Sex hormones and atherosclerosis in postmenopausal women

Cardiovascular disease is the leading cause of death in women in the United States and in the entire world. Both incidence and prevalence of cardiovascular disease increase significantly after menopause, indicating changes in the sex hormone milieu may be an important contributor. More than 80 observational epidemiologic studies have showed a significant reduction in cardiovascular disease risk and extent of atherosclerosis with postmenopausal hormone therapy. A number of in vitro studies and studies using animal models have demonstrated the direct and indirect cardiovascular effect of estrogen. However, only a handful of studies have evaluated the association of circulating estrogens and other sex hormone levels to cardiovascular disease and risk factors of cardiovascular disease in women. Literatures relating sex hormones and cardiovascular disease consistently demonstrated an inverse association between total testosterone, sex hormone binding globulin and cardiovascular disease/atherosclerosis. However, none of the studies showed any association with estrogens. The most plausible explanation for this could be measurement error in estrogen. Given the significant within subject variation of estrogen levels in postmenopausal women, one single determination of estrogen may not be enough to characterize estrogen. We used data from Estrogen in the Prevention of Atherosclerosis Trial (EPAT) where estrogens, androgens and sex hormone binding globulin were measured multiple times over two years.;Atherosclerosis was measured by intima-media thickness of the common carotid artery using B-mode ultrasound at the beginning and every six months during the follow-up of the study. Markers of inflammation such as C-reactive protein, intercellular adhesion molecule-1 and homocysteine were also measured every six months. We report a significant inverse association between estrogens, total testosterone and sex hormone binding globulin with atherosclerosis progression. We also report that estrogens were significantly beneficially associated with HDL- and LDL-cholesterol, markers of inflammation and homocysteine. We also demonstrated that the inverse association between estrogens and atherosclerosis progression was partially explained by their beneficial association with serum cholesterols. These results may help understand the cardiovascular impact of estrogens and other sex hormones in postmenopausal. Thereby reduce the bulk of morbidity and mortality of this high risk population.