Cardiovascular risk factors impair endothelium-mediated vasodilatation. Endothelium-dependent vasorelaxation mediated by nitric oxide differs with gender and is modulated by chronic estrogen therapy. Declining levels of circulating estrogen causes progressive changes of endothelial function; these changes may be related to the loss of estrogen receptors. They physiologic studies of estrogen therapy in premenopausal women undergoing surgical ovariectomy demonstrate that estrogen replacement could restore vascular reactivity to premenopausal levels. It is believed that estrogen exerts it beneficial effects on the cardiovascular system in larger part through augmenting the release of nitric oxide from the endothelium.