Abstract
Coronary heart disease (CHD) is the leading cause of death in both pre- and postmenopausal women in Western societies. Both natural and surgical menopause are associated with increased risk of CHD (1), although estrogen replacement therapy (ERT) reduces the risk of CHD by about 50% in postmenopausal women (2–4) and the amount of atherosclerosis by about 50% in animal models (5–8). Even though there is overwhelming evidence that estrogen monotherapy markedly reduces the risk of CHD in postmenopausal women, the effects of estrogen/progestin regimens on CHD risk are less clear. A progestin is added to the ERT regimen to reduce the risk of endometrial cancer, and this may detract from estrogen’s beneficial effects. For example, numerous observational studies as well as meta-analyses (2,4) have concluded that ERT reduces risk of CHD. Reports from the Nurses Health Study (9) found similar reductions in CHD risk with ERT and combined estrogen/progestin treatment (HRT); however, a report of the first randomized, blinded, secondary prevention trial the Heart and Estrogen/progestin Replacement Study (HERS)—found no significant differences between CHD events in the placebo group compared with a group treated with combined, continuous estrogen/progestin (conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) (10).
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