Influence of the menstrual cycle on the timing of acute coronary events in premenopausal women

Abstract

During their reproductive years, women have a low incidence of coronary artery disease (1,2), which increases markedly 10 to 15 years after menopause (3). It has long been hypothesized that this increased risk is at least in part due to the absence of female hormones, in particular, 17 -estradiol (4). This hypothesis was supported by data from epidemiological studies, which suggested that hormone replacement therapy would protect postmenopausal women from coronary artery disease (5– 8). However, recent placebo-controlled trials designed to test the cardioprotective effects of a regimen of estrogens plus progestin have found no reduction in cardiovascular events or progression of angiographic lesions (9 –12). Nevertheless, acute administration of 17 -estradiol affects the vasculature by modulating the nitric oxide–Larginine pathway (13,14), and improves endothelial function (15) and prolongs the time to ST-segment depression and exercise time, in postmenopausal women with coronary artery disease (16). These data suggest that the acute effects of 17 -estradiol could subside rapidly when levels are low during menses. Therefore, we sought to determine whether premenopausal women would be at greater risk of developing an acute coronary event when blood levels of 17 -estradiol levels are low during the menstrual cycle.