Aging, menopause, and free radicals

As women undergo menopause, circulating concentrations of estrogen decrease . The relative estrogen deprivation in postmenopausal women is associated w ith physiological changes and increased risk of several diseases, including cardiovascular disease. Studies in animals have shown that exogenous estro gen inhibits atherosclerosis, the underlying cause of cardiovascular diseas e. Ongoing clinical trials will soon provide data for the effect of exogeno us 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 fi om cardiovascular disease t hat appears to be conferred by estrogen. Evidence suggests that estrogens c an have both prooxidant and antioxidant effects. However, the available evi dence suggests that in vivo physiological concentrations of estrogen may ha ve a modest antioxidant activity, and prooxidant activity is unlikely. The antioxidant activity of estrogens and inhibition by estrogens of cellular p rocesses that are thought to promote atherosclerosis are likely to be addit ional mechanism(s) by which estrogen inhibits atherosclerosis and cardiovas cular disease, but more work is needed. Studies of some effects of estrogen s on atherogenic processes in isolated cells need to be extended to the who le animal. The influence of estrogen receptors on inhibition of atheroscler osis by estrogen needs to be clarified. Future studies should be designed t o investigate separately the estrogenic and antioxidant activities of estro gens and estrogen analogs. Investigations of the antioxidant activities of estrogens should include careful consideration of the interaction of estrog ens with endogenous antioxidants and fatty acid saturation, and move attent ion should be paid to the potential for estrogens to inhibit intraarterial oxidation.