Aging, menopause, and free radicals.

As women undergo menopause, circulating concentrations of estrogen decrease. The relative estrogen deprivation in postmenopausal women is associated with physiological changes and increased risk of several diseases, including cardiovascular disease. Studies in animals have shown that exogenous estrogen inhibits atherosclerosis, the underlying cause of cardiovascular disease. Ongoing clinical trials will soon provide data for the effect of exogenous estrogen on cardiovascular disease in postmenopausal women. Estrogen has a number of effects that could influence atherogenesis and cardiovascular disease. Estrogens have favorable effects on lipoproteins, but such effects can only account for part of the protection from cardiovascular disease that appears to be conferred by estrogen. Evidence suggests that estrogens can have both prooxidant and antioxidant effects. However, the available evidence suggests that in vivo physiological concentrations of estrogen may have a modest antioxidant activity, and prooxidant activity is unlikely. The antioxidant activity of estrogens and inhibition by estrogens of cellular processes that are thought to promote atherosclerosis are likely to be additional mechanism(s) by which estrogen inhibits atherosclerosis and cardiovascular disease, but more work is needed. Studies of some effects of estrogens on atherogenic processes in isolated cells need to be extended to the whole animal. The influence of estrogen receptors on inhibition of atherosclerosis by estrogen needs to be clarified. Future studies should be designed to investigate separately the estrogenic and antioxidant activities of estrogens and estrogen analogs. Investigations of the antioxidant activities of estrogens should include careful consideration of the interaction of estrogens with endogenous antioxidants and fatty acid saturation, and more attention should be paid to the potential for estrogens to inhibit intraarterial oxidation.