Frequently Asked Questions about the Estrogen-Alone Findings

These questions and answers supplement the April 14, 2004 New England Journal of Medicine publication on the effects of Estrogen-Alone.
  1. What was the hormone used in the Estrogen-Alone study?
  2. Why was the Estrogen-Alone study stopped?
  3. What were the key findings from the Estrogen-Alone study?
  4. How many women were affected by disease events?
  5. How are these new results different from the information that was released in July 2002?
  6. As an Estrogen-Alone participant, why did I need to fill out a Medical History Update before being told if I was in the active hormone or placebo group?
  7. Why do I need to return my unused Estrogen-Alone study pills?
  8. Why are you asking all Estrogen-Alone participants to continue follow-up activities after they stop their study pills?
  9. What should I do about symptoms that I get after stopping the Estrogen-Alone study pills?
  10. Do these findings affect the status of any other WHI program?
  11. I’m taking prescription hormones. What should I do?
  12. What should I tell my health care provider about this new information?
  13. Where can I find out more information about the Estrogen-Alone findings?
  14. What is the WHI Extension Study?
1. What was the hormone used in the Estrogen-Alone study?
Women in the Estrogen-Alone study were randomized to take either a placebo pill or an active pill containing 0.625 mg of conjugated equine estrogens (CEE, commonly known as Premarin®) each day.The CEE was taken alone, without the addition of a progestin. Estrogen-Alone participants had a hysterectomy before joining the WHI, so they did not need to worry about estrogen effects on endometrial (uterine) cancer.
Women in the Estrogen-Plus-Progestin study were randomized to take either a placebo pill or this same hormone, CEE, plus 2.5 mg medroxyprogesterone acetate (CEE+MPA; commonly known as Prempro®) each day.Because participants in this other Hormone Program study still had a uterus, a progestin (MPA) was added to the CEE to protect against endometrial (uterine) cancer.
2. Why was the Estrogen-Alone study stopped?
  • After nearly 7 years of follow-up, study results show that CEE does not appear to affect the risk of heart disease.
  • At the same time, CEE appears to increase the risk of stroke, a clear risk.
  • CEE does not appear to increase the risk of breast cancer.
  • The National Institutes of Health (NIH) believes that enough data have been obtained in this study to provide an overall assessment of the risks and benefits of CEE and that these findings are not likely to change if the Estrogen-Alone study were continued for another year.
  • The NIH believes that an increased risk of stroke is not acceptable in healthy women in a research study, especially if CEE does not prevent heart disease.
3. What were the key findings from the Estrogen-Alone study?
  • Women in the CEE group had more strokes than those in the placebo group.
  • Women in the CEE group had fewer hip fractures than those in the placebo group.
  • Fewer women in the CEE group had breast cancer. These findings are considered uncertain. We may have more information about these effects when we analyze the medical history update forms that you filled out after all Estrogen-Alone study pills were stopped.
  • The effect of CEE on blood clots was also uncertain.
  • CEE had no effect (neutral) on heart attacks, colorectal cancer, and deaths.
4. How many women were affected by disease events?
Referring to the graph on the WHI Hormone Program Update (2004), for every 10,000 women taking CEE each year, there were:
  • 12 more strokes. (There were 44 strokes per 10,000 women per year in the CEE group and 32 strokes per 10,000 women per year in the placebo group.)
  • 7 more blood clots to the legs and lungs combined (28 CEE, 21 placebo)—these effects are considered uncertain.
  • 3 more deaths (81 CEE, 78 placebo)—these effects are neutral (no effect of CEE).
  • 1 more colorectal cancer (17 CEE, 16 placebo)—neutral.
  • 5 fewer heart attacks (49 CEE, 54 placebo)—neutral.
  • 7 fewer invasive breast cancers (26 CEE, 33 placebo)—uncertain.
  • 6 fewer hip fractures (11 CEE, 17 placebo)—benefit. Not shown on the Update graph were 56 fewer total fractures.
Analysis of the data included a “global index” for assessing the balance of risks and benefits overall. The global index compares the number of women who had any of the following serious health conditions: heart attacks, stroke, blood clots in the lungs, breast cancer, colorectal cancer, hip fracture, and deaths from other causes. Although it is not shown on the Update graph, the global index was not different in the two groups. The number of women who had any of the health conditions was about equal in the CEE and placebo groups, so the benefits did not outweigh the risks, in terms of disease prevention.
5. How are these new results different from the information that was released in July 2002?
There are two studies in the WHI Hormone Program. These new findings come from the Estrogen-Alone (E-Alone) study. Findings from the Estrogen-Plus-Progestin (E+P) study were released in July 2002. There are many differences between these two studies:
  • Women who joined the WHI Hormone Program were enrolled in the E-Alone or E+P study depending on whether or not they had a hysterectomy before joining. We did this because, when health care providers prescribe hormones to women with a uterus, progestin is usually added to estrogen to protect against endometrial (uterine) cancer. Therefore, the hormone pills used in the two studies were different.
  • Women in the two studies had different health characteristics when they joined the WHI Hormone Program, even before they started taking study pills. For example, women in the E-Alone trial were at higher risk for a heart attack and stroke, because they had higher blood pressure and weighed more than women in the E+P trial. More women in the E-Alone trial had used hormone therapy in the past, before they joined WHI.
  • The average follow-up in the two studies was different (5.6 years total in the E+P study; 6.8 years in the E-Alone study).
6. As an Estrogen-Alone participant, why did I need to fill out a Medical History Update before being told if I was in the active hormone or placebo group?
We wanted to make sure that we have information about any changes in your health since the last time you filled out the form. When we do more detailed analyses, we want to have as much health information as possible covering the period up until all Estrogen-Alone study pills were stopped.
We also needed to make sure that the updated information was collected in the same way as it always had been. We did not give out study group information before you completed the form for the same reason that neither you nor the WHI staff knew your study group when you were first randomized. Avoiding any possible influence—by researchers or participants—on the data we collect is important to make sure that the study is done scientifically and that the study results can be trusted.
Even if you stopped your Estrogen-Alone study pills before March 1, 2004, your health update is important because we analyze all of the data from all participants who joined the study. This is why we told you at the beginning of the study that no one can take your place, and it is another way that we make sure the study is done scientifically.
7. Why do I need to return my unused Estrogen-Alone study pills?
As always, we need to acount for all study pills and make sure that everyone in the study has stopped.
8. Why are you asking all Estrogen-Alone participants to continue follow-up activities after they stop their study pills?
It is important that all Hormone Program participants continue to have their yearly mammograms to detect any possible breast cancer as early as possible. Annual mammograms are recommended for a woman’s own safety.
Continuing WHI clinic contacts are also important so that we can monitor your health. These clinic contacts and the health updates you complete help us monitor longer term effects of estrogen alone and learn how effects change after stopping. This question can be best answered if all Estrogen-Alone participants—those taking placebo pills and active CEE—continue clinic contacts up to the very last scheduled contact.
9. What should I do about symptoms that I get after stopping the Estrogen-Alone study pills?
You should contact your personal health care provider, who can advise you about how to manage
symptoms after stopping hormones.
If you do not have a personal health care provider, your WHI clinic staff can help you find one.
10. Do these findings affect the status of any other WHI program?
This information does not affect any other WHI program. Specifically:
  • Estrogen-Plus-Progestin participants should continue follow-up contacts, as has been done since study pills were stopped.
  • Calcium and Vitamin D participants should continue taking study pills and have follow-up contacts, as before.
  • Dietary study participants should continue to participate and have clinic contacts, as before.
  • Observational Study participants should continue to complete forms received in the mail, as before.
These findings help point out how important all WHI participants are. The WHI continues to be a landmark study that is answering critical questions about women’s health, answers that no other study is prepared to address.
11. I’m taking hormones prescribed by my health care provider. What should I do?
You should contact your personal health care provider to talk about the reasons you are taking prescription hormones and your individual risk profile.
Your health care provider can advise you about your own use of hormones based on current medical guidelines.
12. What should I tell my health care provider about this new information?
We suggest that you share the information you have received, and any updates, with your health care provider.
WHI staff can also give you a letter to take to your health care providers. If you would like, we can mail the letter and information update directly to your provider.
You can also let your provider know that the scientific paper was published in The Journal of the American Medical Association (JAMA) in its April 14, 2004 issue. An abstract of this paper is available on the JAMA website.
13. Where can I find out more information about the Estrogen-Alone findings?
In addition to the WHI Hormone Program Update and this WHI participant website, the National Heart, Lung, and Blood Institute (NHLBI) has a special WHI website at http://www.nhlbi.nih.gov/whi/.
In late May, 2004, WHI Hormone Program participants will be mailed information about the WHI-Memory Study (WHIMS) of Estrogen-Alone. Data analysis is currently underway to prepare the publication for of that study’s findings.
14. What is the WHI Extension Study?
The National, Heart, Lung, and Blood Institute has funded a WHI Extension Study to follow all WHI participants through 2010. This study will allow us to collect longer-term data about the effects of stopping hormones (or making other health changes) on women’s health.
If you are a Hormone or Dietary Program participant, you will be given more information about this next study at your last close-out visit, when you will have an opportunity to sign up. If you are an Observational Study participant, you will be given more information and invited to sign up through the mail.
We are inviting all WHI participants, including women in the Hormone Program, to join the Extension Study, no matter which WHI program they joined or which study group they were assigned to.
All participants in the WHI Extension Study will:
  • Fill out a medical history update form once a year and mail it back to the WHI Clinical Coordinating Center in a prepaid envelope.
  • Allow WHI staff to contact them if there are any questions after receiving the forms.
  • Sign a medical release to get more detailed information about health issues that are reported on the medical history update.
Hormone Program participants in the Extension Study will also:
  • Fill out a form about hormone use each year and mail it back in the prepaid envelope along with the medical history update.
  • Have a mammogram each year.
  • Allow WHI staff to obtain a copy of your mammogram report.
WHI Extension Study participants will NOT be asked to:
  • Come to a WHI Clinical Center for any activities.
  • Take any study drugs or other medications, except those prescribed by their health care provider.