Frequently Asked Questions about the WHI Estrogen plus Progestin Trial

Issues of Interest to All WHI Participants

These questions and answers supplement the 2002 WHI HRT Update sent to all WHI participants in July 2002.
  1. Why have we asked women in the estrogen plus progestin study to stop study pills at this time?
  2. What were the main findings in the study on estrogen plus progestin?
  3. What are the conclusions from these findings?
  4. What were the actual hormones that women in the estrogen plus progestin study were taking?
  5. What are the increased risks for women taking estrogen plus progestin?
  6. What are the reduced risks for women taking estrogen plus progestin?
  7. When did the increased risk of breast cancer become apparent for women taking estrogen plus progestin compared to women taking placebo pills?
  8. Is there an increased risk of breast cancer in women taking estrogen alone?
  9. How were WHI participants notified of these results?
  10. Should I discuss this new information with my health care provider?
  11. I am taking prescription hormones, what should I do?
  12. I heard some news about the HERS study on hormones and heart disease. Is that the same study as the WHI?
  13. Do you have recommendations about other hormone alternatives (lower-dose estrogens, micronized progesterone, natural hormones)?
  14. Does this new information apply to Selective Estrogen Receptor Modulators (SERMS) or phytoestrogens?
  15. What is the Data Safety and Monitoring Board?
  16. Can I withdraw from the WHI?

1. Why have we asked women in the estrogen plus progestin study to stop study pills at this time?
Answer: In its most recent review of the study data, the WHI Data and Safety Monitoring Board saw an increased risk of breast cancer in women taking estrogen plus progestin. The Board also saw that the previously identified risks for heart attacks, strokes and blood clots to the lungs and legs had persisted. Therefore, in the judgment of the Board, the overall risks outweighed the benefits of taking estrogen plus progestin.
2. What were the main findings in the study on estrogen plus progestin?
Answer: The main findings show that compared to women taking placebo pills:
  • The number of women who developed breast cancer was higher in women taking estrogen plus progestin.
  • The numbers of women who developed heart attacks, strokes, or blood clots in the lungs and legs were higher in women taking estrogen plus progestin.
  • The numbers of women who had hip and other fractures or colorectal cancer were lower in women taking estrogen plus progestin.
  • There were no differences in the number of women who had endometrial cancer (cancer of the lining of the uterus) or in the number of deaths.
The answer to Question #6 includes information on the increased benefits for hip fractures and colon cancers. The answer to Question #7 includes information on the increased risks for breast cancers, heart attacks, and strokes.
3. What are the conclusions from these findings?
Answer: The main conclusions are:
  • The estrogen plus progestin combination studied in WHI does not prevent heart disease.
  • For women taking this estrogen plus progestin combination, the risks (increased breast cancer, heart attacks, strokes, and blood clots in the lungs and legs) outweigh the benefits (fewer hip fractures and colon cancers).
The estrogen plus progestin study participants are women who had a uterus when they joined the WHI Hormone Program. There is another Hormone Program study on estrogen alone that includes women who had a hysterectomy before they joined. We do not know how the results from the WHI study of estrogen plus progestin relate to the study of estrogen alone. We do know that the DSMB has recommended that the study of estrogen alone continue. In that study the balance of risks and benefits are still being evaluated. See the section on Issues Specific to Women in the Estrogen Alone Study.
4. What were the actual hormones that women in the estrogen plus progestin study were taking?
Answer: Women who were randomized to receive active hormones were taking conjugated equine estrogens 0.625 mg each day and medroxyprogesterone acetate 2.5 mg each day.
This is the most commonly prescribed postmenopausal hormone therapy in the United States for women who have a uterus (used each day by more than six million women).
5. What are the increased risks for women taking estrogen plus progestin?
Answer: For every 10,000 women taking estrogen plus progestin pills:
  • 38 developed breast cancer each year compared to 30 breast cancers for every 10,000 women taking placebo pills each year.
  • 37 developed a heart attack compared to 30 out of every 10,000 women taking placebo pills.
  • 29 had a stroke each year, compared to 21 out of every 10,000 women taking placebo pills.
  • 34 had blood clots in the lungs or legs, compared to 16 women out of every 10,000 women taking placebo pills.
6. What are the reduced risks for women taking estrogen plus progestin?
Answer: For every 10,000 women taking estrogen plus progestin pills:
  • 10 had a hip fracture each year, compared to 15 out of every 10,000 women taking placebo pills each year.
  • 10 developed colon cancer each year, compared to 16 out of every 10,000 women taking placebo pills.
7. When did the increased risk of breast cancer become apparent for women taking estrogen plus progestin compared to women taking placebo pills?
Answer: There was no difference in the development of breast cancer during the first 4 years between women taking estrogen plus progestin and those taking placebo pills. After that time, the numbers began to increase. After an average of 5.2 years, there was an increased risk of breast cancer in women taking estrogen plus progestin compared to those taking placebo pills.
8. Is there an increased risk of breast cancer in women taking estrogen alone?
Answer: There is no evidence of an increased risk for breast cancer in women taking active estrogen alone, compared to those taking placebo pills, even after an average of 5.2 years. We do not know whether the long-term effects will differ. The Data Safety and Monitoring Board will continue to review participants’ health data every 6 months.
This information has been superceded by the 2004 Hormone Program Update.
9. How were WHI participants notified of these results?
Answer: Two different letters were mailed to WHI participants in early July 2002--one for women in the estrogen plus progestin study and one for those in the study of estrogen alone. Another letter will be mailed later in July to all WHI participants who are not in the Hormone Program. Those women who are only in the WHI Diet trial, or the Diet trial and calcium vitamin D trial, only and those women who are in the Observational Study will receive these letters.
Some local WHI clinics may also have sent letters to participants enrolled at their clinic.
10. Should I discuss this new information with my health care provider?
Answer: We encourage you to share this information with your health care provider. Your local WHI clinic can give you information to take to your health care provider. Your health care provider may also review the scientific article on these findings in The Journal of the American Medical Association. Your health care provider may also call the local WHI clinic and speak with the Principal Investigator or Clinic Practitioner about this information.
11. I am taking prescription hormones, what should I do?
Answer: We recommend that you talk with your health care provider about your individual health risk profile and the hormones you are currently taking.
12. I heard some news about the HERS study on hormones and heart disease. Is that the same study as the WHI?
Answer: No. HERS was a different trial that focused only on women with heart disease. Women in the WHI estrogen plus progestin study were generally healthy, and most of them did not have heart disease when they joined. Both studies found that estrogen plus progestin did not reduce a woman's risk of heart attacks. Both studies also found that estrogen plus progestin increased a woman's risk of having a blood clot.
13. Do you have recommendations about other hormone alternatives (lower-dose estrogens, micronized progesterone, natural hormones)?
Answer: We cannot make specific recommendations about other hormone medications, such as different estrogens or progestins. We also cannot make recommendations about hormones women take in lower dosages or in different ways, such as patches instead of pills.
Without scientific clinical trial data, one cannot assume that alternative estrogen plus progestin treatments are any safer than those studied in WHI.
14. Does this new information apply to Selective Estrogen Receptor Modulators (SERMS) or phytoestrogens?
Answer: These preparations were not studied in the WHI Hormone Program, and therefore, we cannot make any conclusions about the risks or benefits of SERMs, such as raloxifene (Evista®) or tamoxifen (Nolvadex®) or phytoestrogens.
15. What is the Data Safety and Monitoring Board?
Answer: The Data and Safety Monitoring Board (DSMB) is an independent board of medical researchers that has responsibilities for ensuring the safety of participants and the proper conduct of the study. The DSMB reviews all of the study data every 6 months. The Board includes twelve outstanding medical researchers with expertise in aging, behavioral science, cancer, cardiology, ethics, gynecology, nutrition, osteoporosis, statistics, and women’s health. The Board reports directly to the Director of the National Heart, Lung, and Blood Institute (NHLBI), which funds the WHI program.
Each WHI Clinical Center also has a separate review board called an Institutional Review Board (IRB). The local IRB is responsible for making sure that participants are kept fully informed about the study and that their safety is protected.
16. Can I withdraw from the WHI?
Answer: As with any research study, you can withdraw at any time.