Correspondence
Women's Health Initiative
N Engl J Med 1994; 330:70-71January 6, 1994
- Article
To the Editor:
The National Institutes of Health recently launched the Women's Health Initiative (WHI). Although one of us sits on the WHI Advisory Board, we are commenting not in that capacity, but rather as epidemiologists concerned about the misrepresentation in the lay press of the risks of participation in the WHI1. It is essential that potential benefits as well as risks be clearly communicated to members of the public and their physicians.
The clinical-trial component of the WHI will evaluate the effect of diet and hormone-replacement therapy in preventing coronary heart disease and osteoporosis and will assess the extent of any increased risk of breast cancer. The trial will enroll 55,000 to 60,000 postmenopausal women 50 to 79 years of age. With regard to hormone replacement, women will be assigned randomly to receive one of three treatments: placebo, conjugated equine estrogen (0.625 mg per day), or conjugated estrogen (0.625 mg per day) plus medroxyprogesterone (2.5 mg per day).
The epidemiologic literature provides evidence of an association between treatment with conjugated equine estrogen at a dose of 0.625 mg per day and a reduction of 50 to 60 percent in the rate of hip fractures2 and a reduction of at least 30 percent in mortality from cardiovascular disease3. Thus, the American Heart Association recommends consideration of estrogen-replacement therapy for postmenopausal women, particularly those at increased risk for coronary heart disease and osteoporosis4.
Other studies have shown an increased risk of endometrial cancer associated with postmenopausal estrogen therapy; this increase is mitigated by the use of supplementary progesterone3. In addition, a recent review shows a possible 30 percent increase in the risk of breast cancer after 15 years of estrogen use5. The effect of the addition of medroxyprogesterone on the risks of breast cancer, osteoporosis, and cardiovascular disease is not clear.
On the basis of the available epidemiologic data, the following annual risks and benefits of estrogen replacement alone can be conservatively estimated among the approximately 7500 women in the estrogen-alone group in the WHI trial: increase in annual deaths from breast cancer, 2.1; increase in annual deaths from endometrial cancer, 1.2; decrease in annual deaths from ischemic heart disease, 25.6; and decrease in annual hip fractures, 14.7.
Conversely, administering placebo rather than estrogen to the approximately 10,500 control subjects may result in an annual decrease of approximately 3 deaths each from breast cancer and endometrial cancer, but an annual increase of 26 deaths from coronary heart disease and 11 additional hip fractures. Thus, the probability of fatal illness and hip fracture is likely to be higher among placebo recipients than among participants who receive active treatment.
The existing epidemiologic data indicate that participation in the WHI trial will result in a small net favorable effect attributable to estrogen replacement.
5 ReferencesElaine Eaker, Sc.D.
Marshfield Clinic, Marshfield, WI 54449Robert A. Hahn, Ph.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 303331
Rinzler CA. Estrogen trials and errors. New York Times. September 17, 1993:29.
2
Weiss NS ,Ure CL ,Ballard JH ,Williams AR ,Daling JR . Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 1980;303:1195-1198
Full Text | Web of Science | Medline3
Ernster VL ,Bush TL ,Huggins GR ,Hulka BS ,Kelsey JL ,Schottenfeld D . Benefits and risks of menopausal estrogen and/or progestin hormone use. Prev Med 1988;17:201-223
CrossRef | Web of Science | Medline4
Eaker ED ,Chesebro JH ,Sacks FM ,Wenger NK ,Whisnant JP ,Winston M . Cardiovascular disease in women. Circulation 1993;88:1999-2009
Web of Science | Medline5
Steinberg KK ,Thacker SB ,Smith SJ , et al. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 1991;265:1985-1990
CrossRef | Web of Science | Medline
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