Ovarian sex steroids and atherosclerosis.

Abstract

Estrogens have been found to protect against atherosclerosis in a variety of animal models, and these antiatherogenic properties have been confirmed by epidemiological and clinical studies in women as well. Since the estrogen-induced changes of plasma lipid and lipoprotein levels do not fully account for the prevention of atherosclerosis, additional effects must be assumed. Experimental studies suggest various direct vascular actions. Estrogens enhance the endothelial degradation of low-density lipoprotein cholesterol, and preliminary data indicate antioxidative actions on low-density lipoprotein particles in macrophages. They suppress intimal proliferation and extracellular matrix production in the arterial wall and induce marked vasodilatation in systemic and coronary arteries. Adverse effects on hemostatic factors described with high doses and synthetic compounds are not evident during hormonal replacement in postmenopausal women, in whom an estradiol-induced inhibition of platelet aggregation may even have beneficial clinical effects. The role of progesterone and other progestogens in the progression of atherosclerosis is controversial. Despite a partial antagonism to estrogen-induced changes of plasma lipids, their addition to estrogens does not alter the anti-atherosclerotic properties, at least in animal experiments. The direct vascular actions of progestogens-although not as well documented-seem to be less pronounced than those of estrogens. The experimental data indicate that direct vascular effects play an important role in the antiatherogenic properties of ovarian sex steroids. However, the underlying cellular and molecular mechanisms remain largely unknown.