Effects of progestogens on haemostasis

Epidemiological data suggested an involvement of the progestogen component in the pathomechanism of venous and arterial diseases during intake of oral contraceptives. The influence of progestogens on haemostasis parameters depend on type and dose of the progestogen, the presence of an estrogen, the route of application, and the duration of use. Treatment of women with progestogen-only preparations caused only minor effects on coagulation and fibrinolysis. Similarly, during hormone replacement therapy with natural estrogens, the additional application of progestogens induced no unfavourable changes on haemostasis. In contrast, the use of ovulation inhibitors resulted in an acceleration of coagulation and fibrinolysis. This is primarily induced by the marked action of ethinylestradiol on hepatic and vascular function. Progestogens with androgenic properties may counteract the estrogen-induced changes in the hepatic synthesis of platelet aggregation and readiness for coagulation. Estrogen and progesterone receptors are localized in endothelial and smooth muscle cells of the vessel wall, but there are differences in the response of veins and arteries to sex steroids. Estrogens and progestogens may influence collagen and elastin synthesis, and the release of vasoactive compounds and of factors controlling fibrinolysis from endothelium. In veins, progestogens may increase distensibility and capacitance resulting in a decreased blood flow. In predisposed women, this may lead to venous stasis and thrombosis. In arteries, progestogens may act as vasoconstrictors, and may enhance vasospasms at sites of injured endothelium which finally may lead to ischemic diseases.