Estrogen and Endothelial Function

Although observational studies have shown that estrogen can protect women against cardiovascular diseases (CVD), the underlying mechanisms are not fully clarified. Endothelium plays a pivotal role in the control of vascular function and structure; endothelial dysfunction, characterized by reduced or absent nitric oxide (NO) bioavailability linked and/or due to the production of cyclooxygenase-dependent endothelial-derived contracting factors (EDCFs), mainly represented by oxygen free radicals, is now viewed as an important mechanism causing atherothrombosis. Data in humans indicate that endogenous estrogen plays a protective role on endothelial function. Thus premenopausal women are protected against the adverse effect of hypercholesterolemia, with age-related impairment of endothelial function occurring only after the menopause in normotensive women and mainly after the menopause in hypertensive women. Moreover endogenous estrogen deprivation selectively impairs endothelial function in normotensive women. There is also evidence that exogenous estrogen can improve endothelial function in postmenopausal women. Thus acute intraarterial or intravenous infusion of estrogen potentiates endothelium-dependent vasodilation both in coronary circulation and the forearm. Estrogen replacement therapy (ERT) seems to improve endothelial function both in coronary arteries of postmenopausal women with coronary atherosclerosis and in brachial arteries of postmenopausal women with mild hypercholesterolemia. Although short-term ERT did not improve endothelial function in the forearm of perimenopausal women and in postmenopausal women with various cardiovascular risk factors, 3-month ERT restored endothelial function in ovariectomized women.