[Effect on the venous system and blood coagulation of combined oral estro-progestagen contraceptives and third generation contraceptives]

The steroids contained in oral contraceptives (OCs) influence the venous system and blood coagulation at various levels: the hormones modify the tonus of the venous walls and the coagulability of the blood and may also affect hemodynamics. The arterial endothelium may undergo alterations related to lipid metabolism but this influence is not observed at the level of the venous system. Although the action of sex hormones on the blood vessels has been much studied venous physiopathology remains obscure probably due to its complexity. The tonus of the wall depends on the contractility of the muscles and on the elasticity of the constituent tissues. Estrogen and progesterone receptors have been observed in the venous endothelial cellules. They are more abundant in the legs than in the large veins of the trunk and their density fluctuates with age the menstrual cycle pregnancy and other factors. The progesterone receptors increase under high dose combined OCs. The estrogens appear to favor tonus while progesterone has more of a myorelaxant effect. The hormones affect the musculature by releasing vasoactive substances. The roles of estrogen and progesterone are antagonistic and vascular contractility depends on the balance between the 2 hormones. There is little information available on the action of endogenous estrogens and progesterone on coagulation mechanisms and other properties of the blood. But administration of natural conjugated estrogens to castrated women has not led to observation of major modifications in coagulation factors. Under OCs as during a normal cycle the state of the venous walls is influenced by the estrogen-progestin balance. Most of the research available on the action of OCs on the venous system was conducted on 1st and 2nd generation OCs. The literature on thrombotic risk with OCs is abundant but the conclusions are often discordant. The influence of combined OCs on coagulation mechanisms depends on their metabolic 1st passage through the liver where they affect hepatic synthesis of all the coagulation factors that depend on vitamin K. The effects would tend to increase the coagulability of the blood while diminishing the ability to dissolve clots but some elements such as plasminogen fibrinolysis increase in the opposite direction. Changes in the peripheral circulation under 1st and 2nd generation OCs also tend to be in the direction of increased coagulability. OCs also alter the ability of red blood cells to adapt their shape to the capillaries and suboccluded veins and modify their electrical charge causing changes in blood fluidity. 3rd generation progestins are less androgenous and have greater affinity for progesterone receptors which makes them more like natural progesterone and less weighted with side effects. Reduced estrogen doses in 3rd generation OCs are probably the major element in reduction of venous vascular accidents. The vascular risks of 3rd generation OCs containing smaller estrogen doses and the new progestins will probably be reduced.