Hormonal replacement therapy as a method of prevention and treatment of atherosclerotic diseases in menopausal women

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Estrogen replacement therapy has been found to reduce the incidence of cardio- and cerebrovascular diseases in postmenopausal women. The mechanisms of this vasoprotection are controversial. In recent years, direct vascular actions of estrogens have been proposed in addition to beneficial effects on cardiac risk factors such as hypercholesterolemia. In an attempt to determine the role of direct hormonal influences on human arteries we analyzed the acute vascular responses to 17 beta-estradiol in a series of in vitro and in vivo studies. A dose-dependent estrogen-induced vasorelaxation was found in human coronary arteries in vitro which was more pronounced in women and associated with a significant increase in cyclic AMP and cyclic GMP content. This vascular response could be confirmed in healthy postmenopausal women during a clinical double-blind cross-over study using a quantitative duplex-sonographic approach. Estradiol induced a significant vasodilation and increase of blood flow in femoral arteries, whereas placebo had no effect. As measured by quantitative coronary angiography, high-dose estradiol application was also followed by a significant dilation of epicardial coronary arteries. These direct vascular actions such as vasodilation and increase of blood flow may contribute to the preventive estrogen effects on cardiovascular diseases in postmenopausal women.