[Vascular effects of gestagens--biochemistry versus epidemiology]

The available epidemiologic data indicate that the sequential addition of progestogens enhances the protective effect of estrogens on the cardiovascular risk. A considerable decrease in LDL-cholesterol is also observed during use of progestogens with androgenic properties. The estrogen-dependent reduction of LDL oxidation is not impaired by progestogens. While estrogens inhibit the endothelial synthesis of adhesion molecules, the activation of monocytes and platelets and the proliferation and migration of smooth muscle cells, the effect of progestogens is rarely investigated. A vasoconstrictory effect of progestogens which may attenuate the estrogen-induced dilation of arteries, was not observed in all clinical investigations. It is presumably based on a reduction of estrogen-stimulated release of nitric oxide by progestogens. In most animal experiments, a progestogen-induced enhancement of contractility of arteries was measured, too. A relaxing effect of progesterone was found in in vitro-experiments, while the results on endothelium-independent effects of synthetic progestogens were contradictory. The sex steroids influence the structure of the vessel wall, whereby the elasticity of arteries is enhanced by estrogens and reduced by progestogens. Oral contraceptives may increase the distensibility of veins which correlates with the hormonal potency of the progestogen. During hormone replacement therapy, venous distensibility is also increased which is mainly due to the action of the estrogen. In vitro experiments with veins revealed a dilatory effect of progestogens. With regard to possible unfavourable effects of progestogens on the vessel wall it is recommended to use the additional progestogen at the minimal effective dose necessary for prevention of endometrial hyperplasia.