Postmenopausal hormones and heart disease.

Multiple observational studies have reported that postmenopausal women who use estrogen have a lower rate of coronary heart disease (CHD) events than women who do not use estrogen (1). Meta-analyses of these epidemiologic findings suggest a 35% to 50% reduction in risk of coronary disease among women using estrogen compared to nonusers (2,3). These findings are supported by plausible biologic mechanisms including a beneficial effect of estrogen therapy on low-density lipoprotein and high-density lipoprotein cholesterol (4), improved endothelial function (5) and less progression of atherosclerosis in animals (6). Thus, it was very surprising when the results of the first large trial of the effect of postmenopausal hormone therapy on risk for coronary events showed no benefit of treatment. The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized, blinded, clinical trial among 2,763 postmenopausal women with documented coronary disease and a uterus; they were randomly assigned to receive daily conjugated estrogen plus medroxyprogesterone acetate or placebo. After an average of 4.1 years of follow-up, there was no difference between the groups in the primary composite outcome of nonfatal myocardial infarction (MI) and coronary death or any of several secondary cardiovascular outcomes (7). Even more surprisingly, HERS investigators found that women assigned to estrogen plus pro-