Postmenopausal Estrogen Therapy and Cardiovascular Disease

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Abstract
The effect of postmenopausal estrogen therapy on the risk of cardiovascular disease remains controversial. Our 1985 report in the Journal, based on four years of follow-up, suggested that estrogen therapy reduced the risk of coronary heart disease, but a report published simultaneously from the Framingham Study suggested that the risk was increased. In addition, studies of the effect of estrogens on stroke have yielded conflicting results. We followed 48,470 postmenopausal women, 30 to 63 years old, who were participants in the Nurses' Health Study and who did not have a history of cancer or cardiovascular disease at base line. During up to 10 years of follow-up (337,854 person-years), we documented 224 strokes, 405 cases of major coronary disease (nonfatal myocardial infarctions or deaths from coronary causes), and 1263 deaths from all causes. After adjustment for age and other risk factors, the overall relative risk of major coronary disease in women currently taking estrogen was 0.56 (95 percent confidence interval, 0.40 to 0.80); the risk was significantly reduced among women with either natural or surgical menopause. We observed no effect of the duration of estrogen use independent of age. The findings were similar in analyses limited to women who had recently visited their physicians (relative risk, 0.45; 95 percent confidence interval, 0.31 to 0.66) and in a low-risk group that excluded women reporting current cigarette smoking, diabetes, hypertension, hypercholesterolemia, or a Quetelet index above the 90th percentile (relative risk, 0.53; 95 percent confidence interval, 0.31 to 0.91). The relative risk for current and former users of estrogen as compared with those who had never used it was 0.89 (95 percent confidence interval, 0.78 to 1.00) for total mortality and 0.72 (95 percent confidence interval, 0.55 to 0.95) for mortality from cardiovascular disease. The relative risk of stroke when current users were compared with those who had never used estrogen was 0.97 (95 percent confidence interval, 0.65 to 1.45), with no marked differences according to type of stroke. Current estrogen use is associated with a reduction in the incidence of coronary heart disease as well as in mortality from cardiovascular disease, but it is not associated with any change in the risk of stroke. (N Engl J Med 1991; 325:756–62.)