and hence translate into skeletal compromise.
Publication
429
Can biomarkers identify women at increased stroke risk? The Women's Health Initiative Hormone TrialsCharles Kooperberg
Kooperberg C, Cushman M, Hsia J, Robinson J, Aragaki A, Lynch J, Baird A, Johnson K, Kuller L, Beresford S, Rodriguez B. Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials. PLoS Clin Trials 2007; 2(6): e28.
stroke, hormone therapy, inflammation, thrombosis, lipidsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/17571161https://www.whi.org/researchers/bibliography/Manuscripts/ms429.pdf
W6
The Women's Health Initiative hormone trials identified a 44% increase in ischemic stroke risk with combination estrogen plus progestin and a 39% increase with estrogen alone. We undertook a case-control biomarker study to elucidate underlying mechanisms, and to potentially identify women who would be at lower or higher risk for stroke with postmenopausal hormone therapy (HT).The hormone trials were randomized, double-blind, and placebo controlled.The Women's Health Initiative trials were conducted at 40 clinical centers in the United States.The trials enrolled 27,347 postmenopausal women, aged 50-79 y.We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo.Stroke was ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial.No baseline clinical characteristics, including gene polymorphisms, identified women for whom the stroke risk from HT was higher. Paradoxically, women with higher baseline levels of some stroke-associated biomarkers had a lower risk of stroke when assigned to estrogen plus progestin compared to placebo. For example, those with higher IL-6 were not at increased stroke risk when assigned to estrogen plus progestin (odds ratio 1.28) but were when assigned to placebo (odds ratio 3.47; p for difference = 0.02). Similar findings occurred for high baseline PAP, leukocyte count, and D-dimer. However, only an interaction of D-dimer during follow-up interaction with HT and stroke was marginally significant (p = 0.03).Biomarkers did not identify women at higher stroke risk with postmenopausal HT. Some biomarkers appeared to identify women at lower stroke risk with estrogen plus progestin, but these findings may be due to chance.
Publication
430
Sleep duration and risk of ischemic stroke in postmenopausal womenJiu-Chiuan Chen
Chen JC, Brunner RL, Ren H, Wassertheil-Smoller S, Larson JC, Levine DW, Allison M, Naughton MJ, Stefanick ML.  Sleep duration and risk of ischemic stroke in postmenopausal women. Stroke. 2008 Dec;39(12):3185-92. doi: 10.1161/STROKEAHA.108.521773. Epub 2008 Jul 17
 insomnia, cardiovascular diseases, risk factors, inflammation mediators, endocrine system, women’s healthBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18635832https://www.whi.org/researchers/bibliography/Manuscripts/ms430.pdf
AS140, AS39
Many studies have shown a U-shape association between sleep duration and mortality, but epidemiological evidence linking cardiovascular diseases with habitual sleep patterns is limited and mixed.We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Women's Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics.At baseline, 8.3% of subjects had reported their sleep duration as <or=5 hours per night and 4.6% reported long duration of sleep (>or=9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting <or=6, 8, and >or=9 hours of sleep. A modestly stronger association with sleep duration <or=6 hours per night (RR, 1.22; 1.03, 1.44) was noted among women without prevalent cardiovascular disease at baseline. Our analyses also reveal that the adverse effect of long sleep is likely independent of the increased risk for ischemic stroke associated with frequent snoring and sleepiness (RR, 1.31; 1.00, 1.72).Habitual sleep patterns are important neurobehavioral determinants of risk for ischemic stroke in postmenopausal women. The underlying neurobiology and mechanistic mediators for the putative adverse effect of long sleep (>or=9 hours/night) need further elucidation.
Publication
432
Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal womenKathleen McTigue
McTigue KM, Chang YF, Eaton C, Garcia L, Johnson KC, Lewis CE, Liu S, Mackey RH, Robinson J, Rosal MC, Snetselaar L, Valoski A, Kuller LH. Severe obesity, heart disease, and death among white, African American, and Hispanic postmenopausal women. Obesity (Silver Spring). 2014 Mar;22(3):801-10. doi: 10.1002/oby.20224. Epub 2014 Feb 3
ethnic groups, extreme obesity, class III obesity, excess weight, mortality, morbidity, cardiovascular disease, women’s healthBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/24493096https://www.whi.org/researchers/bibliography/Manuscripts/ms432.pdf
To compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI ≥ 40), and examine heterogeneity in weight-related CHD risk.Among 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF).Mortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for.Severe obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity.
Publication
433
Baseline serum estradiol and fracture reduction during treatment with hormone therapy: The Women's Health Initiative randomized trialJane Cauley
Cauley JA, Lacroix AZ, Robbins JA, Larson J, Wallace R, Wactawski-Wende J, Chen Z, Bauer DC, Cummings SR, Jackson R. Baseline serum estradiol and fracture reduction during treatment with hormone therapy: The Women's Health Initiative randomized trial. Osteoporos Int. 2010 Jan;21(1):167-77. Epub 2009 May 13
fracture, hormone therapy, osteoporosis, mechanisms, bone turnover, estradiol, sex steroid hormone genesClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19436934https://www.whi.org/researchers/bibliography/Manuscripts/ms433.pdf
W9
The purpose of the study was to test the hypothesis that the reduction in fractures with hormone therapy (HT) is greater in women with lower estradiol levels.We conducted a nested case-control study within the Women's Health Initiative HT Trials. The sample included 231 hip fracture case-control pairs and a random sample of 519 all fracture case-control pairs. Cases and controls were matched for age, ethnicity, randomization date, fracture history, and hysterectomy status. Hormones were measured prior to randomization. Incident cases of fracture were identified over an average follow-up of 6.53 years.There was no evidence that the effect of HT on fracture differed by baseline estradiol (E2) or sex hormone binding globulin (SHBG). Across all quartiles of E2 and SHBG, women randomized to HT had about a 50% lower risk of fracture, including hip fracture, compared to placebo.The effect of HT on fracture reduction is independent of estradiol and SHBG levels.
Approved Proposal
434
Effect of the components of physical activity on cardiovascular outcomes in the Women’s Health Initiative Observational StudyGanesh Asaithamb
physical activity, mortality, coronary heart disease, cardiovascular disease, strokeObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms434pv2.pdf
Publication
436
Health characteristics of postmenopausal women with breast implantsPeter Rubin
Rubin JP, Landfair AS, Shestak K, Lane D, Valoski A, Chang Y, Tindle HA, Kuller LH. Health characteristics of postmenopausal women with breast implants. Plast Reconstr Surg. 2010 Mar;125(3):799-810
breast augmentation, health risks, quality of life, body image, psychological well-beingBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/20195108https://www.whi.org/researchers/bibliography/Manuscripts/ms436.pdf
Long-term health characteristics and quality of life in patients with breast implants are important issues in plastic surgery.The authors evaluated characteristics of women who had breast implant surgery in the Women's Health Initiative observational study between 1993 and 1998. Most women in this study cohort had breast implant surgery 20 or more years before recruitment into the study. The women who were in the study who had not undergone breast implant surgery served as the comparison group. There were 86,686 women in the study who did not have breast implant surgery and an absent history of breast cancer, and 1257 women who had breast implant surgery and no prior breast cancer.Total mortality rates were substantially lower among women with breast implants, as was the incidence of coronary heart disease. Women with breast implants in this study had a lower body mass index throughout adult life and were more physically active than control subjects. After adjustment for these variables, differences in total mortality were no longer statistically significant. Women who had breast implants reported overall poorer quality of life and emotional well-being. These differences were small, but statistically significant. Among women with breast implant surgery, 7 percent of deaths were due to suicide (n = 3) versus 0.4 percent (n = 20) in controls.Significant differences in health characteristics and quality-of-life measures are seen in a cohort of women with breast implants decades after implant surgery. Further longitudinal studies need to focus on both physical and psychological health among women undergoing breast implant surgery.
Publication
438
Walking speed and risk of incident ischemic stroke among postmenopausal womenRobert Kaplan
McGinn AP, Kaplan RC, Verghese J, Rosenbaum DM, Psaty BM, Baird AE, Lynch JK, Wolf PA, Kooperberg C, Larson JC, Wassertheil-Smoller S. Walking speed and risk of incident ischemic stroke among postmenopausal women. Stroke. 2008 Apr;39(4):1233-9. Epub 2008 Feb 21.
stroke, physical function, walking speedBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18292379https://www.whi.org/researchers/bibliography/Manuscripts/ms438.pdf
Walking speed is a simple, reliable, and valid measure of functional status that has been shown to be strongly correlated with age-related outcomes and may be an indicator of subclinical cerebrovascular disease. However, few studies have investigated the association of walking speed with risk of incident ischemic stroke.The present analyses included 13,048 postmenopausal women (mean age 65 years) from the Women's Health Initiative free of stroke at baseline, 264 of whom had incident ischemic strokes on follow-up. Cox proportional hazards regression was used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the relationship between performance on a timed walk and risk of incident ischemic stroke. Multivariate adjustment included age, race/ethnicity, body mass index, waist-hip ratio, depression, arthritis, hypertension, smoking, systolic blood pressure, treated diabetes, hormone use, NSAID use, aspirin use, self-reported general health, and history of coronary heart disease.Slower walking speed was a significant predictor of incident ischemic stroke. After multivariate adjustment, the hazard for incident ischemic stroke was increased for the slowest walking speed tertile compared to the fastest walking speed tertile (HR=1.69, 95% CI: 1.21, 2.36). Additional adjustment for other physical function variables (grip strength and chair stands) did not change the association significantly.Slow walking speed was found to be a strong predictor of increased risk of incident ischemic stroke among postmenopausal women independent of other established risk factors for stroke.
Publication
440
Monitoring and reporting of the Women’s Health Initiative randomized hormone therapy trialsGarnet Anderson
Anderson GL, Kooperberg C, Geller N, Rossouw JE, Pettinger M, Prentice RL. Monitoring and reporting of the Women’s Health Initiative randomized hormone therapy trials. Clin Trials. 2007;4(3):207-17.
Prevention trials, data monitoring, multiple testing, hormone therapy, women’s Health InitiativeClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17715246https://www.whi.org/researchers/bibliography/Manuscripts/ms440.pdf
The Women's Health Initiative (WHI) randomized trial of estrogen plus progestin (E + P) was terminated early based on an assessment of harms exceeding benefits for disease prevention. The results contravened prevailing wisdom and a large body of literature regarding benefits of menopausal hormone therapy. The results and their interpretation have been the subject of considerable debate.To describe the process of developing a trial monitoring plan, the key interim and final data, and to explain the choice of statistical methods used in trial monitoring and reporting.A formalized monitoring plan was developed using statistical methods that acknowledged protocol-defined design and analysis plans, input of monitoring board members especially regarding the role of various study outcomes, and multiple comparisons. Major early departures from design assumptions concerning treatment effects indicated a need for additional flexibility in safety monitoring. When the trials were stopped early, questions arose as to how closely the statistical methods in published reports should correspond to those defined by protocol or used in monitoring.were selected to provide a simple and transparent summary of the primary results, with a cautious interpretation promoted by acknowledgement of multiple testing.Developing a formal trial monitoring plan with a view towards influencing clinical practice is useful for creating consensus among DSMB members regarding the evidence that would justify stopping a trial and the framework to be used to address statistical complexities. Departures from design assumptions typically occur. These reinforce the role of the DSMB in exercising their judgment, and the judicious adaptation of these statistical guidelines in monitoring and reporting trials. In communicating the results in such circumstances, priority should be given to presenting as fair, accurate and transparent a view of the data and findings as current methods and technology allow.
Publication
441
Calcium plus the risk of postmenopausal weight gainBette Caan
Caan B, Neuhouser M, Aragaki A, Lewis CB, Jackson R, LeBoff MS, Margolis KL, Powell L, Uwaifo G, Whitlock E, Wylie-Rosett J, LaCroix A. Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain. Arch Intern Med. 2007 May 14;167(9):893-902.
Obesity, calcium, 25-hydroxyvitamin D, 1, 25-dihydroxyvitamin D, clinical trailsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17502530https://www.whi.org/researchers/bibliography/Manuscripts/ms441.pdf
Obesity in the United States has increased significantly during the past several decades. The role of calcium in the maintenance of a healthy body weight remains controversial.A randomized, double-blinded, placebo-controlled trial was performed with 36 282 postmenopausal women, aged 50 to 79 years, who were already enrolled in the dietary modification and/or hormone therapy arms of the Women's Health Initiative clinical trial. Women were randomized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol (vitamin D) or placebo daily. Change in body weight was ascertained annually for an average of 7 years.Women receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change (mean difference, -0.13 kg; 95% confidence interval, -0.21 to -0.05; P = .001). After 3 years of follow-up, women with daily calcium intakes less than 1200 mg at baseline who were randomized to supplements were 11% less likely to experience small weight gains (1-3 kg) and 11% less likely to gain more moderate amounts of weight (>3 kg) (P for interaction for baseline calcium intake = .008).Calcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain, which was observed primarily in women who reported inadequate calcium intakes.clinicaltrials.gov Identifier: NCT00000611.
Publication
442
Test-retest reliability of the Women’s Health Initiative Physical Activity QuestionnaireAnne-Marie Meyer
Meyer AM, Evenson KR, Morimoto L, Siscovick D, White E. Test-retest reliability of the Women's Health Initiative Physical Activity Questionnaire. Med Sci Sports Exerc. 2009 Mar;41(3):530-8. Epub 2009 Feb 6
physical activity, questionnaire, reliability, race/ethnicityObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19204598https://www.whi.org/researchers/bibliography/Manuscripts/ms442.pdf
W2
Few physical activity (PA) questionnaires were designed to measure the lifestyles and activities of women. We sought to examine the test-retest reliability of a PA questionnaire used in the Women's Health Initiative (WHI) study. Differences in reliability were also explored by important covariates.Participants (n = 1092) were postmenopausal women aged 50-79 yr, randomly selected from the baseline sample of participants in the WHI Observational Study. The WHI PA questionnaire collects usual frequency, duration, and pace of recreational walking, frequency, and duration of other recreational activities or exercises (mild, moderate, and strenuous), household, and yard activities. Approximately half of the women (n = 569) repeated questions on recreational PA, the other half (n = 523) repeated questions related to household and yard activities (mean 3 months apart). Test-retest reliability was assessed with kappa and intraclass correlation coefficients (ICC 1,1).Overall, questions on recreational walking, moderate recreational PA, and strenuous recreational PA had higher test-retest reliability (weighted kappa range = 0.50-0.60) than questions on mild recreational PA (weighted kappa range = 0.35-0.50). The ICC 1,1 for moderate to strenuous recreational PA was 0.77 (95% confidence interval [CI] = 0.73-0.80), and the total recreational PA was 0.76 (95% CI = 0.71-0.79). Substantial reliability was observed for the summary measures of yard activities (ICC 1,1 = 0.71; 95% CI = 0.66-0.75) and household activities (ICC 1,1 = 0.60, 95% CI = 0.55-0.66). No meaningful differences were observed by race/ethnicity, age, time between test and retest, and amount of reported PA.The WHI PA questionnaire demonstrated moderate to substantial test-retest reliability in a diverse sample of postmenopausal women.
Approved Proposal
443
Statin use and lung cancer risk in non-smoking postmenopausal womenNicolas Schlecht
statins, lung neoplasms, cancer incidence, risk, epidemiology, cohort studyObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms443p.pdf
Publication
444
Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women's Health InitiativeSuzen Moeller
Moeller SM, Voland R, Tinker L, Blodi BA, Klein ML, Gehrs KM, Johnson EJ, Snodderly DM, Wallace RB, Chappell RJ, Parekh N, Ritenbaugh C, Mares JA; for the CAREDS Study Group. Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women's Health Initiative. Arch Ophthalmol. 2008 Mar;126(3):354-364.
lutein, zeaxanthin, carotenoids, age-related nuclear cataract, lens opacities, serum, dietObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18332316https://www.whi.org/researchers/bibliography/Manuscripts/ms444.pdf
AS105
To evaluate associations between nuclear cataract (determined from slitlamp photographs between May 2001 and January 2004) and lutein and zeaxanthin in the diet and serum in patients between 1994 and 1998 and macula between 2001 and 2004.A total of 1802 women aged 50 to 79 years in Iowa, Wisconsin, and Oregon with intakes of lutein and zeaxanthin above the 78th (high) and below the 28th (low) percentiles in the Women's Health Initiative Observational Study (1994-1998) were recruited 4 to 7 years later (2001-2004) into the Carotenoids in Age-Related Eye Disease Study.Women in the group with high dietary levels of lutein and zeaxanthin had a 23% lower prevalence of nuclear cataract (age-adjusted odds ratio, 0.77; 95% confidence interval, 0.62-0.96) compared with those with low levels. Multivariable adjustment slightly attenuated the association (odds ratio, 0.81; 95% confidence interval, 0.65-1.01). Women in the highest quintile category of diet or serum levels of lutein and zeaxanthin as compared with those in the lowest quintile category were 32% less likely to have nuclear cataract (multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.97; P for trend = .04; and multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P for trend = .01, respectively). Cross-sectional associations with macular pigment density were inverse but not statistically significant.Diets rich in lutein and zeaxanthin are moderately associated with decreased prevalence of nuclear cataract in older women. However, other protective aspects of such diets may in part explain these relationships.
Publication
445
Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary eventsPaul Bray
Bray PF, Larson JC, LaCroix AZ, Manson J, Limacher MC, Rossouw JE, Lasser NL, Lawson WE, Stefanick ML, Langer RD, Margolis KL; Women's Health Initiative Investigators. Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events. Am J Cardiol. 2008 Jun 1;101(11):1599-1605. Epub 2008 Apr 2.
hormone therapy, cardiovascular disease, biomarkers, triglyceride, genesBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18489937https://www.whi.org/researchers/bibliography/Manuscripts/ms445.pdf
W6
Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio <2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio > or =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio <2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio <2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP.
Approved Proposal
446
Hormone exposure and risk of Parkinson’s disease among women with natural menopauseRachel Saunders-Pullman
observational study, estrogen exposure, Parkinson’s Disease, Parkinson’s disease, estrogen, progesterone, caffeine, smokingObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms446p.pdf
Publication
447
Low-fat dietary pattern and risk of cardiovascular disease: The Women’s Health Initiative Randomized Controlled Dietary Modification TrialBarbara Howard
Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil-Smoller S, Kuller LH, LaCroix AZ, Langer RD, Lasser NL, Lewis CE, Limacher MC, Margolis KL, Mysiw WJ, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Schatz IJ, Snetselaar LG, Stevens VJ, Tinker LF, Trevisan M, Vitolins MZ, Anderson GL, Assaf AR, Bassford T, Beresford SA, Black HR, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Granek I, Greenland P, Hays J, Heber D, Heiss G, Hendrix SL, Hubbell FA, Johnson KC, Kotchen JM. Low-fat dietary pattern and risk of cardiovascular disease: The Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):655-66
low-fat dietary pattern, cardiovascular disease, randomized controlled trialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16467234https://www.whi.org/researchers/bibliography/Manuscripts/ms447.pdf
W1
Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19,541 [40%]) or comparison group (29,294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.ClinicalTrials.gov Identifier: NCT00000611.
Publication
448
Low-fat dietary pattern and risk of invasive breast cancer: The Women’s Health Initiative Randomized Controlled Dietary Modification TrialRoss Prentice
Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, Margolis KL, Limacher MC, Manson JE, Parker LM, Paskett E, Phillips L, Robbins J, Rossouw JE, Sarto GE, Shikany JM, Stefanick ML, Thomson CA, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Wassertheil-Smoller S, Whitlock E, Yano K, Adams-Campbell L, Anderson GL, Assaf AR, Beresford SA, Black HR, Brunner RL, Brzyski RG, Ford L, Gass M, Hays J, Heber D, Heiss G, Hendrix SL, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Kotchen JM, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Henderson MM. Low-fat dietary pattern and risk of invasive breast cancer: The Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):629-42.
low-fat dietary pattern, breast cancer, randomized controlled trialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16467232https://www.whi.org/researchers/bibliography/Manuscripts/ms448.pdf
W1, W33
The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Invasive breast cancer incidence.Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.ClinicalTrials.gov Identifier: NCT00000611.
Publication
449
Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative randomized controlled dietary modification trialShirley Beresford
Beresford SA, Johnson KC, Ritenbaugh C, Lasser NL, Snetselaar LG, Black HR, Anderson GL, Assaf AR, Bassford T, Bowen D, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Harrigan RC, Hays J, Heber D, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Kotchen JM, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lewis CE, Manson JE, Margolis KL, Mossavar-Rahmani Y, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Stefanick ML, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Whitlock E. Low-fat dietary pattern and risk of colorectal cancer: The Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):643-54
low-fat dietary pattern, colorectal cancer, randomized controlled trialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16467233https://www.whi.org/researchers/bibliography/Manuscripts/ms449.pdf
W1
Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.Invasive colorectal cancer incidence.A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.ClinicalTrials.gov Identifier: NCT00000611.
Publication
450
Calcium plus vitamin D supplementation and the risk for fracturesRebecca Jackson
Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O'Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D, Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83.
calcium, vitamin D, fracturesClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16481635https://www.whi.org/researchers/bibliography/Manuscripts/ms450.pdf
W15
The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers.Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels.Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).
Publication
451
Calcium plus vitamin D supplementation and the risk of colorectal cancerJean Wactawski-Wende
Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE, Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med. 2006 Feb 16;354(7):684-96.
calcium, vitamin D, colorectal cancerClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16481636https://www.whi.org/researchers/bibliography/Manuscripts/ms451.pdf
W15
Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study.The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).
Publication
452
Macular pigment density and age-related maculopathy in the Carotenoids in Age-Related Eye Disease Study. An ancillary study of the Women's Health InitiativeTara LaRowe
Larowe TL, Mares JA, Snodderly DM, Klein ML, Wooten BR, Chappell R; CAREDS Macular Pigment Study Group. Macular pigment density and age-related maculopathy in the Carotenoids in Age-Related Eye Disease Study. An ancillary study of the Women's Health Initiative. Ophthalmology. 2008 May;115(5):876-883.e1. Epub 2007 Sep 14.
lutein, zeaxanthin, carotenoids, dietary intake, smoking, alcohol, body fatClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17868874https://www.whi.org/researchers/bibliography/Manuscripts/ms452.pdf
AS105
To examine the association between intermediate age-related macular degeneration (AMD) and the optical density of macular pigment (MPOD), which is composed of lutein and zeaxanthin from the diet.Cross-sectional cohort study.We included 1698 of 2005 women ages 54 to 86 years and participating in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative.The MPOD was measured noninvasively by heterochromatic flicker photometry. Fundus photographs were taken to document prevalent AMD.Intermediate AMD (n = 305) and two subtypes-large drusen (n = 233) and pigmentary abnormalities (n = 157).After adjusting for covariates, the odds ratio (OR) and 95% confidence interval (CI) for AMD among women in quintile (Q) 5 (n = 339) versus 1 (n = 340) for MPOD was 1.4 (0.9, 2.1). However, after excluding women with possible unstable diets and recent supplement use due to chronic disease history, associations reversed (OR Q2-5 vs. 1, 0.8; 95% CI, 0.5-1.2), but remained nonsignificant. Associations also differed between middle-aged (54-69 years) and older (> or =70 years) women (P-interaction = 0.09), but less so, after excluding women who were likely to have unstable diets: adjusted ORs (95% CI) were 0.5 (0.3-1.0; P = 0.08) for intermediate AMD among middle-aged women (n = 516) with MPOD in Q2 to Q5 versus 1 and 1.0 (0.5-2.0; P = 0.90) for older women (n = 422).The MPOD is not cross-sectionally associated with AMD. The inconsistency of relationships across age groups and in subgroups of women who are likely to have more stable diets suggests that cross-sectional associations may be biased and highlights the need to study these relationships prospectively.
Publication
453
Excess weight and physical health-related quality of life in postmenopausal women of diverse racial/ethnic backgroundsCheryl Lynch
Lynch CP, McTigue KM, Bost JE, Tinker LF, Vitolins M, Adams-Campbell L, Sarto GE, Hays-Grudo J, Manson JE, Kuller LH. Excess Weight and Physical Health-Related Quality of Life in Postmenopausal Women of Diverse Racial/Ethnic Backgrounds. J Womens Health (Larchmt). 2010 Aug;19(8):1449-58. doi: 10.1089/jwh.2009.1652. Epub 2010 Jul 14.
obesity, QOL, womenBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/20629574https://www.whi.org/researchers/bibliography/Manuscripts/ms453.pdf
Studies of weight and health-related quality of life (HRQOL) generally focus on white populations. This analysis examines the association between clinical weight categories and physical HRQOL in five racial/ethnic groups of older women and determines the extent to which emotional/psychological (social support, caregiver burden) and physical health (diabetes, osteoarthritis) factors modify this relationship.The cross-sectional analysis, completed in 2007, used baseline data from postmenopausal women enrolled in the Women's Health Initiative (WHI) during the 5-year recruitment period (1993-1998).Of 161,393 women, 83% were non-Hispanic white, 9% were African American, 4% were Hispanic/Latina, 3% were Asian/Pacific Islander, and <1% were American Indian/Alaska Native. Obesity (body mass index [BMI] > or =30 kg/m(2)) was most common in non-Asian minority groups. Regression modeling showed higher odds of poor physical HRQOL with increasing weight category in all groups. In the total sample, these odds were at least 6 times as high in women with class 3 obesity as in women of normal weight and were only mildly attenuated after the analysis adjusted for emotional/psychological factors. Further adjustment for physical health factors made odds ratio (OR) estimates drop from 2.36 to 1.59 for class 1 obesity and from 6.96 to 3.71 for class 3 obesity. This pattern generally persisted within each racial/ethnic group.Heavier weight negatively affects physical HRQOL in postmenopausal women across diverse racial/ethnic backgrounds. Weight-relevant physical health factors have a greater impact on this weight-HRQOL association than do emotional/psychological factors.
Publication
456
Dual-energy X-ray absorptiometry is a valid tool for assessing skeletal muscle mass in older womenZhao Chen
Chen Z, Wang Z, Lohman T, Heymsfield SB, Outwater E, Nicholas JS, Bassford T, LaCroix A, Sherrill D, Punyanitya M, Wu G, Going S. Dual-energy X-ray absorptiometry is a valid tool for assessing skeletal muscle mass in older women. J Nutr. 2007 Dec;137(12):2775-80.
skeletal muscle mass, DXA, SMM, muscle massBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18029498https://www.whi.org/researchers/bibliography/Manuscripts/ms456.pdf
AS153
Assessing skeletal muscle mass (SMM) is critical in studying and detecting sarcopenia. Direct measurements by MRI or computerized tomography are expensive or high in radiation exposure. Dual-energy X-ray absorptiometry (DXA) is promising for body composition assessments, but the validity of DXA for predicting SMM in the elderly is still under investigation. The objective of this study was to assess the relationship between DXA-derived measurements of lean soft tissue mass (LSTM) and SMM in older women. Study participants were postmenopausal women (n = 101) recruited in southern Arizona. Total and regional body composition was measured using MRI and DXA (QDR4500w). The participants' mean age was 70.7 +/- 6.4 y and their mean BMI was 27.4 +/- 5.1 kg/m2. DXA-derived LSTM was highly correlated with MRI-derived SMM for the whole body (r = 0.94; P < 0.001) and leg region (r = 0.91; P < 0.001). In multivariate models, adjusting for age and DXA-derived percent fat slightly increased the amount of variance in SMM that can be explained by the DXA-derived LSTM assessments for the leg region but not for the total body. In conclusion, although the relationships between DXA measures and MRI-derived SMM vary by region of interest, the overall prediction of SMM by DXA is excellent. We conclude that DXA is a reliable method for cross-sectional assessments of SMM in older women.
Publication
457
Hypertension and obesity and the risk of kidney cancer in 2 large cohorts of US men and womenLewis Kuller
Sanfilippo K, McTigue K, Fidler CJ, Neaton JD, Chang Y, Fried LF, Liu S, Kuller LH. Hypertension and obesity and the risk of kidney cancer in 2 large cohorts of US men and women. Hypertension. 2014;published online before print March 17 2014, doi:10.1161/HYPERTENSIONAHA.113.02953
hypertension, kidney cancerObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/24637660https://www.whi.org/researchers/bibliography/Manuscripts/Ms457.pdf
Kidney cancer incidence is increasing globally. Reasons for this rise are unclear but could relate to obesity and hypertension. We analyzed longitudinal relationships between hypertension and obesity and kidney cancer incidence in 156 774 participants of the Women's Health Initiative clinical trials and observational studies over 10.8 years. In addition, we examined the effect of blood pressure (BP) on kidney cancer deaths for over 25 years among the 353 340 men screened for the Multiple Risk Factor Intervention Trial (MRFIT). In the Women's Health Initiative, systolic BP (SBP) was categorized in 6 groups from <120 to >160 mm Hg, and body mass index was categorized using standard criteria. In age-adjusted analyses, kidney cancer risk increased across SBP categories (P value for trend <0.0001) and body mass index categories (P value for trend <0.0001). In adjusted Cox proportional hazards models, both SBP levels and body mass index were predictors of kidney cancer. In the MRFIT sample, there were 906 deaths after an average of 25 years of follow-up attributed to kidney cancer among the 353 340 participants aged 35 to 57 years at screening. The risk of death from kidney cancer increased in a dose-response fashion with increasing SBP (hazard ratio, 1.87 for SBP>160 versus <120 mm Hg; 95% confidence interval, 1.38-2.53). Risk was increased among cigarette smokers. Further research is needed to determine the pathophysiologic basis of relationships between both higher BP and the risk of kidney cancer, and whether specific drug therapies for hypertension can reduce kidney cancer risk.
Publication
458
Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health InitiativeKatherine Reeves
Reeves KW, Carter GC, Rodabough RJ, Lane D, McNeeley SG, Stefanick ML, Paskett ED. Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative. Gynecol Oncol. 2011 May 1;121(2):376-82. doi: 10.1016/j.ygyno.2011.01.027. Epub 2011 Feb 15.
BMI, endometrial cancer, stageBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/21324514https://www.whi.org/researchers/bibliography/Manuscripts/ms458.pdf
Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer.We studied 86937 postmenopausal women enrolled in the Women's Health Initiative. Height, weight, and waist and hip circumference were measured at baseline. Endometrial cancer cases were adjudicated by trained physicians and pathology reports were used to determine stage and grade. Cox proportional hazards models generated hazard ratios (HR) for associations between BMI and WHR and risk of endometrial cancer. Logistic regression was used to evaluate associations between BMI and WHR and disease stage and grade.During a mean 7.8 (standard deviation 1.6) years of follow-up, 806 women were diagnosed with endometrial cancer. Although incidence was higher among Whites, stage and grade were similar between Whites and Blacks. Elevated BMI (HR 1.76, 95% confidence interval [CI] 1.41-2.19) and WHR (HR 1.33, 95% CI 1.04-1.70) increased endometrial cancer risk when comparing women in the highest and lowest categories. No associations were observed between BMI or WHR and disease stage or grade.Obesity increases endometrial cancer risk independent of other factors but is not associated with stage or grade of disease. These findings support and validate previous reports. Future research should evaluate the impact of obesity on racial disparities in endometrial cancer survival.
Publication
459
A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancerMarc Gunter
Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Manson JE, Li J, Harris TG, Rohan TE, Xue X, Ho GY, Einstein MH, Kaplan RC, Burk RD, Wylie-Rosett J, Pollak MN, Anderson G, Howard BV, Strickler HD. A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):921-9.
Insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) estradiol, endometrial cancer, hormone replacement therapy, case-cohort design.Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18398032https://www.whi.org/researchers/bibliography/Manuscripts/ms459.pdf
AS129
Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HR(q4-q1)), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HR(q4-q1), 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HR(q4-q1), 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data.
Publication
460
Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal womenMarc Gunter
Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Howard BV, Wylie-Rosett J, Anderson GL, Ho GY, Kaplan RC, Li J, Xue X, Harris TG, Burk RD, Strickler HD. Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal women. Cancer Res. 2008 Jan 1;68(1):329-37.
Insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), estradiol, colorectal cancer, case-cohort design.Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18172327https://www.whi.org/researchers/bibliography/Manuscripts/ms460.pdf
AS129
Obesity is a risk factor for colorectal cancer, and hyperinsulinemia, a common condition in obese patients, may underlie this relationship. Insulin, in addition to its metabolic effects, has promitotic and antiapoptotic activity that may be tumorigenic. Insulin-like growth factor (IGF)-I, a related hormone, shares sequence homology with insulin, and has even stronger mitogenic effects. However, few prospective colorectal cancer studies directly measured fasting insulin, and none evaluated free IGF-I, or endogenous estradiol, a potential cofactor in postmenopausal women. Therefore, we conducted a case-cohort investigation of colorectal cancer among nondiabetic subjects enrolled in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. Fasting baseline serum specimens from all incident colorectal cancer cases (n = 438) and a random subcohort (n = 816) of Women's Health Initiative Observational Study subjects were tested for insulin, glucose, total IGF-I, free IGF-I, IGF binding protein-3, and estradiol. Comparing extreme quartiles, insulin [hazard ratio (HR)(q4-q1), 1.73; 95% confidence interval (CI), 1.16-2.57; P(trend) = 0.005], waist circumference (HR(q4-q1), 1.82; 95% CI, 1.22-2.70; P(trend) = 0.001), and free IGF-I (HR(q4-q1), 1.35; 95% CI, 0.92-1.98; P(trend) = 0.05) were each associated with colorectal cancer incidence in multivariate models. However, these associations each became nonsignificant when adjusted for one another. Endogenous estradiol levels, in contrast, were positively associated with risk of colorectal cancer (HR comparing high versus low levels, 1.53; 95% CI, 1.05-2.22), even after control for insulin, free IGF-I, and waist circumference. These data suggest the existence of at least two independent biological pathways that are related to colorectal cancer: one that involves endogenous estradiol, and a second pathway broadly associated with obesity, hyperinsulinemia, and free IGF-I.
Publication
461
Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal womenMarc Gunter
Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE, Li J, Ho GY, Xue X, Anderson GL, Kaplan RC, Harris TG, Howard BV, Wylie-Rosett J, Burk RD, Strickler HD. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2009 Jan 7;101(1):48-60. Epub 2008 Dec 30.
Insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) estradiol, breast cancer, hormone replacement therapy, case-cohort design.Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19116382https://www.whi.org/researchers/bibliography/Manuscripts/ms461.pdf
AS129
The positive association between obesity and postmenopausal breast cancer has been attributed, in part, to the fact that estrogen, a risk factor for breast cancer, is synthesized in adipose tissue. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed associations between circulating levels of insulin and/or insulin-like growth factor (IGF)-I, a related hormone, and the risk of breast cancer independent of estrogen level.We conducted a case-cohort study of incident breast cancer among nondiabetic women who were enrolled in the Women's Health Initiative Observational Study (WHI-OS), a prospective cohort of 93,676 postmenopausal women. Fasting serum samples obtained at study entry from 835 incident breast cancer case subjects and from a subcohort of 816 randomly chosen WHI-OS subjects were tested for levels of insulin, glucose, total IGF-I, free IGF-I, insulin-like growth factor binding protein-3, and estradiol. Multivariable Cox proportional hazards models were used to estimate associations between levels of the serologic factors and baseline characteristics (including body mass index [BMI]) and the risk of breast cancer. All statistical tests were two-sided. Results Insulin levels were positively associated with the risk of breast cancer (hazard ratio [HR] for highest vs lowest quartile of insulin level = 1.46, 95% confidence interval [CI] = 1.00 to 2.13, P(trend) = .02); however, the association with insulin level varied by hormone therapy (HT) use (P(interaction) = .01). In a model that controlled for multiple breast cancer risk factors including estradiol, insulin level was associated with breast cancer only among nonusers of HT (HR for highest vs lowest quartile of insulin level = 2.40, 95% CI = 1.30 to 4.41, P(trend) < .001). Obesity (BMI >or=30 kg/m(2)) was also associated with the risk of breast cancer among nonusers of HT (HR for BMI >or=30 kg/m(2) vs 18.5 to <25 kg/m(2) = 2.12, 95% CI = 1.26 to 3.58, P(trend) = .003); however, this association was attenuated by adjustment for insulin (P(trend) = .40).These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship.
Publication
462
Estrogen receptor polymorphisms and the vascular effects of hormone therapyJacques Rossouw
Rossouw J, Bray P, Liu J, Kooperberg C, Hsia J, Lewis C, Cushman M, Bonds D, Hendrix S, Papanicolaou G, Howard T, Herrington D. Estrogen Receptor Polymorphisms and the Vascular Effects of Hormone Therapy. Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):464-9. doi: 10.1161/ATVBAHA.110.215087. Epub 2010 Nov 24.
coronary heart disease, stroke, venous thromboembolism, estrogen, estrogen receptor, genetics, single nucleotide polymorphismsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/21106950https://www.whi.org/researchers/bibliography/Manuscripts/ms462.pdf
W11, W6
To test whether estrogen receptor polymorphisms modify the effects of postmenopausal hormone therapy on biomarkers and on risk of coronary heart disease events, stroke, or venous thromboembolism.The design was a nested case-control study in the Women's Health Initiative trials of postmenopausal hormone therapy. The study included all cases in the first 4 years: 359 cases of coronary heart disease, 248 of stroke, and 217 of venous thromboembolism. Six estrogen receptor-α polymorphisms and 1 estrogen receptor-β polymorphism were genotyped; 8 biomarkers known to be affected by hormone therapy were measured at baseline and 1 year after randomization. The polymorphisms were not associated with risk of vascular events and did not modify the increased risks of coronary heart disease, stroke, or venous thromboembolism due to hormone therapy. However, a reduced response of plasmin-antiplasmin to hormone therapy was noted for estrogen receptor-1 IVS1 (intron number 1)-354 (interaction P<0.0001, corrected for multiple comparisons P=0.014) and estrogen receptor-1 IVS1-1415 (interaction P<0.0001, corrected P=0.014).Estrogen receptor polymorphisms reduce the effect of postmenopausal hormone therapy on plasmin-antiplasmin, a marker of coagulation and fibrinolysis. However, screening for estrogen receptor polymorphisms to identify women at less risk of adverse cardiovascular outcomes is not likely to be useful in making decisions about hormone therapy treatment.
Approved Proposal
463
Glycemic load and risk of coronary heart disease in the Women’s Health Initiative observational studyJames Shikany
insulin resistance/hyperinsulinemia, inflammation, and thrombogenesis/impaired fibrinolysisObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms463p.pdf
AS111
Publication
464
Use of recovery biomarkers to calibrate nutrient consumption self-reports in the Women's Health InitiativeMarian Neuhouser
Neuhouser ML, Tinker L, Shaw PA, Schoeller D, Bingham SA, Van Horn L, Beresford SAA, Caan B, Thomson C, Satterfield S, Kuller L, Heiss G, Smit E, Sarto G, Ockene J, Stefanick ML, Assaf A, Runswick S, Prentice RL. Use of recovery biomarkers to calibrate nutrient consumption self-reports in the Women's Health Initiative. Am J Epidemiol. 2008 May 15;167(10):1247-59. Epub 2008 Mar 15.
biomarkers, energy intake, protein intake, doubly labeled water, epidemiologic methods, nutritional epidemiology, measurement errorClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18344516https://www.whi.org/researchers/bibliography/Manuscripts/ms464.pdf
W8
Underreporting of energy consumption by self-report is well-recognized, but previous studies using recovery biomarkers have not been sufficiently large to establish whether participant characteristics predict misreporting. In 2004-2005, 544 participants in the Women's Health Initiative Dietary Modification Trial completed a doubly labeled water protocol (energy biomarker), 24-hour urine collection (protein biomarker), and self-reports of diet (assessed by food frequency questionnaire (FFQ)), exercise, and lifestyle habits; 111 women repeated all procedures after 6 months. Using linear regression, the authors estimated associations of participant characteristics with misreporting, defined as the extent to which the log ratio (self-reported FFQ/nutritional biomarker) was less than zero. Intervention women in the trial underreported energy intake by 32% (vs. 27% in the comparison arm) and protein intake by 15% (vs. 10%). Younger women had more underreporting of energy (p = 0.02) and protein (p = 0.001), while increasing body mass index predicted increased underreporting of energy and overreporting of percentage of energy derived from protein (p = 0.001 and p = 0.004, respectively). Blacks and Hispanics underreported more than did Caucasians. Correlations of initial measures with repeat measures (n = 111) were 0.72, 0.70, 0.46, and 0.64 for biomarker energy, FFQ energy, biomarker protein, and FFQ protein, respectively. Recovery biomarker data were used in regression equations to calibrate self-reports; the potential application of these equations to disease risk modeling is presented. The authors confirm the existence of systematic bias in dietary self-reports and provide methods of correcting for measurement error.
Publication
466
Low-fat dietary pattern intervention and health-related quality of life: The Women's Health Initiative Randomized Controlled Dietary Modification TrialAnnlouise Assaf
Assaf AR, Beresford SA, Risica PM, Aragaki A, Brunner RL, Bowen DJ, Naughton M, Rosal MC, Snetselaar L, Wenger N. Low-fat dietary pattern intervention and health-related quality of life: The Women's Health Initiative Randomized Controlled Dietary Modification Trial. J Acad Nutr Diet. 2016 Feb;116(2):259-71. doi: 10.1016/j.jand.2015.07.016. Epub 2015 Sep 16
dietary modification, quality of life, depression, sleep qualityClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/26384466https://www.whi.org/researchers/bibliography/Manuscripts/ms466.pdf
Intensive dietary intervention programs may lead to benefits in vitality and other components of health quality. The Women's Health Initiative Dietary Modification (DM) intervention includes a large randomized controlled trial of an intensive intervention.To evaluate whether the intervention is associated with improved health-related quality of life (HRQoL) subscales, overall self-reported health, depression symptoms, cognitive functioning, and sleep quality.This randomized controlled trial was analyzed as intent to treat.Between 1993 and 1998, 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States. Eligibility included having fat intake at baseline ≥32% of total calories, and excluded women with any prior colorectal or breast cancer, recent other cancers, type 1 diabetes, or medical conditions with predicted survival <3 years.Goals were to reduce calories from fat to 20%, increase vegetables and fruit to 5+ servings, and increase grain servings to 6+ servings a day. During the first year, 18 group sessions were held, with quarterly sessions thereafter.The RAND 36-Item Health Survey was used to assess HRQoL at baseline, Year 1, and close-out (about 8 years postrandomization), and estimate differential HRQoL subscale change scores.Mean change in HRQoL scores (Year 1 minus baseline) were compared by randomization group using linear models.At 1 year, there was a differential change between intervention and comparison group of 1.7 units (95% CI 1.5, 2.0) in general health associated with the intervention. DM intervention improved physical functioning by 2.0 units (95% CI 1.7, 2.3), vitality by 1.9 units (95% CI 1.6, 2.2), and global quality of life by 0.09 units (95% CI 0.07, 0.12). With the exception of global quality of life, these effects were significantly modified by body mass index at baseline.DM intervention was associated with small, but significant improvements in three HRQoL subscales: general health, physical functioning, and vitality at 1 year follow-up, with the largest improvements seen in the women with the greatest baseline body mass index.
Publication
467
Low-fat, increased fruit, vegetable, and grain dietary pattern, fractures, and bone mineral density: the Women's Health Initiative Dietary Modification TrialAnne McTiernan
McTiernan A, Wactawski-Wende J, Wu L, Rodabough RJ, Watts NB, Tylavsky F, Freeman R, Hendrix S, Jackson R. Low-fat, increased fruit, vegetable, and grain dietary pattern, fractures, and bone mineral density: the Women’s Health Initiative Dietary Modification Trial. Am J Clin Nutr. 2009 Jun;89(6):1864-76. Epub 2009 Apr 29
osteopenia, osteoporosis, fractures, postmenopausal womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19403636https://www.whi.org/researchers/bibliography/Manuscripts/ms467.pdf
The effects of dietary changes on osteoporosis, low bone density, and frequent falls are unestablished.We assessed the effect of the Women's Health Initiative Dietary Modification low-fat and increased fruit, vegetable, and grain intervention on incident hip, total, and site-specific fractures and self-reported falls, and, in a subset, on bone mineral density (BMD).Postmenopausal women (n = 48,835) aged 50-79 y (18.6% of minority race-ethnicity) were randomly assigned to receive the Dietary Modification intervention (40%, n = 19,541) (daily goal: < or =20% of energy as fat, > or =5 servings of vegetables and fruit, and > or =6 servings of grains) or to a comparison group that received no dietary changes (60%; n = 29,294).After a mean 8.1 y of follow-up, 215 women in the intervention group and 285 women in the comparison group (annualized rate: 0.14% and 0.12%, respectively) experienced a hip fracture (hazard ratio: 1.12; 95% CI: 0.94, 1.34; P = 0.21). The intervention group (n = 5423; annualized rate: 3.44%) had a lower rate of reporting > or =2 falls than did the comparison group (n = 8695; annualized rate: 3.67%) (HR: 0.92; 95% CI: 0.89, 0.96; P < 0.01). There was a significant interaction according to hormone therapy use; those in the comparison group receiving hormone therapy had the lowest incidence of hip fracture. In a subset of 3951 women, hip BMD at years 3, 6, and 9 was 0.4-0.5% lower in the intervention group than in the comparison group (P = 0.003).A low-fat and increased fruit, vegetable, and grain diet intervention modestly reduced the risk of multiple falls and slightly lowered hip BMD but did not change the risk of osteoporotic fractures. This trial was registered at clinicaltrials.gov as NCT00000611.
Publication
468
Effect of calcium and vitamin D supplementation on blood pressure: the Women’s Health Initiative Randomized TrialKaren Margolis
Margolis KL, Ray RM, Van Horn L, Manson JE, Allison MA, Black HR, Beresford SA, Connelly SA, Curb JD, Grimm RH Jr, Kotchen TA, Kuller LH, Wassertheil-Smoller S, Thomson CA, Torner JC; Women's Health Initiative Investigators. Effect of calcium and vitamin D supplementation on blood pressure: the Women's Health Initiative Randomized Trial. Hypertension. 2008 Nov;52(5):847-55. doi: 10.1161/HYPERTENSIONAHA.108.114991. Epub 2008 Sep 29
Calcium supplementation, 25-hydroxyvitamin D, 1, 25-dihydroxyvitamin D, blood pressure, hypertension, clinical trialsClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18824662https://www.whi.org/researchers/bibliography/Manuscripts/ms468.pdf
Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women. The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: -0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: -0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI: 0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up.
Publication
469
Low-fat dietary pattern and cancer incidence in the Women's Health Initiative Dietary Modification Randomized Controlled TrialRoss Prentice
Prentice RL, Thomson CA, Caan B, Hubbell FA, Anderson GL, Beresford SAA, Pettinger M, Lane DS, Lessin L, Yasmeen S, Singh B, Khandekar J, Shikany JM, Satterfield S, Chlebowski RT. Low-fat dietary pattern and cancer incidence in the Women's Health Initiative Dietary Modification Randomized Controlled Trial. J Natl Cancer Inst. 2007 Oct 17;99(20):1534-43. Epub 2007 Oct 9
Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17925539https://www.whi.org/researchers/bibliography/Manuscripts/ms469.pdf
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The Women's Health Initiative Dietary Modification (DM) Randomized Controlled Trial evaluated the effects of a low-fat dietary pattern on chronic disease incidence, with breast cancer and colorectal cancer as primary outcomes. The trial protocol also listed ovarian cancer and endometrial cancer as outcomes that may be favorably affected by the intervention.A total of 48,835 postmenopausal women were randomly assigned during 1993-1998 to a DM intervention (n = 19,541) or comparison (usual diet; n = 29,294) group and followed up for an average of 8.1 years. The intervention goal was to reduce total fat intake to 20% of energy and to increase consumption of vegetables, fruits, and grains. Cancer outcomes were verified by pathology report review. We used weighted log-rank tests to compare incidence of invasive cancers of the ovary and endometrium, total invasive cancer, and invasive cancers at other sites between the groups. All statistical tests were two-sided.Ovarian cancer risk was lower in the intervention than in the comparison group (P = .03). Although the overall ovarian cancer hazard ratio (HR) was not statistically significantly less than 1.0, the hazard ratio decreased with increasing intervention duration (P(trend) = .01). For the first 4 years, the risk for ovarian cancer was similar in the intervention and control groups (0.52 cases per 1000 person-years in the intervention group versus 0.45 per 1000 person-years in the comparison group; HR = 1.16, 95% confidence interval [CI] = 0.73 to 1.84); over the next 4.1 years, the risk was lower in the intervention group (0.38 cases per 1000 person-years in the intervention group versus 0.64 per 1000 person-years in the comparison group; HR = 0.60, 95% CI = 0.38 to 0.96). Risk of cancer of the endometrium did not differ between the groups (P = .18). The estimated risk of total invasive cancer was slightly lower in the intervention group than in the control group (HR = 0.95, 95% CI = 0.89 to 1.01; P = .10).A low-fat dietary pattern may reduce the incidence of ovarian cancer among postmenopausal women.
Publication
470
25-Hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal womenRowan Chlebowski
Chlebowski RT, Johnson KC, Lane D, Pettinger M, Kooperberg CL, Wactawski-Wende J, Rohan T, O’Sullivan MJ, Yasmeen S, Hiatti RA, Shikany JM, Vitolins M, Khandekar J, and Hubbell FA. 25-Hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal women. Maturitas. 2011 Jan;68(1):73-8. doi: 10.1016/j.maturitas.2010.10.006. Epub 2010 Nov 18.
none providedClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/21093181https://www.whi.org/researchers/bibliography/Manuscripts/ms470.pdf
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Low 25-hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms.Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial.25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling.The 25(OH) D levels were commonly low with 53% having deficient (<50 nmol/L) and only 17% having sufficient (>72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R=0.29, p<0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P=0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile.Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials.
Publication
471
Calcium/vitamin D supplementation and cardiovascular eventsJudith Hsia
Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M, Women's Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation. 2007 Feb 20;115(7):846-54.
Clinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17309935https://www.whi.org/researchers/bibliography/Manuscripts/ms471.pdf
Individuals with vascular or valvular calcification are at increased risk for coronary events, but the relationship between calcium consumption and cardiovascular events is uncertain. We evaluated the risk of coronary and cerebrovascular events in the Women's Health Initiative randomized trial of calcium plus vitamin D supplementation.We randomized 36,282 postmenopausal women 50 to 79 years of age at 40 clinical sites to calcium carbonate 500 mg with vitamin D 200 IU twice daily or to placebo. Cardiovascular disease was a prespecified secondary efficacy outcome. During 7 years of follow-up, myocardial infarction or coronary heart disease death was confirmed for 499 women assigned to calcium/vitamin D and 475 women assigned to placebo (hazard ratio, 1.04; 95% confidence interval, 0.92 to 1.18). Stroke was confirmed among 362 women assigned to calcium/vitamin D and 377 assigned to placebo (hazard ratio, 0.95; 95% confidence interval, 0.82 to 1.10). In subgroup analyses, women with higher total calcium intake (diet plus supplements) at baseline were not at higher risk for coronary events (P=0.91 for interaction) or stroke (P=0.14 for interaction) if assigned to active calcium/vitamin D.Calcium/vitamin D supplementation neither increased nor decreased coronary or cerebrovascular risk in generally healthy postmenopausal women over a 7-year use period.
Publication
472
Calcium plus Vitamin D supplementation and mortality in postmenopausal women: The Women's Health Initiative Calcium–Vitamin D Randomized Controlled TrialAndrea LaCroix
LaCroix AZ, Kotchen J, Anderson G, Brzyski R, Cauley JA, Cummings SR, Gass M, Johnson KC, Ko M, Larson J, Manson JE, Stefanick ML, Wactawski-Wende J.  Calcium plus Vitamin D supplementation and mortality in postmenopausal women: The Women's Health Initiative Calcium–Vitamin D Randomized Controlled Trial. J Gerontol A Biol Sci Med Sci. 2009 May;64(5):559-67. Epub 2009 Feb 16
none providedClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19221190https://www.whi.org/researchers/bibliography/Manuscripts/ms472.pdf
Calcium and vitamin D (CaD) supplementation trials including the Women's Health Initiative (WHI) trial of CaD have shown nonsignificant reductions in total mortality. This report examines intervention effects on total and cause-specific mortality by age and adherence.The WHI CaD trial was a randomized, double-blind, placebo-controlled trial that enrolled 36,282 postmenopausal women aged 51-82 years from 40 U.S. clinical centers. Women were assigned to 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D(3) daily or placebo with average follow-up of 7.0 years.The hazard ratio (HR) for total mortality was 0.91 (95% confidence interval [CI], 0.83-1.01) with 744 deaths in women randomized to CaD versus 807 deaths in the placebo group. HRs were in the direction of reduced risk but nonsignificant for stroke and cancer mortality, but near unity for coronary heart disease and other causes of death. HRs for total mortality were 0.89 in the 29,942 women younger than 70 years (95% CI, 0.79-1.01) and 0.95 in the 6,340 women aged 70 and older (95% CI, 0.80-1.12; p value for age interaction = .10). No statistically significant interactions were observed for any baseline characteristics. Treatment effects did not vary significantly by season.In the WHI CaD trial, supplementation did not have a statistically significant effect on mortality rates but the findings support the possibility that these supplements may reduce mortality rates in postmenopausal women. These data can neither support nor refute recommendations for higher dose vitamin D supplementation to reduce cancer or total mortality.
Publication
473
Urinary tract stone occurrence in the Women's Health Initiative randomized clinical trial of calcium and vitamin D supplementsRobert Wallace
Wallace RB, Wactawski-Wende J, O'Sullivan MJ, Larson JC, Cochrane B, Gass M, and Masaki K. Urinary tract stone occurrence in the Women's Health Initiative randomized clinical trial of calcium and vitamin D supplements. Am J Clin Nutr. 2011 Jul;94(1):270-7. doi: 10.3945/ajcn.110.003350. Epub 2011 Apr 27.
none providedClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/21525191https://www.whi.org/researchers/bibliography/Manuscripts/ms473.pdf
The Women's Health Initiative (WHI) randomized clinical trial (RCT) of calcium plus vitamin D (CaD) supplements found a 17% excess in urinary tract stone incidence in the supplemented group. This study evaluated whether this risk is modified by participant characteristics.We examined the correlates of urinary tract stone occurrence in the CaD arm of the WHI trial.We analyzed an RCT involving 36,282 postmenopausal women aged 50-79 y from 40 WHI centers: 18,176 women received 500 mg calcium carbonate plus 200 IU vitamin D(3) twice daily (1000 mg and 400 IU daily, respectively), and 18,106 women received a matching placebo for an average of 7.0 y. The incidence of urinary tract stones was determined.The incidence of self-reported clinically diagnosed urinary tract stones was more common in the active CaD medication group than in the placebo group (hazard ratio: 1.17; 95% CI: 1.02, 1.34): 449 women in the CaD group and 381 women in the placebo group reported a stone during the trial. The rates of self-reported stones did not differ between various demographic, anthropomorphic, dietary, and other hypothesized risk factors according to randomization assignment. Neither the total calcium intake nor the use of calcium supplements at baseline was associated with the risk of stones. In sensitivity analyses that censored participants who were below 80% adherence, the findings were similar.Daily supplementation with CaD for 7 y was associated with an increase in the number of self-reported urinary tract stones. These findings have implications for CaD supplement use. This trial was registered with the WHI at clinicaltrials.gov as NCT00000611.
Publication
475
Calcium, vitamin D supplementation, and physical function in the Women's Health InitiativeRobert Brunner
Brunner RL, Cochrane B, Jackson RD, Larson J, Lewis C, Limacher M, Rosal M, Shumaker S, Wallace R; Women's Health Initiative Investigators. Calcium, Vitamin D Supplementation, and Physical Function in the Women's Health Initiative. J Am Diet Assoc. 2008 Sep;108(9):1472-9.
supplemented calcium/vitamin D; post-menopausal women; physical function; randomized controlled trialClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18755319https://www.whi.org/researchers/bibliography/Manuscripts/ms475.pdf
The Women's Health Initiative (WHI) randomized trial of calcium/vitamin D supplementation found reduced bone loss with active treatment compared to placebo. Now we examine whether the treatment affected self-reported physical functioning and objective measures of physical functioning.A randomized, double-blind, placebo-controlled trial of 1,000 mg calcium carbonate plus 400 IU vitamin D(3) per day or matching placebo pills.The study included 33,067 women (50 to 79 years old) at 40 US study centers.Physical functioning was assessed by questionnaire at enrollment in WHI, 1 year prior to calcium/vitamin D trial randomization and at study close-out (average follow-up 7.1 years). Objective physical performance and self-reported exercise measures were collected at WHI baseline (1 year prior to calcium/vitamin D enrollment) and 2 years and 4 years after calcium/vitamin D trial enrollment in a subsample (n=3,137).Calcium/vitamin D effects were tested in unadjusted and interaction linear models for each of the physical function measures. Covariates were baseline total calcium intake, fracture risk score, treatment arm in the hormone therapy and dietary modification trials (ie, active drug or placebo, low-fat diet intervention or usual diet, respectively) and age.Neither intention to treat nor high adherence analyses produced substantial effects of calcium/vitamin D compared to placebo on physical functioning or performance. The interaction analyses also did not result in differences because of calcium/vitamin D.As the first long-term randomized trial to examine the effectiveness of calcium and vitamin D in protecting against decline of physical functioning in older women, the results did not support benefit.
Publication
479
Homocysteine levels and risk of hip fracture in postmenopausal womenMeryl LeBoff
LeBoff MS, Narweker R, LaCroix A, Wu L, Jackson R, Lee J, Bauer DC, Cauley J, Kooperberg C, Lewis C, Thomas AM, Cummings S. Homocysteine levels and risk of hip fracture in postmenopausal women. J Clin Endocrinol Metab. 2009 Apr;94(4):1207-13. Epub 2009 Jan 27
homocysteine, hip, fracture, WHI, postmenopausalObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19174498https://www.whi.org/researchers/bibliography/Manuscripts/ms479.pdf
AS90
Recent studies suggest that high homocysteine levels are associated with an increased risk of fractures. Homocysteine levels are known to be influenced by vitamin B and folate supply or status, and poor renal function can result in higher levels independent of nutritional adequacy.The aim of the study was to determine the associations between fasting homocysteine levels and incident hip fractures, and the effects of other factors on hip fracture risk.We conducted a case-control study in the Women's Health Initiative Observational Study, a study of postmenopausal women (n = 93,676) recruited in the United States. We selected 400 incident cases of hip fracture and 400 controls matched on age, ethnicity, and blood draw date among women not on osteoporosis therapies. Outcome measures included physician-adjudicated, incident hip fractures. Baseline lifestyle and nutritional questionnaires were performed.The risk of hip fracture increased 1.38-fold [95% confidence interval (CI), 1.14, 1.66] for each sd increase in serum homocysteine level after adjustment for fracture risk factors. This association was not affected by adjustment for dietary folate, B6, or B12 intake, but it diminished after adjustment for cystatin-C level (odds ratio, 1.08; 95% CI, 0.66-1.79), a measure of renal function not affected by muscle mass. Among women in the highest quartile of homocysteine and cystatin-C compared to those without elevations in either biomarker, the risk of hip fracture was substantially elevated (odds ratio, 2.8; 95% CI, 1.61-4.87).This study indicates that high homocysteine levels are associated with an increased risk of hip fracture, which could be accounted for by poor renal function.
Publication
481
Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal womenJennifer Lee
Lee JS, Lacroix AZ, Wu L, Cauley JA, Jackson RD, Kooperberg C, Leboff MS, Robbins J, Lewis CE, Bauer DC, Cummings SR. Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women. J Clin Endocrinol Metab. 2008 May;93(5):1796-803. Epub 2008 Mar 11.
estradiol, testosterone, sex hormone binding globulin, hip fracture, sex hormonesObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18334588https://www.whi.org/researchers/bibliography/Manuscripts/ms481.pdf
AS90
Endogenous estradiol, testosterone, and SHBG may influence the risk of hip fracture.From the Women's Health Initiative Observational Study, 39,793 eligible postmenopausal women did not have a previous hip fracture and were not using estrogen or other bone-active therapies. Of these, 400 who had a first-time nonpathological hip fracture (median follow-up, 7 yr) were matched to 400 controls by age, ethnicity, and baseline blood draw date. Estradiol, testosterone, and SHBG were measured in banked baseline serum.Compared with women in the lowest tertiles, those with bioavailable testosterone in the highest tertile had a lower risk [odds ratio (OR) = 0.62; 95% confidence interval (CI) = 0.44-0.88]; those with bioavailable estradiol in the highest tertile had a lower risk (OR = 0.44; 95% CI = 0.29-0.66), and those with SHBG in the highest tertile had a higher risk (OR = 1.90; 95% CI = 1.31-2.74) of hip fracture. In models with all three hormones and potential confounders, high SHBG remained a strong independent risk factor (OR = 1.76; 95% CI = 1.12-2.78), high bioavailable testosterone remained protective (OR = 0.64; 95% CI = 0.40-1.00), but estradiol no longer was associated (OR = 0.72; 95% CI = 0.42-1.23).High serum SHBG is associated with an increased risk of subsequent hip fracture and high endogenous testosterone with a decreased risk, independent of each other, serum estradiol concentration, and other putative risk factors. But endogenous estradiol has no independent association with hip fracture.
Publication
482
Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohortsEva Schernhammer
Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ, Fuchs C. Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res. 2007 Jun 1;67(11):5553-60.
Folate, pancreatic cancer, epidemiology, prospective study, vitamin B6, vitamin B12, homocysteineObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17545639https://www.whi.org/researchers/bibliography/Manuscripts/ms482.pdf
AS146
Folate deficiency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation. Few studies have examined the influence of one-carbon nutrients on pancreatic cancer risk, although recent studies suggest a potential protective effect for one-carbon nutrients from food sources, but not from supplements. We conducted a prospective nested case-control study to examine plasma concentrations of folate, vitamin B6 [whose main circulating form is pyridoxal-5'-phosphate (PLP)], vitamin B12, and homocysteine in relationship to pancreatic cancer, using four large prospective cohorts. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. All statistical tests were two sided. Among 208 cases and 623 controls, we observed no association between folate, PLP, vitamin B12, or homocysteine and pancreatic cancer risk. Comparing the highest to lowest quartiles of plasma concentration, the ORs were 1.20 (95% CI, 0.76-1.91) for folate, 0.80 (95% CI, 0.51-1.25) for B6, 0.91 (95% CI, 0.57-1.46) for B12, and 1.43 (95% CI, 0.90-2.28) for homocysteine. In analyses restricted to nonusers of multivitamins, we observe a modest inverse trend between folate, PLP, and B12 and pancreatic cancer risk. In contrast, no such inverse associations were observed among study subjects who reported multivitamin supplement use. Among all participants, plasma levels of folate, B6, B12, and homocysteine were not associated with a significant reduction in the risk of pancreatic cancer. Among participants who obtain these factors exclusively through dietary sources, there may be an inverse relation between circulating folate, B6, and B12 and risk.
Publication
483
Prediagnostic plasma C-peptide and pancreatic cancer risk in men and womenDominique Michaud
Michaud DS, Wolpin B, Giovannucci E, Liu S, Cochrane B, Manson JE, Pollak MN, Ma J, Fuchs CS. Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women. Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2101-9. Epub 2007 Sep 28.
Insulin, C-peptide, pancreatic cancer, epidemiology, prospective study, insulin-like growth factor binding proteinsObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17905943https://www.whi.org/researchers/bibliography/Manuscripts/ms483.pdf
AS146
Hyperinsulinemia and insulin resistance have been proposed as underlying mechanisms for the increase in pancreatic cancer among long-standing diabetics and obese individuals. An association between serum insulin levels and pancreatic cancer risk was reported in a recent study, but the population was composed of heavy smokers and their findings may not be generalizable to nonsmokers.Pancreatic cancer cases and matched controls were obtained from four large-scale prospective cohorts to examine the association between prediagnostic plasma levels of C-peptide and insulin and pancreatic cancer. One hundred ninety-seven pancreatic cancer cases were diagnosed during a maximum of 20 years of follow-up, after excluding cases diagnosed within 2 years of blood collection or with baseline diabetes. We estimated OR and confidence intervals (CI) using conditional logistic regression with adjustment for pancreatic cancer risk factors.Prediagnostic plasma C-peptide was positively associated with pancreatic cancer risk (OR, 1.52; 95% CI, 0.87-2.64, highest compared with the lowest quartile, P(trend) = 0.005). The association was not modified by body mass index or physical activity but seemed to be slightly stronger among never smokers than ever smokers. Fasting C-peptide and insulin were not related to pancreatic cancer; however, we observed a strong linear association for nonfasting C-peptide and pancreatic cancer (OR, 4.24; 95% CI, 1.30-13.8, highest versus lowest quartile, P(trend) < 0.001).Based on our finding of a strong positive association with nonfasting C-peptide levels, we propose that insulin levels in the postprandial state may be the relevant exposure for pancreatic carcinogenesis; however, other studies will need to examine this possibility.
Publication
484
Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohortsBrian Wolpin
Wolpin BM, Michaud DS, Giovannucci EL, Schernhammer ES, Stampfer MJ, Manson JE, Cochrane BB, Rohan TE, Ma J, Pollak MN, Fuchs CS. Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts. Br J Cancer. 2007 Jul 2;97(1):98-104. Epub 2007 May 29.
Insulin-like growth factors, pancreatic cancer, epidemiology, prospective study, insulin-like growth factor binding proteinsObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17533398https://www.whi.org/researchers/bibliography/Manuscripts/ms484.pdf
AS146
Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity. The association of plasma IGF-I and IGF binding protein-3 (IGFBP-3) with pancreatic cancer risk has been investigated in two small studies, with conflicting results. We conducted a nested case-control study within four large, prospective cohorts to investigate whether prediagnostic plasma levels of IGF-I, IGF-II, and IGFBP-3 were associated with pancreatic cancer risk. Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression, with adjustment for other known pancreatic cancer risk factors. No association was observed between plasma levels of IGF-I, IGF-II, or IGFBP-3 and incident diagnosis of pancreatic cancer. Relative risks for the highest vs the lowest quartile of IGF-I, IGF-II, and IGFBP-3 were 0.94 (95% confidence interval (CI), 0.60-1.48), 0.96 (95% CI, 0.61-1.52), and 1.21 (95% CI, 0.75-1.92), respectively. The relative risk for the molar ratio of IGF-I and IGFBP-3, a surrogate measure for free IGF-I, was 0.84 (95% CI, 0.54-1.31). Additionally, no association was noted in stratified analyses or when requiring longer follow-up. In four prospective cohorts, we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I, IGF-II, or IGFBP-3.
Approved Proposal
485
Caffeine and risk of Parkinson’s disease in womenRachel Saunders-Pullman
Parkinson’s disease, caffeine, estrogenObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms485p.pdf
Publication
486
Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: The Women's Health Initiative Observational StudyYiquing Song
Song Y, Manson JE, Tinker L, Howard BV, Kuller LH, Nathan L, Rifai N, Liu S. Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women: The Women's Health Initiative Observational Study. Diabetes Care. 2007 Jul;30(7):1747-52. Epub 2007 Apr 27.
Type 2 diabetes mellitus (Type 2 DM), fasting insulin levels, glucose levels, insulin resistance, insulin secretion, the Homeostasis Model Assessment (HOMA)Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17468352https://www.whi.org/researchers/bibliography/Manuscripts/ms486.pdf
AS132
The homeostasis model assessment (HOMA), based on plasma levels of fasting glucose and insulin, has been widely validated and applied for quantifying insulin resistance and beta-cell function. However, prospective data regarding its relation to diabetes risk in ethnically diverse populations are limited.Among 82,069 women who were aged 50-79 years, free of cardiovascular disease or diabetes, and participating in the Women's Health Initiative Observational Study, we conducted a nested case-control study to prospectively examine the relations of HOMA of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) with diabetes risk. During a median follow-up period of 5.9 years, 1,584 diabetic patients were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood draw, and follow-up time.Baseline levels of fasting glucose, insulin, and HOMA-IR were each significantly higher among case compared with control subjects, while HOMA-B was lower (all P values <0.0001). After adjustment for matching factors and diabetes risk factors, all four markers were significantly associated with diabetes risk; the estimated relative risks per SD increment were 3.54 (95% CI 3.02-4.13) for fasting glucose, 2.25 (1.99-2.54) for fasting insulin, 3.40 (2.95-3.92) for HOMA-IR, and 0.57 (0.51-0.63) for HOMA-B. While no statistically significant multiplicative interactions were observed between these markers and ethnicity, the associations of both HOMA-IR and HOMA-B with diabetes risk remained significant and robust in each ethnic group, including whites, blacks, Hispanics, and Asians/Pacific Islanders. When evaluated jointly, the relations of HOMA-IR and HOMA-B with diabetes risk appeared to be independent and additive. HOMA-IR was more strongly associated with an increased risk than were other markers after we excluded those with fasting glucose > or = 126 mg/dl at baseline.High HOMA-IR and low HOMA-B were independently and consistently associated with an increased diabetes risk in a multiethnic cohort of U.S. postmenopausal women. These data suggest the value of HOMA indexes for diabetes risk in epidemiologic studies.
Publication
487
Body composition and physical function in the Women’s Health Initiative Observational StudyJennifer Bea
Bea JW, Going SB, Wertheim BC, Bassford TL, LaCroix AZ, Wright NC, Nicholas JS, Heymsfield SB, Chen Z. Body composition and physical function in the Women’s Health Initiative Observational Study. Prev Med Rep. 2018 May 9;11:15-22. doi: 10.1016/j.pmedr.2018.05.007. eCollection 2018 Sep.
body composition, obese, DXAObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/30065910https://www.whi.org/researchers/bibliography/Manuscripts/ms487.pdf
AS153
Physical function is critical for mobility and quality of life. We hypothesized that higher total lean mass is associated with higher physical function, and body fat inversely associated, among postmenopausal women. Women's Health Initiative Observational Study participants at Pittsburgh, PA; Birmingham, AL; and Tucson-Phoenix, AZ (1993-1998) completed dual-energy X-ray absorptiometry scans and the Rand SF-36 questionnaire at baseline and 3 y (N = 4526). Associations between quartiles (Q1-4) of lean or fat mass and physical function were tested using linear regression, adjusted for demographics, lifestyle factors, medical history, and scanner serial number. At baseline, participants had a mean ± SD age of 63.4 ± 7.4 y and BMI of 27.4 ± 5.8 kg/m2. Higher percent lean mass was positively associated with physical function at baseline (Q4, 83.6 ± 0.6 versus Q1, 74.6 ± 0.7; p < 0.001), while fat mass (kg and %) was inversely associated (e.g., Q4, 73.7 ± 0.7 versus Q1, 84.2 ± 0.7 kg; ptrend < 0.001). Physical function had declined across the cohort at 3 y; the highest relative lean mass quartile at baseline conferred a lesser decline in physical function than the lowest (Q4, -3.3 ± 0.6 versus Q1-7.0 ± 0.6; ptrend < 0.001), while the highest fat mass quartile (% and kg) conferred greater decline (ex. Kg Q4, -6.7 ± 0.7 versus Q1-2.8 ± 0.6; ptrend < 0.001). Increased fat mass (≥5%), but not lean mass, was associated with lower physical function at 3 y (p < 0.001). Adiposity, as well as lean mass, requires consideration in the prediction of physical function among postmenopausal women over time.
Publication
489
Does obesity really make the femur stronger? Bone Mineral Density, geometry and fracture incidence in the Women’s Health Initiative - Observational StudyThomas Beck
Beck TJ, Petit MA, Wu G, Leboff MS, Cauley JA, Chen Z. Does obesity really make the femur stronger? Bone Mineral Density, geometry and fracture incidence in the Women’s Health Initiative - Observational Study.  J Bone Miner Res. 2009 Aug;24(8):1369-79. Epub 2009 Mar 17
none providedObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19292617https://www.whi.org/researchers/bibliography/Manuscripts/ms489.pdf
AS153
Heavier individuals have higher hip BMD and more robust femur geometry, but it is unclear whether values vary in proportion with body weight in obesity. We studied the variation of hip BMD and geometry across categories of body mass index (BMI) in a subset of postmenopausal non-Hispanic whites (NHWs) from the Women's Health Initiative Observational Cohort (WHI-OS). The implications on fracture incidence were studied among NHWs in the entire WHI-OS. Baseline DXA scans of hip and total body from 4642 NHW women were divided into BMI (kg/m(2)) categories: underweight (<18.5), healthy weight (18.5-24.9), overweight (25-29.9), and mild (30-34.9), moderate (35-39.9), and extreme obesity (>40). Femur BMD and indices of bone axial (cross-sectional area [CSA]) and bending strength (section modulus [SM]) were extracted from DXA scans using the hip structure analysis (HSA) method and compared among BMI categories after adjustment for height, age, hormone use, diabetes, activity level, femur neck-shaft angle, and neck length. The association between BMI and incident fracture was studied in 78,013 NHWs from the entire WHI-OS over 8.5 +/- 2.6 (SD) yr of follow-up. Fracture incidence (cases/1000 person-years) was compared among BMI categories for hip alone, central body (hip, pelvis, spine, ribs, and shoulder girdle), upper extremity (humerus and distal), and lower extremity (femur shaft and distal but not hip). Femur BMD, CSA, and SM were larger in women with higher BMI, but values scaled in proportion to lean and not to fat or total body mass. Women with highest BMI reported more falls in the 12 mo before enrollment, more prevalent fractures, and had lower measures of physical activity and function. Incidence of hip fractures and all central body fractures declined with BMI. Lower extremity fractures distal to the hip trended upward, and upper extremity incidence was independent of BMI. BMD, CSA, and SM vary in proportion to total body lean mass, supporting the view that bones adapt to prevalent muscle loads. Because lean mass is a progressively smaller fraction of total mass in obesity, femur BMD, CSA, and SM decline relative to body weight in higher BMI categories. Traumatic forces increase with body weight, but fracture rates at the hip and central body were less frequent with increasing BMI, possibly because of greater soft tissue padding. There was no evident protective effect in fracture rates at less padded distal extremity sites. Upper extremity fractures showed no variation with BMI, and lower extremity fracture rates were higher only in the overweight (BMI = 25-29.9 kg/m(2)).
Publication
492
Cardiovascular risk in women with non-specific chest pain (from the Women’s Health Initiative Hormone Trials)Jennifer Robinson
Robinson JG, Wallace R, Limacher M, Ren H, Cochrane B, Wassertheil-Smoller S, Ockene JK, Blanchette PL, Ko MG. Cardiovascular risk in women with non-specific chest pain (from the Women’s Health Initiative Hormone Trials). Am J Cardiol. 2008 Sep 15;102(6):693-9. Epub 2008 Jul 2.
nonspecific chest pain, non-obstructive coronary angiograms, endothelial dysfunction, coronary heart diseaseClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18773990https://www.whi.org/researchers/bibliography/Manuscripts/ms492.pdf
Women discharged with diagnoses of nonspecific chest pain (NSCP) may be at increased risk for subsequent coronary artery disease (CAD) events. The influence of hormone therapy on NSCP is unknown. The Women's Health Initiative (WHI) enrolled postmenopausal women aged 50 to 79 years. The duration of follow-up was 7.1 years in the WHI Estrogen-Alone trial (E-Alone) and 5.6 years in the WHI Estrogen Plus Progestin trial (E+P). After excluding women with previous cardiovascular disease, 9,427 women in E-Alone and 15,105 women in E+P were included in this analysis. NSCP, defined as having a primary hospital discharge diagnosis of NSCP by International Classification of Diseases, Ninth Revision, code, was reported in 322 women in E-Alone and 249 in E+P. Risks for subsequent CAD events were estimated using intent-to-treat Cox proportional-hazards models stratified by clinic and adjusted for age and other risk factors. In the fully adjusted models of the combined trials, women with NSCP had a twofold greater risk for subsequent nonfatal CAD events, including nonfatal myocardial infarction (2.3% vs 1.7%, hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.11 to 3.98), revascularization (3.5% vs 2.6%, HR 1.99, 95% CI 1.20 to 3.30), and hospitalized angina (3.7% vs 2.3%, HR 2.39, 95% CI 1.46 to 3.92). Hormone therapy did not appear to have a significant effect on either the incidence of NSCP hospitalizations (E-Alone: HR 1.04, 95% CI 0.81 to 1.32; E+P: HR 0.78, 95% CI 0.59 to 1.02) or the risk for a subsequent CAD event. In conclusion, a hospitalization for NSCP doubles the risk for a subsequent CAD event in postmenopausal women over the next 5 to 7 years and identifies them as candidates for aggressive risk factor treatment.
Publication
493
Panic attacks and risk of Incident cardiovascular events among postmenopausal women in the Women’s Health Initiative observational studyJordan Smoller
Smoller JW, Pollack MH, Wassertheil-Smoller S, Jackson RD, Oberman, A, Wong, ND, Sheps D. Panic attacks and risk of Incident cardiovascular events among postmenopausal women in the Women’s Health Initiative observational study. Arch Gen Psychiatry. 2007 Oct;64(10):1153-60.
panic attacks, myocardial ischemia, Holter monitoring, chest painObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17909127https://www.whi.org/researchers/bibliography/Manuscripts/ms493.pdf
Previous studies have documented an association of depression and phobic anxiety with cardiovascular morbidity and mortality, but little is known about the cardiovascular sequelae of panic anxiety.To determine whether panic attacks are associated with risk of cardiovascular morbidity and mortality in postmenopausal women.Prospective cohort survey.Ten clinical centers of the 40-center Women's Health Initiative.A total of 3369 community-dwelling, generally healthy postmenopausal women (aged 51-83 years) enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study who completed a questionnaire about occurrence of panic attacks in the previous 6 months.Cardiovascular/cerebrovascular outcomes (fatal and nonfatal myocardial infarction and stroke) and all-cause mortality were ascertained after a mean of 5.3 years of follow-up.A 6-month history of full-blown panic attacks, endorsed by 10% of postmenopausal women in this cohort, was associated with both coronary heart disease (hazard ratio, 4.20; 95% confidence interval, 1.76-9.99) and the combined end point of coronary heart disease or stroke (hazard ratio, 3.08; 95% confidence interval, 1.60-5.94) after controlling for multiple potential confounders. The hazard ratio for all-cause mortality, excluding those with a history of cardiovascular/cerebrovascular events, was 1.75 (95% confidence interval, 1.04-2.94).Panic attacks are relatively common among postmenopausal women and appear to be an independent risk factor for cardiovascular morbidity and mortality in older women.
Publication
494
Prospective analysis of association between use of statins and melanoma risk in the Women's Health InitiativeDeepa Jagtap
Jagtap D, Rosenberg CA, Martin LW, Pettinger M, Khandekar J, Lane D, Ockene I, Simon MS. Prospective analysis of association between use of statins and melanoma risk in the Women's Health Initiative. Cancer. 2012 Oct 15;118(20):5124-31. doi: 10.1002/cncr.27497. Epub 2012 Mar 20
skin cancer, malignant melanoma, lipid-lowering agents, cancer chemoprevention, statinsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/22434400https://www.whi.org/researchers/bibliography/Manuscripts/ms494.pdf
Melanoma is the most lethal form of skin cancer, with an estimated 68,130 new cases and 8700 deaths in the United States in 2010. The increasing incidence and high death rate associated with metastatic disease support the need to focus on prevention. The authors used data from the Women's Health Initiative (WHI) to assess whether 3-hydroxy-3 methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of melanoma.The study population consisted of 119,726 postmenopausal white women, in which 1099 cases of malignant melanoma were identified over an average (± standard deviation) of 11.6 ± 3.2 years. All diagnoses were confirmed by medical record review and pathology reports. Information on statin use was collected at baseline and during follow-up. Self-administered and interview-administered questionnaires were used to collect information on other risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses investigated the association of any statin use, type, potency, lipophilic status, and duration of use with melanoma.Statins were used by 8824 women (7.4%) at baseline. The annualized rate of melanoma was 0.09% among statin users and 0.09% among nonusers The multivariable adjusted HR for statin users compared with nonusers was 1.14 (95% CI, 0.91-1.43). There were no significant differences in risk based on statin type, potency, category, duration, or in time-dependent models.There was no significant association between statin use and melanoma risk among postmenopausal women in the WHI.
Publication
495
Natural history of pelvic organ prolapse in postmenopausal womenIngrid Nygaard
Bradley CS, Zimmerman MB, Qi Y, Nygaard IE. Natural history of pelvic organ prolapse in postmenopausal women. Obstet Gynecol. 2007 Apr;109(4):848-54.
pelvic organ prolapse, uterine prolapse, pelvic floor disorderClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17400845https://www.whi.org/researchers/bibliography/Manuscripts/ms495.pdf
AS135
To describe the natural history of pelvic organ prolapse and risk factors for changes in vaginal descent in older women.This 4-year prospective observational study included 259 postmenopausal women with a uterus enrolled at one Women's Health Initiative clinical site who completed at least two annual pelvic organ prolapse quantification (POP-Q) examinations. We calculated 1-year and 3-year incidence and resolution risks for prolapse (defined as maximal vaginal descent to or beyond the hymen) and estimated progression and regression rates (1 cm or greater and 2 cm or greater changes in maximal vaginal descent) and risk factors.Mean age was 68.1+/-5.5 years, and median vaginal parity was 4. Seventy-three (28%) women had four exams, 128 (49%) had three exams, and 58 (22%) had two exams. Prolapse waxed and waned yearly in individual women. Overall 1-year and 3-year prolapse incidences were 26% (95% confidence interval [CI] 20-33%) and 40% (95% CI 26-56%); 1-year and 3-year prolapse resolution risks were 21% (95% CI 11-33%) and 19% (95% CI 7-39%). Rates of any change in maximal vaginal descent over time varied depending on baseline measurements. Over 3 years, the maximal vaginal descent increased by at least 2 cm in 11.0% (95% CI 4.9-20.5%) of the women and decreased by at least 2 cm in 2.7% (95% CI 0.3-9.5%). Increasing body mass index and grand multiparity increased the risk for vaginal descent progression.Prolapse progresses and regresses in older women, although rates of vaginal descent progression are slightly greater than regression overall. Obesity is a risk factor for progression in vaginal descent.III.
Publication
496
Hip bone density predicts breast cancer risk independently of Gail score: Results from the Women's Health InitiativeZhao Chen
Chen Z, Arendell L, Aickin M, Cauley J, Lewis CE, Chlebowski R. Hip bone density predicts breast cancer risk independently of Gail score: Results from the Women's Health Initiative. Cancer. 2008 Sep 1;113(5):907-15. Epub 2008 Jul 29.
bond mineral density, breast cancer, SERMSBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18666209https://www.whi.org/researchers/bibliography/Manuscripts/ms496.pdf
The Gail model has been commonly used to estimate a woman's risk of breast cancer within a certain time period. High bone mineral density (BMD) is also a significant risk factor for breast cancer, but it appears to play no role in the Gail model. The objective of the current study was to investigate whether hip BMD predicts postmenopausal breast cancer risk independently of the Gail score.In this prospective study, 9941 postmenopausal women who had a baseline hip BMD and Gail score from the Women's Health Initiative were included in the analysis. Their average age was 63.0 +/- 7.4 years at baseline.After an average of 8.43 years of follow-up, 327 incident breast cancer cases were reported and adjudicated. In a multivariate Cox proportional hazards model, the hazards ratios (95% confidence interval [95% CI]) for incident breast cancer were 1.35 (95% CI, 1.05-1.73) for high Gail score (>or=1.67%) and 1.25 (95% CI, 1.11-1.40) for each unit of increase in the total hip BMD T-score. Restricting the analysis to women with both BMD and a Gail score above the median, a sharp increase in incident breast cancer for women with the highest BMD and Gail scores was found (P < .05).The contribution of BMD to the prediction of incident postmenopausal breast cancer across the entire population was found to be independent of the Gail score. However, among women with both high BMD and a high Gail score, there appears to be an interaction between these 2 factors. These findings suggest that BMD and Gail score may be used together to better quantify the risk of breast cancer.
Publication
499
Prospective analysis of association between use of statins or other lipid-lowering agents and colorectal cancer riskMichael Simon
Simon MS, Rosenberg CA, Rodabough RJ, Greenland P, Ockene I, Roy HK, Lane DS, Cauley JA, Khandekar J. Prospective analysis of association between use of statins or other lipid lowering agents and colorectal cancer risk. Ann Epidemiol. 2012 Jan;22(1):17-27. doi: 10.1016/j.annepidem.2011.10.006. Epub 2011 Nov 4.
colon cancer, HMG CoA Reductase Inhibitors, statins, rectal cancer, colon polypsBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/22056480https://www.whi.org/researchers/bibliography/Manuscripts/Ms499.pdf
To determine whether 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of colorectal cancer.The population included 159,219 postmenopausal women enrolled in the Women's Health Initiative in which 2000 pathologically confirmed cases of colorectal cancer were identified during an average of 10.7 (S.D. 2.9) years. Information on statins was collected at baseline and years 1, 3, 6, and 9. Self- and interviewer-administered questionnaires were used to collect information on other risk factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the use of Cox proportional hazards regression to evaluate the relationship between statin use and risk. Statistical tests were two-sided.Statins were used by 12,030 (7.6%) women at baseline. The annualized colorectal cancer rate was 0.13% among users and 0.12% among nonusers. The multivariable adjusted HR for users versus nonusers was 0.99 (95% confidence interval [CI], 0.83-1.20, p = .95), and 0.79 (95% CI, 0.56-1.11) for users of ≥3 years. In the multivariable adjusted time-dependent model, the HR for lovastatin was 0.62 (95% CI, 0.39-0.99). There was no effect of tumor location, stage or grade.There was a reduction in colorectal cancer risk associated with lovastatin and a nonsignificant association with longer duration of use.
Approved Proposal
500
Results from the long term stability, standardization and quality control for the core analytes at the central laboratory for the WHI programSue Mann
central laboratory analysis, quality control, long term serum pools, core analytesBoth OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms500p.pdf
Publication
501
Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestinGerardo Heiss
Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, Chlebowski RT, Gass M, LaCroix A, Manson JE, Prentice RL, Rossouw J, Stefanick ML; WHI Investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008 Mar 5;299(9):1036-45
none providedClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18319414https://www.whi.org/researchers/bibliography/Manuscripts/ms501.pdf
The Women's Health Initiative (WHI) trial of estrogen plus progestin vs placebo was stopped early, after a mean 5.6 years of follow-up, because the overall health risks of hormone therapy exceeded its benefits.To report health outcomes at 3 years (mean 2.4 years of follow-up) after the intervention was stopped.The intervention phase was a double-blind, placebo-controlled, randomized trial of conjugated equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5 mg daily, in 16,608 women aged 50 through 79 years, recruited by 40 centers from 1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15 730 women.Semi-annual monitoring and outcomes ascertainment continued per trial protocol. The primary end points were coronary heart disease and invasive breast cancer. A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.The risk of cardiovascular events after the intervention was comparable by initial randomized assignments, 1.97% (annualized rate) in the CEE plus MPA (343 events) and 1.91% in the placebo group (323 events). A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group (1.56% [n = 281] vs 1.26% [n = 218]; hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.04-1.48). More breast cancers were diagnosed in women who had been randomly assigned to receive CEE plus MPA vs placebo (0.42% [n = 79] vs 0.33% [n = 60]; HR, 1.27; 95% CI, 0.91-1.78) with a modest trend toward a lower HR during the follow-up after the intervention. All-cause mortality was somewhat higher in the CEE plus MPA than in the placebo group (1.20% [n = 233] vs 1.06% [n = 196]; HR, 1.15; 95% CI, 0.95-1.39). The global index of risks and benefits was unchanged from randomization through March 31, 2005 (HR, 1.12; 95% CI, 1.03-1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention.The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention. A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12% higher in women randomly assigned to receive CEE plus MPA compared with placebo.clinicaltrials.gov Identifier: NCT00000611.
Approved Proposal
502
Menopausal hormone therapy and risk of ovarian cancerGarnet Anderson
none providedClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/ms502p.pdf
Publication
503
Oophorectomy, hormone therapy, and subclinical coronary artery disease in women with hysterectomy: the Women's Health Initiative coronary artery calcium studyMatthew Allison
Allison MA, Manson JE, Langer RD, Carr JJ, Rossouw JE, Pettinger MB, Phillips L, Cochrane BB, Eaton CB, Greenland P, Hendrix S, Hsia J, Hunt JR, Jackson RD, Johnson KC, Kuller LH, Robinson J; Women's Health Initiative and Women's Health Initiative Coronary Artery Calcium Study Investigators. Oophorectomy, hormone therapy, and subclinical coronary artery disease in women with hysterectomy: the Women's Health Initiative coronary artery calcium study. Menopause. 2008 Jul-Aug;15(4 Pt 1):639-47. Epub 2008 May 2
postmenopausal, women, estrogen, calcium, coronary, atherosclerosis, imagingClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18458645https://www.whi.org/researchers/bibliography/Manuscripts/ms503.pdf
W25
Surgical menopause has been associated with an increased risk of coronary heart disease events. In this study, we aimed to determine the associations between coronary artery calcium (CAC) and hysterectomy, oophorectomy, and hormone therapy use with a focus on the duration of menopause for which there was no hormone therapy use.In a substudy of the Women's Health Initiative placebo-controlled trial of conjugated equine estrogens (0.625 mg/d), we measured CAC by computed tomography 1.3 years after the trial was stopped. Participants included 1,064 women with previous hysterectomy, aged 50 to 59 years at baseline. The mean trial period was 7.4 years. Imaging was performed at a mean of 1.3 years after the trial was stopped.Mean age was 55.1 years at randomization and 64.8 years at CAC measurement. In the overall cohort, there were no significant associations between bilateral oophorectomy, years since hysterectomy, years since hysterectomy without taking hormone therapy (HT), years since bilateral oophorectomy, and years of HT use before Women's Health Initiative enrollment and the presence of CAC. However, there was a significant interaction between bilateral oophorectomy and prerandomization HT use for the presence of any CAC (P = 0.05). When multivariable analyses were restricted to women who reported no previous HT use, those with bilateral oophorectomy had an odds ratio of 2.0 (95% CI: 1.2-3.4) for any CAC compared with women with no history of oophorectomy, whereas among women with unilateral or partial oophorectomy, the odds of any CAC was 1.7 (95% CI: 1.0-2.8). Among women with bilateral oophorectomy, HT use within 5 years of oophorectomy was associated with a lower prevalence of CAC.Among women with previous hysterectomy, subclinical coronary artery disease was more prevalent among those with oophorectomy and no prerandomization HT use, independent of traditional cardiovascular disease risk factors. The results suggest that factors related to oophorectomy and the absence of estrogen treatment in oophorectomized women may be related to coronary heart disease.
Publication
504
A comparison of two dietary instruments for evaluating the fat-breast cancer relationshipLaurence Freedman
Freedman LS, Potischman N, Kipnis V, Midthune D, Schatzkin A, Thompson FE, Troiano RP, Prentice R, Patterson R, Carroll R, Subar AF. A comparison of two dietary instruments for evaluating the fat-breast cancer relationship. Int J Epidemiol. 2006 Aug;35(4):1011-21. Epub 2006 May 3.
dietary instruments, comparison,  fat,  breast cancerClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16672309https://www.whi.org/researchers/bibliography/Manuscripts/ms504.pdf
Previous research suggests food diaries may be more efficient than food frequency questionnaires (FFQ) in detecting a dietary fat-breast cancer relationship. We assessed this further using 4 day food records (FRs) and FFQs in a large sample.Participants were from the non-intervention group of the dietary modification component of the Women's Health Initiative Clinical Trial: 603 breast cancer cases and 1206 controls matched on age, clinic, and length of follow-up. Relative risks (RRs) were estimated using unconditional logistic regression, adjusted for confounders and for the selection into the trial of women with an FFQ report exceeding 32% calories from fat. Direct comparison of the statistical power of the two instruments used the standardized log RR. An alternative analysis after removing subjects with missing covariate data was also conducted.The RR estimate for breast cancer in the top quintile of total fat intake, adjusted for confounders and total energy, was 1.82 (P for trend 0.02) for the FR but 0.67 for the FFQ (P for trend 0.24). Following adjustment for selection, estimates were 2.09 (P for trend 0.008) for the FR (alternative: 2.54, P for trend 0.006) and 1.71 (P for trend 0.18) for the FFQ (alternative: 1.24, P for trend 0.41). Similar results were seen for fat subtypes, particularly unsaturated fats. Comparisons showed higher statistical power for the FR than the FFQ (e.g. total fat, P = 0.08: alternative P = 0.01).Alternative instruments, such as FRs, may be preferable to FFQs for evaluating diet-disease relationships in cohort studies. The results support a positive association between dietary fat and breast cancer.
Approved Manuscript
505
Body image satisfaction in postmenopausal womenRebecca Ginsberg
body image, weight cycling, physical activityObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/26219698https://www.whi.org/researchers/bibliography/Manuscripts/Ms505.pdf
Dissatisfaction with one's body image is widespread and can have serious health consequences; however, research about its prevalence and correlates in older women is limited. We analyzed data from 75,256 women participating in the Women's Health Initiative Observational Study, a longitudinal study of postmenopausal women's health. Measures used in the study were collected at baseline and/or the third year of follow-up between 1993 and 2002. The majority of participants (83%) in this study were dissatisfied with their bodies because they perceived themselves as heavier than their ideal. Overall, the multiple and significant correlates of body image dissatisfaction explained 36.2% of the variance in the body image dissatisfaction score, with body mass index (BMI) and change in BMI being the two most important contributors to explaining the variance. The results of this study suggest future research should focus on the utility of interventions to reduce dissatisfaction with body image in postmenopausal women that target either maintenance of a lower BMI through diet and exercise, and/or body acceptance. Further, future research should aim to identify factors in addition to body size that drive body image dissatisfaction.
Publication
506
Estrogen therapy and coronary-artery calcificationJoAnn Manson
Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, Kuller LH, Cochrane BB, Hunt JR, Ludlam SE, Pettinger MB, Gass M, Margolis KL, Nathan L, Ockene JK, Prentice RL, Robbins J, Stefanick ML; WHI and WHI-CACS Investigators. Estrogen therapy and coronary-artery calcification.  N Engl J Med. 2007 Jun 21;356(25):2591-602.
postmenopausal, women, estrogen, calcium, coronary, atherosclerosis, imagingClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17582069https://www.whi.org/researchers/bibliography/Manuscripts/ms506.pdf
W25
Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways. (ClinicalTrials.gov number, NCT00000611.)
Publication
507
Hematopoietic prostaglandin D synthase (HPGDS): A high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancerBrigette Tippin
Tippin BL, Levine AJ, Materi AM, Song WL, Keku TO, Goodman JE, Sansbury LB, Das S, Dai A, Kwong AM, Lin AM, Lin JM, Park JM, Patterson RE, Chlebowski RT, Garavito RM, Inoue T, Cho W, Lawson JA, Kapoor S, Kolonel LN, Le Marchand L, Haile RW, Sandler RS, Lin HJ. Hematopoietic prostaglandin D synthase (HPGDS): a high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancer. Prostaglandins Other Lipid Mediat. 2012 Jan;97(1-2):22-8. doi: 10.1016/j.prostaglandins.2011.07.006. Epub 2011 Jul 28
colorectal neoplasia; hematopoietic prostaglandin D synthase; genetic variants; case-control analysisObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/21821144https://www.whi.org/researchers/bibliography/Manuscripts/ms507.pdf
AS108
Intestinal tumors in Apc(Min/+) mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D(2) (PGD(2)). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187lle isoenzyme (with isoleucine instead of valine at position 187). At 37°C, the wild-type enzyme lost 15% of its activity in 1h, whereas the Val187Ile form remained >95% active. At 50°C, the half life of native HPGDS was 9min, compared to 42 min for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% CI, 0.75-1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model.
Publication
508
Alcohol and folate consumption and risk of benign proliferative epithelial disorders of the breastYan Cui
Cui Y, Page DL, Chlebowski RT, Beresford SA, Hendrix SL, Lane DS, Rohan TE. Alcohol and folate consumption and risk of benign proliferative epithelial disorders of the breast. Int J Cancer. 2007 Sep 15;121(6):1346-51.
benign proliferative epithelial disorders, breast, risk, alcohol, folate, atypical hyperplasiaClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17534897https://www.whi.org/researchers/bibliography/Manuscripts/ms508.pdf
AS130
Alcohol consumption has been associated with increased breast cancer risk and the increase in risk may be attenuated by adequate folate intake. However, their associations with the risk of benign proliferative epithelial disorders (BPEDs) of the breast, possible precursors of breast cancer, are not well understood. To investigate these associations, we conducted a cohort study among 68,132 postmenopausal women participating in the Women's Health Initiative randomized clinical trials. Women were prospectively followed and those reporting a breast procedure (open surgical biopsy or core needle biopsy) had histological sections obtained for central pathology review. A total of 1,792 women with BPED of the breast were identified over an average of 7.8 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence limits (CLs) for the associations of interest. Compared to nondrinkers, total current alcohol intake of 30 g/day or more was not associated with BPED risk (HR = 0.98, 95% CL = 0.70, 1.38). The risk of BPED was not associated with folate intake from diet (highest vs. lowest quartile: HR = 1.10, 95% CL = 0.96, 1.26), from supplements (yes vs. no: HR = 1.05, 95% CL = 0.96, 1.16) or from all sources combined (highest vs. lowest quartile: HR = 1.11, 95% CL = 0.96, 1.27). Furthermore, there was no effect modification between alcohol and folate in relation to the risk of BPED. In conclusion, we observed that alcohol consumption and folate intake were not associated with altered risk of BPED, and that there was no effect modification between them in relation to the risk of BPED.
Publication
509
Cigarette smoking and risk of benign proliferative epithelial disorders of the breast in the Women's Health InitiativeYan Cui
Cui Y, Page DL, Chlebowski RT, Hsia J, Allan Hubbell F, Johnson KC, Rohan TE. Cigarette smoking and risk of benign proliferative epithelial disorders of the breast in the Women's Health Initiative. Cancer Causes Control. 2007 May;18(4):431-8. Epub 2007 Feb 24.
benign proliferative epithelial disorders, breast, risk, cigarette smoking, atypical hyperplasiaClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/17323143https://www.whi.org/researchers/bibliography/Manuscripts/ms509.pdf
AS130
To investigate the association between cigarette smoking and risk of benign proliferative epithelial disorders (BPED) of the breast.We used data from an ancillary study of benign breast disease that is being conducted in the Women's Health Initiative randomized clinical trials among 68,132 postmenopausal women aged 50-79 at recruitment. After following the trial participants for an average of 7.8 years, we had ascertained 294 incident cases with atypical hyperplasia and 1,498 incident cases with non-atypical BPED of the breast. We used Cox proportional hazards models to estimate hazard ratios for the association between cigarette smoking and risk of BPED.Smoking measures, including duration of smoking, intensity of smoking, pack-years of smoking, age at which smoking commenced, and years since quitting smoking, were not associated with risk of BPED overall or by histological subtypes.The null association between cigarette smoking and risk of BPED of the breast suggests that the carcinogenic and antiestrogenic effects of cigarette smoking on the breast might counterbalance each other and that cigarette smoking might have no overall effects on BPED of the breast among postmenopausal women.
Publication
510
Alcohol consumption and the risk of coronary heart disease in women with diabetes: Women’s Health Initiative Observational StudySwapnil Rajpathak
Rajpathak SN, Freiberg MS, Wang C, Wylie-Rosett J, Wildman RP, Rohan TE, Robinson JG, Liu S, Wassertheil-Smoller S. Alcohol consumption and the risk of coronary heart disease in postmenopausal women with diabetes: Women's Health Initiative Observational Study. Eur J Nutr. 2010 Jun;49(4):211-8. Epub 2009 Oct 13
alcohol, coronary heart disease, diabetes, drinking pattern, frequency, alcohol typeObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19823890https://www.whi.org/researchers/bibliography/Manuscripts/ms510.pdf
Although several observational studies have consistently reported an inverse association between moderate alcohol consumption and risk of coronary heart disease (CHD), it is yet not well established if this association also exists among people with type 2 diabetes. The aim of this study is to evaluate the association between the frequency and quantity of alcohol intake and the risk of developing CHD among postmenopausal women with diabetes.We conducted a prospective cohort study, which included 3,198 women with self-reported diabetes and without any history of cardiovascular disease at baseline, in the Women's Health Initiative Observational Study. Alcohol intake was assessed by a semiquantitative food frequency questionnaire. The primary outcome of this study was CHD, which was validated by medical record review. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for the association of alcohol intake and risk of incident CHD while adjusting for several potential confounders.During the 22,546 person-years of follow-up, there were 336 incident cases of CHD. Both frequency and quantity of alcohol intake were inversely associated with the risk of developing CHD. Compared to nondrinkers, the multivariable HRs across categories of frequency of alcohol consumption (<or=0.5, 0.5-2 and >or=2 drinks/week) were 0.89 (95% confidence intervals [CI]: 0.63, 1.26), 0.84 (95% CI: 0.56, 1.25) and 0.65 (95% CI: 0.43, 0.99), respectively (p for trend: 0.04). This association did not appear to differ based on the type of the alcoholic beverage consumed.Moderate alcohol consumption of postmenopausal women with type 2 diabetes may have a benefit on CHD similar to that seen in postmenopausal nondiabetic women. The potential risks of alcohol on noncardiac outcomes may need consideration when recommending alcohol to women with diabetes.
Approved Proposal
513
Alcohol consumption and the risk of cardiovascular disease among black and white women: The effects of current and lifetime patterns of alcohol consumption among participants from the Women’s Health InitiativeMatthew Freiberg
alcohol consumption, CVD, mortality, lifetime drinking history, patterns of alcohol consumptionObservational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms513pv3.pdf
Publication
514
Selected antioxidants and risk of hormone receptor–defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational StudyYan Cui
Cui Y, Shikany JM, Liu S, Yasmeen S, Rohan TE. Selected antioxidants and risk of hormone receptor–defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational Study. Am J Clin Nutr. Am J Clin Nutr. 2008 Apr;87(4):1009-18.
breast cancer, postmenopausal, estrogen receptor, progesterone receptor, micronutrients, folate, carotenoids, vitamin C, vitamin EObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18400726https://www.whi.org/researchers/bibliography/Manuscripts/ms514.pdf
Few studies have evaluated carotenoids and vitamins C and E in association with the risk of breast cancers defined by estrogen receptor (ER) and progesterone receptor (PR) status.We examined the associations between dietary and supplemental intakes of these nutrients and risk of breast cancers jointly defined by both ER and PR status among postmenopausal women.Our investigation was conducted in the Women's Health Initiative Observational Study. After following 84 805 women for an average of 7.6 y, 2879 incident invasive breast cancer cases had been ascertained, of whom 2509 had receptor data. We used Cox proportional hazards models to assess the associations of interest.Dietary alpha-carotene (highest versus lowest quintile: RR = 0.83; 95% CL = 0.70, 0.99; P for trend = 0.019), beta-carotene (highest versus lowest quintile: RR = 0.78; 95% CL = 0.66, 0.94; P for trend = 0.021), and lycopene (highest versus lowest quintile: RR = 0.85; 95% CL = 0.73, 1.00; P for trend = 0.064) were inversely associated with risk of ER+PR+breast cancer, but not with other breast cancer groups jointly defined by ER and PR status. Total or supplemental beta-carotene and dietary intakes of lutein+zeaxanthin and beta-cryptoxanthin were not associated with breast cancers defined by ER and PR status. Vitamin E (regardless of source) and dietary vitamin C were not associated with breast cancer. However, total and supplemental vitamin C intake had weak positive associations with breast cancer overall.Dietary intake of certain carotenoids might be differentially associated with risk of invasive breast cancers jointly defined by ER and PR status among postmenopausal women.
Publication
518
Baseline monograph - forewordJacques Rossouw
Rossouw JE, Anderson GL, Oberman A. Baseline monograph - foreword. Ann Epidemiol. 2003;13:S1-S4
Both OS and CThttps://www.whi.org/researchers/bibliography/Manuscripts/ms518.pdf
Publication
519
Implementation of the Women's Health Initiative study designGarnet Anderson
Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, Shumaker S, Wang CY, Stein E, Prentice RL. Implementation of the Women's Health Initiative study design. Ann Epidemiol. 2003 Oct;13(9 Suppl):S5-17.
Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14575938https://www.whi.org/researchers/bibliography/Manuscripts/ms519.pdf
Publication
520
The Women's Health Initiative recruitment methods and resultsJennifer Hays
Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, Rossouw JE. The Women's Health Initiative recruitment methods and results. Ann Epidemiol. 2003 Oct;13(9 Suppl):S18-77.
Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/14575939https://www.whi.org/researchers/bibliography/Manuscripts/ms520.pdf
W1
Publication
521
The Women's Health Initiative postmenopausal hormone trials: Overview and baseline characteristics of participantsMarcia Stefanick
Stefanick ML, Cochrane BB, Hsia J, Barad DH, Liu JH, Johnson SR. The Women's Health Initiative postmenopausal hormone trials: Overview and baseline characteristics of participants. Ann Epidemiol. 2003 Oct;13(9 Suppl):S78-86.
Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14575940https://www.whi.org/researchers/bibliography/Manuscripts/ms521.pdf
W1
Publication
522
The Women's Health Initiative Dietary Modification trial: Overview and baseline characteristics of participantsCheryl Ritenbaugh
Ritenbaugh C, Patterson RE, Chlebowski RT, Caan B, Fels-Tinker L, Howard B, Ockene J. The Women's Health Initiative Dietary Modification Trial: Overview and baseline characteristics of participants. Ann Epidemiol. 2003 Oct;13(9 Suppl):S87-97.
Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14575941https://www.whi.org/researchers/bibliography/Manuscripts/ms522.pdf
Publication
523
The Women's Health Initiative calcium-vitamin D trial: Overview and baseline characteristics of participantsRebecca Jackson
Jackson RD, LaCroix AZ, Cauley JA, McGowan J. The Women's Health Initiative calcium-vitamin D trial: Overview and baseline characteristics of participants. Ann Epidemiol. 2003 Oct;13(9 Suppl):S98-106.
Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14575942https://www.whi.org/researchers/bibliography/Manuscripts/ms523.pdf
Publication
524
The Women's Health Initiative Observational Study: Baseline characteristics of participants and reliability of baseline measuresRobert Langer
Langer RD, White E, Lewis CE, Kotchen JM, Hendrix SL, Trevisan M. The Women's Health Initiative Observational Study: Baseline characteristics of participants and reliability of baseline measures. Ann Epidemiol. 2003 Oct;13(9 Suppl):S107-21.
Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/14575943https://www.whi.org/researchers/bibliography/Manuscripts/ms524.pdf
W1, W2
Publication
525
Outcomes ascertainment and adjudication methods in the Women's Health InitiativeJ. David Curb
Curb JD, McTiernan A, Heckbert SR, Kooperberg C, Stanford J, Nevitt M, Johnson KC, Proulx-Burns L, Pastore L, Criqui M, Daugherty S, WHI Morbidity and Mortality Committee. Outcomes ascertainment and adjudication methods in the Women's Health Initiative. Ann Epidemiol. 2003 Oct;13(9 Suppl):S122-8.
Both OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/14575944https://www.whi.org/researchers/bibliography/Manuscripts/ms525.pdf
Publication
526
Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the Women’s Health Initiative trials of hormone therapyJacques Rossouw
Rossouw JE, Cushman M, Greenland P, Lloyd-Jones DM, Bray P, Kooperberg C, Pettinger M, Robinson J, Hendrix S, Hsia J. Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the Women’s Health Initiative trials of hormone therapy. Arch Intern Med. 2008 Nov 10;168(20):2245-53.
coronary heart disease, hormone therapy, inflammation, thrombosisClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19001202https://www.whi.org/researchers/bibliography/Manuscripts/ms526.pdf
W6
Clinical trials of postmenopausal hormone therapy (HT) have shown increased risk of coronary heart disease (CHD) in the first few years after initiation of therapy and no overall benefit.This nested case-control study evaluates a range of inflammatory, lipid, thrombotic, and genetic markers for their association with CHD in the 4 years after randomization and assesses whether any of these markers modified or mediated the initially increased risk associated with HT in postmenopausal women aged 50 to 79 years at baseline. Conjugated equine estrogens, 0.625 mg/d, or placebo was given to 10 739 hysterectomized women, and the same estrogen plus medroxyprogesterone acetate, 2.5 mg/d, was given to 16 608 women with an intact uterus.In multivariate-adjusted analyses of 359 cases and 820 controls in the combined trials, baseline levels of 12 of the 23 biomarkers studied were associated with CHD events: interleukin 6, matrix metalloproteinase 9, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, D-dimer, factor VIII, von Willebrand factor, leukocyte count, homocysteine, and fasting insulin. Biomarkers tended to be more strongly associated with CHD in the initial 2 years after randomization. The genetic polymorphism glycoprotein IIIa leu33pro was significantly associated with CHD. Baseline low-density lipoprotein cholesterol interacted significantly with HT so that women with higher levels were at higher risk for CHD when given HT (P = .03 for interaction). The levels of several biomarkers were changed by HT, but these changes did not seem to be associated with future CHD events.Several thrombotic, inflammatory, and lipid biomarkers were associated with CHD events in postmenopausal women, but only low-density lipoprotein cholesterol modified the effect of HT. Further research is needed to identify the mechanisms by which HT increases the risk of CHD.clinicaltrials.gov Identifier: NCT00000611.
Publication
527
Predictors of change in calcium intake in postmenopausal women after osteoporosis screeningKatherine McLeod
McLeod KM, McCann SE, Horvath PJ, Wactawski-Wende J. Predictors of change in calcium intake in postmenopausal women after osteoporosis screening. J Nutr. 2007 Aug;137(8):1968-73.
Bone mineral density, osteoporosis, calcium intake, postmenopausal, screening, dual energy x-ray absorptiometryObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17634272https://www.whi.org/researchers/bibliography/Manuscripts/ms527.pdf
AS98
Osteoporosis is a serious public health concern. Understanding the extent to which a bone density assessment affects change in dietary intake in postmenopausal women is needed. This study investigated whether results of bone density screening tests resulted in reported initiation or change in either dietary and/or supplemental calcium intake. Between 1997 and 2000, dual-energy X-ray absorptiometry (DXA) screening was conducted on 1468 postmenopausal women as part of an ancillary study of the Women's Health Initiative Observational Study in Buffalo, New York. One year after bone density testing, a questionnaire was sent to determine change in lifestyle behaviors and dietary intake. Participants included in this analysis were 923 Caucasian women who had not had a prior bone density screening test, reported no prior diagnosis of osteoporosis and were not taking medication (other than hormone therapy) for osteoporosis. Of these, according to WHO T-score criteria, 36% had osteoporosis, 48% had osteopenia, and 17% had normal bone density. Factors associated (P < 0.05) with increase in calcium intake in crude analyses included: BMI, follow-up consultation with a health care provider, and osteopenia or osteoporosis compared with normal T-score level. In multivariate adjusted analyses, both osteopenia [OR = 2.37, 95% CI (1.45-3.89); P = 0.001] and osteoporosis [OR = 3.86, 95% CI (2.30-6.46); P = <0.001] found on DXA were strong independent predictors of women's decision to start or increase calcium intake. This study provided evidence that the results of osteoporosis DXA screening influence postmenopausal women's decisions to increase calcium intake.
Publication
529
Ambient fine particulate matter exposure and myocardial ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI)Eric Whitsel
Zhang Z, Whitsel EA, Quibrera PM, Smith RL, Liao D, Anderson GL, Prineas RJ. Ambient fine particulate matter exposure and myocardial ischemia in the Environmental Epidemiology of Arrhythmogenesis In the Women’s Health Initiative (EEAWHI). Environ Health Perspect. 2009 May;117(5):751-6. Epub 2009 Jan 23
air pollution, myocardial ischemia / infarction, Bayesian hierarchical models, exposure measurement errorClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19479017https://www.whi.org/researchers/bibliography/Manuscripts/ms529.pdf
AS140
Ambient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated.We studied the association between PM and ischemia among 57,908 Women's Health Initiative clinical trial participants from 1999-2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency's monitor data to estimate concentrations of PM < 2.5 microm (PM(2.5)) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration > or = 120 msec.Overall, 6% of the remaining 55,529 women (52-90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from -14 to 349 microV). PM(2.5) (mean +/- SD) averaged over lag(0-2) was 14 +/- 7 microg/m(3). In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-microg/m(3) increase in lag(0-2) PM(2.5) was associated with a 4% [95% confidence interval (CI), -3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of -2 microV (95% CI, -5 to 0 microV) in lead V3.Short-term PM(2.5) exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST-T abnormalities and decreases in T amplitude.
Publication
530
B vitamin intakes and incidence of colorectal cancer: Results from the Women’s Health Initiative Observational Study cohortStefanie Zschäbitz
Zschäbitz S, Cheng TY, Neuhouser ML, Zheng Y, Ray RM, Miller JW, Song X, Maneval DR, Beresford SA, Lane D, Shikany JM, Ulrich CM. B vitamin intakes and incidence of colorectal cancer: results from the Women's Health Initiative Observational Study cohort. Am J Clin Nutr. 2013 Feb;97(2):332-43. doi: 10.3945/ajcn.112.034736. Epub 2012 Dec 19
colorectal cancer, folate, vitamins B12, B6, B2, alcohol, methylationObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/23255571https://www.whi.org/researchers/bibliography/Manuscripts/Ms530.pdf
AS195
The role of one-carbon metabolism nutrients in colorectal carcinogenesis is not fully understood. Associations might be modified by mandated folic acid (FA) fortification or alcohol intake.We investigated associations between intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and colorectal cancer (CRC) in the Women's Health Initiative Observational Study, stratified by time exposed to FA fortification and alcohol intake.A total of 88,045 postmenopausal women were recruited during 1993-1998; 1003 incident CRC cases were ascertained as of 2009. Quartiles of dietary intakes were compared; HRs and 95% CIs were estimated by Cox proportional hazards models.Dietary and total intakes of vitamin B-6 in quartile 4 compared with quartile 1 (HR: 0.80; 95% CI: 0.66, 0.97 and HR: 0.80; 95% CI: 0.66, 0.99, respectively) and total intakes of riboflavin (HR: 0.81; 95% CI: 0.66, 0.99) were associated with reduced risk of CRC overall and of regionally spread disease. In current drinkers who consumed <1 drink (13 g alcohol)/wk, B vitamin intakes were inversely associated with CRC risk (P-interaction < 0.05). Dietary folate intake was positively associated with CRC risk among women who had experienced the initiation of FA fortification for 3 to <9 y (P-interaction < 0.01).Vitamin B-6 and riboflavin intakes from diet and supplements were associated with a decreased risk of CRC in postmenopausal women. Associations of B vitamin intake were particularly strong for regional disease and among women drinkers who consumed alcohol infrequently. Our study provides new evidence that the increased folate intake during the early postfortification period may have been associated with a transient increase in CRC risk.
Publication
534
Menopausal symptom experience before and after stopping estrogen therapy in the Women’s Health Initiative randomized placebo-controlled trialRobert Brunner
Brunner RL, Aragaki A, Barnabei V, Cochrane BB, Gass M, Hendrix S, Lane D, Ockene J, Woods NF, Yasmeen S, Stefanick M. Menopausal symptom experience before and after stopping estrogen therapy in the Women's Health Initiative randomized, placebo-controlled trial. Menopause. 2010 Sep-Oct;17(5):946-54. doi: 10.1097/gme.0b013e3181d76953. Epub 2010 May 24.
CEE, menopausal symptoms, RCT, estrogen discontinuation, symptom managementClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/20505547https://www.whi.org/researchers/bibliography/Manuscripts/ms534.pdf
The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.
Publication
535
Lipoprotein particle concentrations may explain the absence of coronary protection in the Women's Health Initiative Hormone TrialsJudith Hsia
Hsia J, Otvos JD, Rossouw JE, Wu L, Wassertheil-Smoller S, Hendrix SL, Robinson JG, Lund B, Kuller LH; for the Women's Health Initiative Research Group. Lipoprotein particle concentrations may explain the absence of coronary protection in the Women's Health Initiative Hormone Trials. Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1666-71. Epub 2008 Jul 3.
none providedClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18599797https://www.whi.org/researchers/bibliography/Manuscripts/ms535.pdf
The Women's Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case-control substudy.We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo, and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls. Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001 versus placebo). In contrast, neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration (LDL-P).Postmenopausal hormone therapy-induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the randomized hormone trials.
Publication
536
Sexual satisfaction and cardiovascular disease: The Women's Health InitiativeJennifer McCall-Hosenfeld
McCall-Hosenfeld JS, Freund KM, Legault C, Jaramillo SA, Cochrane BB, Manson JE, Wenger NK, Eaton CB, McNeeley SG, Rodriguez BL, Bonds D. Sexual satisfaction and cardiovascular disease: The Women's Health Initiative. Am J Med. 2008 Apr;121(4):295-301.
sex disorders, sexual dysfunctions, cardiovascular diseases, postmenopauseObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18374688https://www.whi.org/researchers/bibliography/Manuscripts/ms536.pdf
Sexual dysfunction in some men is predictive of occult cardiovascular disease. We investigated whether dissatisfaction with sexual activity, a domain of female sexual dysfunction, is associated with prevalent and incident cardiovascular disease in postmenopausal women.Data from the Women's Health Initiative-Observational Study were used. Subjects who were sexually active in the past year were classified at baseline as sexually satisfied or dissatisfied. We performed multiple logistic regression analyses modeling baseline cardiovascular conditions including myocardial infarction, stroke, coronary revascularization, peripheral arterial disease, congestive heart failure, and angina. We then created Cox proportional hazards models to determine hazard ratios for incident cardiovascular disease by baseline sexual dissatisfaction status.Dissatisfaction with sexual activity at baseline was significantly associated with prevalent peripheral arterial disease (odds ratio 1.44, 95% confidence interval, 1.15-1.84), but not prevalent myocardial infarction, stroke, coronary revascularization including coronary artery bypass graft and percutaneous transluminal coronary angioplasty, or a composite cardiovascular disease variable. The odds of baseline angina were decreased among those reporting sexual dissatisfaction at baseline (odds ratio 0.77, 95% confidence interval, 0.66-0.86). In both unadjusted and adjusted analyses, dissatisfaction with sexual activity was not significantly related to an increased hazard of any cardiovascular disease.Dissatisfaction with sexual activity was modestly associated with an increased prevalence of peripheral arterial disease, even after controlling for smoking status. However, dissatisfaction did not predict incident cardiovascular disease. Although this may represent insensitivity of the sexual satisfaction construct to measure sexual dysfunction in women, it might be due to physiological differences in sexual functioning between men and women.
Publication
538
Electrocardiographic predictors of incident congestive heart failure and all-cause mortality in postmenopausal women: The Women's Health InitiativePentti Rautaharju
Rautaharju PM, Kooperberg C, Larson JC, LaCroix A. Electrocardiographic predictors of incident congestive heart failure and all-cause mortality in postmenopausal women: The Women's Health Initiative. Circulation. 2006 Jan 31;113(4):481-9.
electrocardiography, epidemiology, menopause, womenClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/16449727https://www.whi.org/researchers/bibliography/Manuscripts/Ms538.pdf
Information is limited about ECG predictors of the risk of incident congestive heart failure (CHF), particularly in women without overt manifestations of cardiovascular disease (CVD).We evaluated hazard ratios for incident CHF and all-cause mortality using Cox regression in 38,283 participants of the Women's Health Initiative (WHI) during a 9-year follow-up. All risk models were adjusted for demographic and available clinical and therapeutic variables (multivariable-adjusted models). A backward selection procedure was used to identify dominant predictors among those that were significant as individual ECG predictors. Eleven ECG variables were significant predictors of incident CHF, with none of them having a significant interaction with baseline CVD status. From 6 dominant ECG predictors, wide QRS/T angle had a nearly 3-fold increased risk in multivariable-adjusted single ECG variable models. Two other repolarization variables, STV5 depression and high TV1 amplitude, and 2 QRS-related variables, QRS non-dipolar voltage and myocardial infarction (MI) by ECG, were all associated with &2-fold increase of incident CHF risk. Overall, 11 of the 12 ECG variables were significant predictors of all-cause mortality. Four variables had a significant interaction with CVD status requiring stratification. Three among these 4 were strong, dominant predictors in the CVD group: ECG MI, wide QRS/T angle, and low TV5 amplitude had risk increase from >2-fold to 3-fold, with considerably lower risks in the CVD-free group.Several repolarization variables in postmenopausal women are predictors of the risk of incident CHF and all-cause mortality as important as old ECG MI.
Publication
541
Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: the Women's Health Initiative randomized controlled dietary modification trialLesley Tinker
Tinker LF, Bonds DE, Margolis KL, Manson JE, Howard BV, Larson J, Perri MG, Beresford SAA, Robinson JG, Rodriguez B, Safford MM, Wenger NK, Stevens VJ, Parker LM. Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: the Women's Health Initiative randomized controlled dietary modification trial. Arch Intern Med. 2008 Jul 28;168(14):1500-11.
diabetes mellitus, low-fat dietary pattern, insulin, oral hypoglycemic agents, metabolic syndrome, glycemic index, glycemic loadClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18663162https://www.whi.org/researchers/bibliography/Manuscripts/ms541.pdf
Decreased fat intake with weight loss and increased exercise may reduce the risk of diabetes mellitus in persons with impaired glucose tolerance. This study was undertaken to assess the effects of a low-fat dietary pattern on incidence of treated diabetes among generally healthy postmenopausal women.A randomized controlled trial was conducted at 40 US clinical centers from 1993 to 2005, including 48,835 postmenopausal women aged 50 to 79 years. Women were randomly assigned to a usual-diet comparison group (n = 29,294 [60.0%]) or an intervention group with a 20% low-fat dietary pattern with increased vegetables, fruits, and grains (n = 19,541 [40.0%]). Self-reported incident diabetes treated with oral agents or insulin was assessed.Incident treated diabetes was reported by 1303 intervention participants (7.1%) and 2039 comparison participants (7.4%) (hazard ratio, 0.96; 95% confidence interval, 0.90-1.03; P = .25). Weight loss occurred in the intervention group, with a difference between intervention and comparison groups of 1.9 kg after 7.5 years (P < .001). Subgroup analysis suggested that greater decreases in percentage of energy from total fat reduced diabetes risk (P for trend = .04), which was not statistically significant after adjusting for weight loss.A low-fat dietary pattern among generally healthy postmenopausal women showed no evidence of reducing diabetes risk after 8.1 years. Trends toward reduced incidence were greater with greater decreases in total fat intake and weight loss. Weight loss, rather than macronutrient composition, may be the dominant predictor of reduced risk of diabetes.
Publication
542
Enrollment in a brain magnetic resonance study: Results from the Women's Health Initiative Memory Study Magnetic Resonance Imaging Study (WHIMS-MRI)Mark Espeland
Jaramillo SA, Felton D, Andrews L, Desiderio L, Hallarn RK, Jackson SD, Coker LH, Robinson JG, Ockene JK, Espeland MA; Women's Health Initiative Memory Study Research Group. Enrollment in a brain magnetic resonance study: results from the Women’s Health Initiative Memory Study Magnetic Resonance Imaging Study (WHIMS-MRI). Acad Radiol. 2007 May;14(5):603-12.
WHIMS MRI, recruitment, consentMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17434074https://www.whi.org/researchers/bibliography/Manuscripts/ms542.pdf
AS183
The rates of enrollment of volunteers for brain magnetic resonance imaging (MRI) studies vary by demographic and clinical characteristics. We use data from a large MRI study to identify factors associated with differential enrollment and to examine potential biases this may produce in study results.Results from recruitment of 1,431 women into the MRI substudy of the Women's Health Initiative Memory Study (WHIMS-MRI) are described. A sensitivity analysis was conducted to estimate the degree of bias associated with missing data on estimates of risk factor relationships.Of 2,345 women contacted from an established cohort of women older than 70 years of age, 72% consented to undergo screening for WHIMS-MRI. Scanning was ultimately completed on 61%. Completion rates varied according to a range of sociodemographic, lifestyle, and clinical characteristics that may be related to study outcomes. Plausible levels of selective enrollment in magnetic resonance imaging studies may produce moderate biases (< +/-20%) in characterizations of risk factor relationships. Adverse events, such as claustrophobia, occurred during 1.7% of the attempted scans and, in 0.8% of instances, led to lost data.Enrollment of older women into brain imaging studies is feasible, although selection biases may limit how well study cohorts reflect more general populations.
Approved Proposal
543
Insulin-like growth hormone-1, risk factors, and risk for hip fracture in postmenopausal womenRebecca Jackson
 hip fracture, IGF-1; osteoporosis; menopause; IGF-BP-3Observational Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/ms543p.pdf
AS90
Publication
544
Menstrual and reproductive history, postmenopausal hormone use, and risk of benign proliferative epithelial disorders of the breast: A cohort studyYan Cui
Cui Y, Page DL, Lane DS, Rohan TE. Menstrual and reproductive history, postmenopausal hormone use, and risk of benign proliferative epithelial disorders of the breast: A cohort study. Breast Cancer Res Treat. 2009 Mar;114(1):113-20. Epub 2008 Mar 22
benign proliferative epithelial disorders, breast, risk, age at menarche, age at menopause, oral contraceptive use, age at first live birth, age at first full-term pregnancy, parityClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/18360772https://www.whi.org/researchers/bibliography/Manuscripts/ms544.pdf
AS130
Menstrual and reproductive history and postmenopausal hormone use are well-established risk factors for breast cancer. However, previous studies that have assessed these factors in association with risk of benign proliferative epithelial disorders (BPED) of the breast, putative precursors of breast cancer, have yielded inconsistent findings. To investigate these associations, we conducted a cohort study among 68,132 postmenopausal women enrolled in the Women's Health Initiative randomized clinical trials. Women were prospectively followed and those reporting an open surgical biopsy or a core needle biopsy had histological sections obtained for centralized pathology review. Over an average of 7.8 years of follow-up, we identified 1,792 women with BPED of the breast. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence limits (CLs) for the associations of interest. Menstrual and reproductive histories were not associated with risk of BPED of the breast, overall or by histological subtype. Women who had used postmenopausal hormones for 15 years or more had a two-fold increase in risk of BPED of the breast compared to women who had never used postmenopausal hormones (HR = 2.03 95% CL = 1.73, 2.38) and the increase in risk was observed for both BPED of the breast without atypia and for atypical hyperplasia. Furthermore, the risk of BPED of the breast decreased with time since cessation of use so that there was essentially no increase in risk 5 or more years after ending use (HR for stopping >or=5 years earlier = 0.96, 95%CL = 0.79, 1.16; HR for stopping <5 years earlier = 1.32, 95% CL = 1.08,1.61).
Approved Proposal
546
Predictors of incident dementia in postmenopausal women enrolled in a trial of hormone therapy: The Women’s Health Initiative Memory StudyLaura Coker
dementia, Alzheimer’s disease, cerebrovascular diseaseMemory Studyhttps://www.whi.org/researchers/bibliography/Manuscripts/Ms546p.pdf
AS39
Publication
547
Calcium plus vitamin D supplementation has limited effects on femoral geometric strength in older postmenopausal women: The Women's Health InitiativeRebecca Jackson
Jackson RD, Wright NC, Beck TJ, Sherrill D, Cauley JA, Lewis CE, Lacroix AZ, Leboff MS, Going S, Bassford T, Chen Z. Calcium plus vitamin D supplementation has limited effects on femoral geometric strength in older postmenopausal women: The Women's Health Initiative. Calcif Tissue Int. 2011 Mar;88(3):198-208. doi: 10.1007/s00223-010-9449-x. Epub 2011 Jan 21
none providedBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/21253715https://www.whi.org/researchers/bibliography/Manuscripts/ms547.pdf
AS153
Calcium plus vitamin D (CaD) supplementation has a modest but significant effect on slowing loss of femoral bone mass and reducing risk of hip fractures in adherent postmenopausal women. The goal of this study was to determine if CaD supplementation influences hip structural parameters that are associated with fracture risk. We studied 1,970 postmenopausal women enrolled in the Women's Health Initiative randomized controlled trial of CaD at one of three bone mineral density (BMD) clinical centers. Hip structural analysis software measured BMD and strength parameters on DXA scans at three regions: femoral narrow neck, intertrochanter, and shaft. Random effects models were used to test the average differences in hip BMD and geometry between intervention and placebo. There was greater preservation of hip BMD at the narrow neck with CaD relative to placebo across 6 years of intervention. CaD also altered the underlying cross-sectional geometry at the narrow neck in the direction of greater strength, with small increases in cross-sectional area and section modulus and a decrease in buckling ratio with CaD relative to placebo. While trends at both the intertrochanter and shaft regions were similar to those noted at the narrow neck, no significant intervention effects were evident. There was no significant interaction of CaD and age or baseline calcium levels for hip structural properties. CaD supplementation is associated with modest beneficial effects on hip structural features at the narrow neck, which may explain some of the benefit of CaD in reducing hip fracture risk.
Publication
549
Semiparametric estimation exploiting covariate independence in two-phase randomized trialsJames Dai
Dai JY, LeBlanc M, Kooperberg C. Semiparametric estimation exploiting covariate independence in two-phase randomized trials. Biometrics. 2009 Mar;65(1):178-87. Epub 2008 May 13.
none providedBoth OS and CThttp://www.ncbi.nlm.nih.gov/pubmed/18479485https://www.whi.org/researchers/bibliography/Manuscripts/ms549.pdf
Recent results for case-control sampling suggest when the covariate distribution is constrained by gene-environment independence, semiparametric estimation exploiting such independence yields a great deal of efficiency gain. We consider the efficient estimation of the treatment-biomarker interaction in two-phase sampling nested within randomized clinical trials, incorporating the independence between a randomized treatment and the baseline markers. We develop a Newton-Raphson algorithm based on the profile likelihood to compute the semiparametric maximum likelihood estimate (SPMLE). Our algorithm accommodates both continuous phase-one outcomes and continuous phase-two biomarkers. The profile information matrix is computed explicitly via numerical differentiation. In certain situations where computing the SPMLE is slow, we propose a maximum estimated likelihood estimator (MELE), which is also capable of incorporating the covariate independence. This estimated likelihood approach uses a one-step empirical covariate distribution, thus is straightforward to maximize. It offers a closed-form variance estimate with limited increase in variance relative to the fully efficient SPMLE. Our results suggest exploiting the covariate independence in two-phase sampling increases the efficiency substantially, particularly for estimating treatment-biomarker interactions.
Publication
550
Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal womenSimin Liu
Song Y, You NC, Hsu YH, Sul J, Wang L, Tinker L, Eaton CB, Liu S. Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal women. Hum Mol Genet. 2007 Dec 1;16(23):2960-71. Epub 2007 Sep 12.
Calpain-10 (CAPN10), haplotype, type 2 diabetes, the Women’s Health Initiative Observational Study (WHI-OS)Observational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/17855447https://www.whi.org/researchers/bibliography/Manuscripts/ms550.pdf
AS132
Calpain-10 (CAPN10) protein may play a role in glucose metabolisms, pancreatic beta-cell insulin secretion and thermogenesis. Emerging evidence has implicated a role of CAPN10 genetic variants in the risk of type 2 diabetes mellitus (T2DM). Previous association studies, however, have focussed only on several variants initially reported and provided inconsistent results. We conducted a large nested case-control study to comprehensively investigate the associations between common variations in CAPN10 gene and T2DM risk among postmenopausal women aged 50-79 years from the Women's Health Initiative Observational Study. After comprehensive screening in 244 randomly chosen control samples (n = 61 for each of four ethnic groups), we selected a total of 12 tagging single nucleotide polymorphisms (tSNPs) spanning 91 kb in CAPN10 and genotyped them in 1543 diabetes cases and 2132 matched controls (including 968 cases and 968 controls for whites, 366 and 732 for blacks, 152 and 303 for Hispanics and 98 and 195 for Asian/Pacific Islanders). There were no significant associations between any individual tSNP and T2DM, within either the full study sample or any specific ethnic group. Nor was there any evidence of association between common CAPN10 haplotypes and diabetes risk (global tests for differences in risk were P = 0.31 for overall common haplotypes, P = 0.44 for haplotypes in block 1 and P = 0.37 for haplotypes in block 2). In conclusion, we did not observe any significant associations of the common SNPs or haplotypes across the CAPN10 gene with diabetes risk in our large and ethnically diverse cohort of postmenopausal women.
Publication
551
Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women’s Health Initiative StudyJordan Smoller
Smoller JW, Allison M, Cochrane BB, Curb JD, Perlis RH, Robinson JG, Rosal MC, Wenger NK, and Wassertheil-Smoller S. Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women’s Health Initiative Study. Arch Intern Med. 2009;169(22):2128-2139
SSRI, selective serotonin reuptake inhibitors, depression, cardiovascular disease, anti-depressantsObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/20008698https://www.whi.org/researchers/bibliography/Manuscripts/ms551.pdf
Antidepressants are commonly prescribed medications, but their effect on cardiovascular morbidity and mortality remains unclear.Prospective cohort study of 136 293 community-dwelling postmenopausal women in the Women's Health Initiative (WHI). Women taking no antidepressants at study entry and who had at least 1 follow-up visit were included. Cardiovascular morbidity and all-cause mortality for women with new antidepressant use at follow-up (n = 5496) were compared with those characteristics for women taking no antidepressants at follow-up (mean follow-up, 5.9 years).Antidepressant use was not associated with coronary heart disease (CHD). Selective serotonin reuptake inhibitor (SSRI) use was associated with increased stroke risk (hazard ratio [HR],1.45, [95% CI, 1.08-1.97]) and all-cause mortality (HR,1.32 [95% CI, 1.10-1.59]). Annualized rates per 1000 person-years of stroke with no antidepressant use and SSRI use were 2.99 and 4.16, respectively, and death rates were 7.79 and 12.77. Tricyclic antidepressant (TCA) use was associated with increased risk of all-cause mortality (HR,1.67 [95% CI, 1.33-2.09]; annualized rate, 14.14 deaths per 1000 person-years). There were no significant differences between SSRI and TCA use in risk of any outcomes. In analyses by stroke type, SSRI use was associated with incident hemorrhagic stroke (HR, 2.12 [95% CI, 1.10-4.07]) and fatal stroke (HR, 2.10 [95% CI, 1.15-3.81]).In postmenopausal women, there were no significant differences between SSRI and TCA use in risk of CHD, stroke, or mortality. Antidepressants were not associated with risk of CHD. Tricyclic antidepressants and SSRIs may be associated with increased risk of mortality, and SSRIs with increased risk of hemorrhagic and fatal stroke, although absolute event risks are low. These findings must be weighed against quality of life and established risks of cardiovascular disease and mortality associated with untreated depression.
Publication
554
Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational StudySimin Liu
Hsu Y, Niu T, Song Y, Tinker L, Kuller LH, Liu S. Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study. Diabetes. 2008 Apr;57(4):1101-7. Epub 2008 Jan 25.
UCP2, type 2 diabetes, the Women’s Health Initiative –Observational Study (WHI-OS), haplotypeObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/18223008https://www.whi.org/researchers/bibliography/Manuscripts/ms554.pdf
AS132
Mitochondrial uncoupling proteins (UCPs) are involved in body weight regulation and glucose homeostasis. Genetic variants in the UCP2-UCP3 gene cluster, located on chromosome 11q13, may play a significant role in the development of type 2 diabetes.We conducted a comprehensive assessment of common single nucleotide polymorphisms (SNPs) at the 70-kb UCP2-UCP3 gene cluster in relation to type 2 diabetes risk in a prospective, case-control study nested in the Women's Health Initiative Observational Study, an ethnically diverse cohort of postmenopausal women including Caucasian, African, Hispanic, and Asian American subjects. We genotyped 14 tag SNPs in 1,584 incident type 2 diabetes case and 2,198 control subjects matched by age, ethnicity, clinical center, time of blood draw, and length of follow-up.We identified a haplotype set (rs591758-rs668514- rs647126-rs1800006, spanning the UCP2-UCP3 intergenic and UCP3 regions) as significantly associated with greater type 2 diabetes risk (nominal P = 0.0011, permutation P = 0.046) in Caucasian women, especially among overweight Caucasians (BMI >25 kg/m(2)) (nominal P = 0.0006, permutation P = 0.032). Compared with the most common haplotype (h1010 as the referent), haplotype h0001 (19.5% in control subjects) had odds ratios of 2.0 (95% CI 1.13-3.37) in Caucasians and 3.8 (1.44-9.93) in Caucasian overweight women. Similar haplotype-type 2 diabetes association was also observed among Hispanic women who were overweight.These findings suggest a role of UCP2-UCP3 gene cluster haplotypes in diabetes; in particular, the effects of the high-risk haplotypes were more apparent in overweight Caucasian women. These data warrant further confirmation in future prospective and experimental studies.
Publication
555
Common genetic variants in Peroxisome Proliferator-Activated Receptor-γ (PPARG) and Type 2 Diabetes risk among Women's Health Initiative postmenopausal womenKatie Chan
Chan KH, Niu T, Ma Y, You NC, Song Y, Sobel EM, Hsu YH, Balasubramanian R, Qiao Y, Tinker L, Liu S. Common genetic variants in Peroxisome Proliferator-Activated Receptor-γ (PPARG) and Type 2 Diabetes risk among Women's Health Initiative postmenopausal women. J Clin Endocrinol Metab. 2013 Mar;98(3):E600-4. doi: 10.1210/jc.2012-3644. Epub 2013 Feb 5
PPAR gamma, type 2 Diabetes Mellitus, genotype, haplotype, association studiesObservational Studyhttp://www.ncbi.nlm.nih.gov/pubmed/?term=23386649https://www.whi.org/researchers/bibliography/Manuscripts/Ms555.pdf
AS132
Peroxisome proliferator-activated receptor-γ (PPARG) plays a pivotal role in adipogenesis and glucose homeostasis.We investigated whether PPARG gene variants were associated with type 2 diabetes (T2D) risk in the multiethnic Women's Health Initiative (WHI).We assessed PPARG single-nucleotide polymorphisms (SNPs) in a case-control study nested in the prospective WHI observational study (WHI-OS) (1543 T2D cases and 2170 matched controls). After identifying 24 tagSNPs, we used multivariable logistic regression models and haplotype-based analyses to estimate these tagSNP-T2D associations. Single-SNP analyses were also conducted in another study of 5642 African American and Hispanic American women in the WHI SNP Health Association Resource (WHI-SHARe).We found a borderline significant association between the Pro12Ala (rs1801282) variant and T2D risk in WHI-OS [odds ratio (OR) 0.51, 95% confidence interval (CI) 0.31-0.83, P = .01, combined group, additive model; P = .04, Hispanic American] and WHI-SHARe (OR 0.25, 95% CI 0.08-0.77, P = .02, Hispanic American) participants. In promoter region, rs6809631, rs9817428, rs10510411, rs12629293, and rs12636454 were also associated with T2D risk (range ORs 0.68-0.78, 95% CIs 0.52-0.91 to 0.60-1.00, P ≤ .05) in WHI-OS, in which rs9817428 was replicated in then WHI-SHARe Hispanic American group (P = .04).The association between PPARG Pro12Ala SNP and increased T2D susceptibility was confirmed, with Pro12 as risk allele. Additional significant loci included 5 PPARG promoter variants.
Approved Manuscript
556
Obesity and pelvic organ prolapse (POP): A secondary analysisKatharine O'Dell
Vaginal prolapse, obesity, obesity measures, cystocele, rectoceleClinical Trial
Approved Proposal
557
Characteristics of the built environment in Seattle and weight change over timeAlyson Littman
built environment, obesity, physical activity, walking, land-use mix, street connectivity, densityClinical Trialhttps://www.whi.org/researchers/bibliography/Manuscripts/ms557p.pdf
Publication
558
The relationship between cognitive function and physical performance in older women:  Results from the Women's Health Initiative Memory StudyHal Atkinson
Atkinson HH, Rapp SR, Williamson JD, Lovato J, Absher JR, Gass M, Henderson VW, Johnson KC, Kostis JB, Sink KM, Mouton CP, Ockene JK, Stefanick ML, Lane DS, Espeland MA. The relationship between cognitive function and physical performance in older women:  Results from the Women's Health Initiative Memory Study. J Gerontol A Biol Sci Med Sci. 2010 Mar;65(3):300-6. doi: 10.1093/gerona/glp149. Epub 2009 Sep 29
cognition, physical performance, function, cognitive impairment, gait speedMemory Studyhttp://www.ncbi.nlm.nih.gov/pubmed/19789197https://www.whi.org/researchers/bibliography/Manuscripts/ms558.pdf
AS39
Cognitive function and physical performance are associated, but the common sequence of cognitive and physical decline remains unclear.In the Women's Health Initiative Memory Study (WHIMS) clinical trial, we examined associations at baseline and over a 6-year follow-up period between the Modified Mini-Mental State (3MS) Examination and three physical performance measures (PPMs): gait speed (meters/second), chair stands (number of stands in 15 seconds), and grip strength (kilograms). Using mixed models, we examined the baseline 3MS as predictor of change in PPM, change in the 3MS as predictor of change in PPM, and baseline PPM as predictors of 3MS change.Among 1,793 women (mean age = 70.3 years, 89% white, and mean 3MS score = 95.1), PPM were weakly correlated with 3MS-gait speed: r = .06, p = .02; chair stands: r = .09, p < .001; and grip strength: r = .10, p < .001. Baseline 3MS score was associated with subsequent PPM decline after adjustment for demographics, comorbid conditions, medications, and lifestyle factors. For every SD (4.2 points) higher 3MS score, 0.04 SD (0.04 m/s) less gait speed and 0.05 SD (0.29 kg) less grip strength decline is expected over 6 years (p </= .01 both). Changes in 3MS and PPM were associated, particularly with chair stands and grip strength (p < .003 both). Baseline PPMs were not associated with subsequent 3MS change.Baseline global cognitive function and change in global cognitive function were associated with physical performance change, but baseline physical performance was not associated with cognitive change in this cohort. These analyses support the hypothesis that cognitive decline on average precedes or co-occurs with physical performance decline.
Publication
560
Loop diuretic use and fracture in postmenopausal women: Findings from the Women’s Health InitiativeLaura Carbone
Carbone LD, Johnson KC, Bush AJ, Robbins J, Larson JC, Thomas A, LaCroix AZ. Loop diuretic use and fracture in postmenopausal women: Findings from the Women’s Health Initiative.  Arch Intern Med. 2009 Jan 26;169(2):132-40.
CHF, diuretics, spironolactone, furosemide, fractures, thiazidesClinical Trialhttp://www.ncbi.nlm.nih.gov/pubmed/19171809https://www.whi.org/researchers/bibliography/Manuscripts/ms560.pdf
The relationship of loop diuretics to bone mineral density (BMD), falls, and fractures in postmenopausal women has not been established.We examined whether loop diuretics are associated with changes in BMD, falls, and fractures in women enrolled in the Women's Health Initiative. We included the 133,855 women (3411 users and 130,444 nonusers of loop diuretics) who were enrolled in the WHI from October 29, 1993 to December 31, 1998 and determined incident falls and fractures for a mean of 7.7 years. Women who had BMD measurements at baseline and at year 3 (300 users and 9124 nonusers of loop diuretics) were also examined.After adjustment for covariates, no significant association was found between ever use of loop diuretics and total (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.00-1.19), hip (HR, 1.21; 95% CI, 0.91-1.60), and clinical vertebral fractures (HR, 1.17; 95% CI, 0.92-1.48) and falls (1.02; 0.96-1.08). An increased risk was found for other clinical fractures (1.16; 1.01-133) and total fractures (1.16; 1.03-1.31) with more than 3 years' use of loop diuretics. The BMD changes were not associated with loop diuretic use.After adjustment for confounding variables, no significant association was found between ever use of loop diuretics and changes in BMD, falls, and fractures. Loop diuretics were used by women in poor health who were already at risk for fractures. However, prolonged use of loop diuretics was associated with higher