So You Took Hormones, Now What?
Abstract & Commentary
By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky;Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips reports no financial relationship to this field of study.
Synopsis: For those women who were randomized to estrogen plus progesterone in the Women's Health Initiative Trial, the increased risk of breast cancer has persisted since stopping the replacement therapy, but the increased risk of cardiovascular events has returned to that of the placebo group.
Source: Gerardo Heiss G, et al. JAMA. 2008;299(9):1036-1045.
What has happened to the women in the Women's Health Initiative (WHI) study who were randomized to hormone replacement therapy (HRT) since the trial was prematurely terminated? This paper reports the results of continued observation of 15,730 of the original 16,608 women in the WHI trial after HRT was stopped. In brief, treatment in the WHI study consisted of conjugated equine estrogens plus medroxyprogesterone acetate (Prempro), or matching placebo. Standardized information was collected on symptoms, adverse events, adherence to study pills, and potential trial clinical outcomes twice yearly during the intervention phase, which ended July 7, 2002. After the abrupt termination of the treatment part of the study, the investigators continued to follow the women enrolled until March 31, 2005. Follow-up included continued collection of the measures included in the treatment phase, as well as annual mammography. The women in the placebo and HRT groups were not different in baseline characteristics. They had a mean age of 63 years.
After about 3 years of follow-up, the risk of cardiovascular events in the two groups was no longer different, nor were the risks of deep vein thrombosis or pulmonary embolism. However, the "all cancer" risk was higher for the HRT group, driven primarily by an increased risk of invasive breast cancer in the HRT group. The lower risk of colorectal cancer that had been observed during the treatment phase disappeared during the observation period, as did the slightly reduced risk of fractures. There was a statistically insignificant increase in all-cause mortality in the HRT group during the period of follow-up.
Commentary
We all remember the furor that resulted when the WHI trial of HRT was stopped in the summer of 2002 after only 5.6 years. The study was terminated because of an increased risk of invasive breast cancer and the failure to demonstrate an overall health benefit, in addition to increased risks of cardiovascular disease (CVD), coronary heart disease (CHD), stroke, and venous thromboembolism in those who were taking HRT.1 Since that report, guidelines for menopausal hormone therapy have changed2,3 and use of hormone replacement therapy has declined markedly.
This report gives a glimpse into the future of women who have used hormone replacement therapy, and suggests strategies to minimize ongoing risk. Women can be reassured that risk of cardiovascular disease and death (the leading cause of death for women and men in the US) quickly returns to baseline after cessation of hormone use. On the other hand, the increased risk of malignancy persists, at least for 3 years. Annual mammography and avoidance of other risks for malignancy (smoking, obesity) are especially important for those who have taken or who continue to take hormone replacement.
References
1. Rossouw JE, et al. JAMA. 2002;288(3):321-333.
2. American College of Obstetricians and Gynecologists (ACOG) Task Force on Hormone Therapy. Hormone therapy. Obstet Gynecol. 2004;104(4)(4 suppl):1S-4S.
3. US Preventive Services Task Force. Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the US Preventive Services Task Force. Ann Intern Med. 2005;142(10):855-860.
4. Hersh AL, Stefanick ML, Stafford RS. JAMA. 2004;291(1):47-53.
For those women who were randomized to estrogen plus progesterone in the Women's Health Initiative Trial, the increased risk of breast cancer has persisted since stopping the replacement therapy, but the increased risk of cardiovascular events has returned to that of the placebo group.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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