Frequently Asked Questions about the WHI Estrogen plus Progestin Trial
Issues Specific to Health Care Providers
These questions and answers supplement the 2002 WHI HRT Update sent to all WHI participants in July 2002
- What are the conclusions from the WHI Hormone Program after 5.2 years average follow-up?
- What do these findings mean for my patients who are in the WHI?
- What risks were identified in the E-plus-P trial of the WHI Hormone Program?
- What benefits were identified?
- What other findings were reported?
- Where can I find additional information about these results?
- How does this information apply to my clinical management of patients who are in the WHI Hormone Program (E-Alone and E-plus-P trials)?
- Why did the WHI use 0.625 mg conjugated equine estrogens (CEE) plus 2.5 mg medroxyprogesterone (MPA), when there were other alternatives available?
- How do these results apply to my other patients who are taking or considering hormones?
- What about the beneficial effects of hormones on intermediate outcomes like lipids?
- What is the strength of the evidence provided by the E-Plus-P trial?
- Why did it take so long to release these findings?
- When will there be additional findings from the WHI?
1. What are the conclusions from the WHI Hormone Program after 5.2 years average follow-up?
Answer: From the Estrogen plus Progestin (E-Plus-P) trial, we conclude that taking estrogen plus progestin, as used in this study, does not prevent heart disease and is not beneficial overall. From the Estrogen Alone (E-Alone) trial findings, we conclude that the balnce of risks and benefits for women taking estrogen alone is still uncertain.
2. What do these findings mean for my patients who are in the WHI?
Answer: E-Plus-P participants will continue to have their regular WHI contacts, mammograms and exams. We have asked them to stop their study pills and will inform them of their former study pill assignment. Nothing has changed for participants in the E-Alone trial. They will continue to have their regular WHI contacts, mammograms and exams and they will continue taking their study pills. This information has been superceded by the 2004 Hormone Program Update.
Nothing has changed for participants in the other WHI programs. Women in the Dietary, Calcium and Vitamin D, and Observational Study programs of the WHI will continue to participate as before.
3. What risks were identified in the E-plus-P trial of the WHI Hormone Program?
Answer: Compared to those taking placebo, more women taking active estrogen plus progestin in this study developed breast cancer or experienced cardiovascular events, such as heart attacks, strokes and venous thromboembolism (i.e.,pulmonary emboli and deep vein thromboses).
4. What benefits were identified?
Answer: Women in the E-Plus-P trial who used active hormones had a lower risk of colorectal cancer and a lower risk of fractures.
5. What other findings were reported?
Answer: There were no differences in the number of women who had endometrial cancer or in the number of deaths. When the WHI investigators globally examined the health risks and benefits of estrogen plus progrestin (including coronary heart disease, stroke, pulmonary embolus, breast cancer, endometrial cancer, colorectal cancer, hip fracture, and death from other causes), they found that the balance of risks significantly outweighed the benefits.
6. Where can I find additional information about these results?
Answer: We encourage you to read the paper that is available in print in JAMA (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;288:321-333) and on the JAMA website.
7. How does this information apply to my clinical management of patients who are in the WHI Hormone Program (E-Alone and E-plus-P trials)?
Answer: The findings about breast cancer make it more important than ever that the Hormone Program participants have their annual mammograms, clinical breast examinations, and gynecological examinations. We want to work cooperatively with you as we both continue to follow these participants. Some Hormone Program participants have asked to have their WHI exams done by their own health care providers. If so, we ask your support by encouraging your patients to have their exams and by providing us reports of your findings. E-Alone reports, along with the other follow-up data that we collect, will help us learn about the effects of estrogen alone. E-plus-P reports will help us determine how long the risks (breast cancer, cardiovascular events) and benefits (reduced bone fractures and reduced colorectal cancer) of estrogen plus progestin persist after stopping.
8. Why did the WHI use 0.625 mg conjugated equine estrogens (CEE) plus 2.5 mg medroxyprogesterone (MPA), when there were other alternatives available?
Answer: The WHI investigators chose 0.625 mg CEE and 2.5 mg MPA for the E-plus-P trial because this is the hormone combination used by more than 6 million women in the United States each day. Until the WHI, there were no long-term clinical trials of this hormone combination.
9. How do these results apply to my other patients who are taking or considering hormones?
Answer: Results should be applied as follows:
- Combined postmenopausal hormones, CEE 0.625 mg/day plus MPA 2.5 mg/day, should not be initiated or continued for the primary prevention of coronary heart disease.
- The E-Plus-P trial results may not apply to women taking lower doses of these medications or to other estrogen and progestin formulations.
- For women taking estrogen alone, the overall balance of risks and benefits is still uncertain.
- The E-plus-P trial did not address the short-term risks and benefits of estrogen plus progestin for the treatment of menopausal symptoms.
- Your patient will need your clinical guidance about the risks and benefits of other hormone preparations and hormone alternatives such as bisphosphonates or SERMs.
10. What about the beneficial effects of hormones on intermediate outcomes like lipids?
Answer: The WHI E-plus-P trial findings were based on disease outcomes. Other clinical trials (HERS, ERA) did not show a decrease in cardiac disease events among women with known cardiac disease, despite an increase in HDL-C and decrease in LDL-C. Now the E-plus-P trial adds the finding that while estrogen plus progestin can cause "favorable" changes in lipids, there is no evidence of an associated benefit in reduced CHD.
11. What is the strength of the evidence provided by the E-Plus-P trial?
Answer: Current thought in evidence based medicine recognizes that a randomized clinical trial, like the E-plus-P trial, provides the strongest form of scientific evidence. The WHI E-plus-P trial, involving over 16,000 women across the country, is the largest clinical trial of postmenopausal hormones ever undertaken. Data from multiple clinical trials over the past four years are all consistent with the E-plus-P trial findings. So it now seems indisputable that estrogen plus progestin does not benefit CHD, at least within the first several years of use.
12. Why did it take so long to release these findings?
Answer: We anticipated that women in the E-plus-P trial would need to continue taking their study pills for an average of 8.5 years before we would have answers about the effects of estrogen plus progestin on women's health. The WHI Data and Safety Monitoring Board (DSMB), an independent group of scientific experts, has been reviewing the study data every six months to monitor participant safety in the trial. It was not until its most recent review of the E-plus-P trial data (after an average follow-up of 5.2 years) that the DSMB determined that the overall risks of taking estrogen plus progestin outweigh the benefits. The E-plus-P trial has actually delivered its answers three years ahead of schedule. We do not yet have the answers from the E-Alone trial and await the planned closeout of that trial in three years.
13. When will there be additional findings from the WHI?
Answer: We are continuing to do analyses of data from the E-plus-P trial. As these results become available, we will be providing information to participants via newsletters and website updates and to the medical community via sicentific publications. The remaining WHI programs are proceeding on schedule. At this time, we anticipate findings from the E-Alone trial of the Hormone Program, the Dietary Modification Program, and the Calcium and Vitamin D Program in 2007. Many findings from the WHI Observational Study have already been published, and analyses from this program will continue for many years to come.