[Hormone replacement Up-to-date. The effect of estrogen on vascular function and atherosclerosis]

Not only life span but also life expectancy in all ages are longer in female than male. The incidence of ischemic coronary diseases are drastically increased after menopause and reached almost same severity with that of male after 75 years old. An abundance of epidemiological data confirms this atheroprotective effect of estradiol. The antiatherosclerotic effects of estradiol were thought to be partly attributable to changes in plasma lipid levels (ie, the increase in HDL cholesterol and decrease in LDL cholesterol). However, the contribution of these changes to the total antiatherosclerotic effect of estrogen is only 50%, based on multiple regression analyses. Recently, estrogen receptors have been found in the vascular endothelium and smooth muscle cells, as well as in blood cells such as monocytes. Interest has focused on the role of nitric oxide (NO), because NO has antiatherosclerotic effects. Direct evidence was shown that NO mediates the antiatherosclerotic effect of estrogen. We have found that estrogen acts via an NO-mediated system in vivo and in vitro. However, adverse effects such as thrombosis were reported in estrogen/progesterone replacement therapy in mega clinical trials such as WHI study. We would like to explain and discuss these biphasic effects of estrogen on atherosclerotic diseases including their risk factors such as hyperlipidemia, diabetes mellitus and hypertension.