| Abstract: | This article examines the effect of dose level of both estrogens and progestins as factors in the cardiovascular risk of oral contraceptives (OCs), and also examines the roles of blood pressure, coagulation factors, and lipid metabolism. A large number of epidemiologic studies have demonstrated the connection between OC use and thromboembolic disease since the 1st such study appeared 2 decades ago, but the early studies concerned formulations with much higher estrogen doses than those currently used, taken by women who were older and more likely to smoke than at present. Very few epidemiologic studies dealing with the newer formulations are yet available. It is easier to analyze the dose-response relations for the progestins than for the estrogens given that the 2 estrogens primarily used, ethinyl estradiol (EE) and mestranol, were used for a series of progestins at different doses to examine their effects with a constant dose of estrogen. Nevertheless, the epidemiologic studies show increased risks of thrombotic accidents and a dose-response relation for both the estrogen and progestin components. It is likely that different mechanisms are responsible. The effects of OCs on blood pressure have been monitored carefully since the 1st observations of hypertension in OC users. Blood pressure elevations are usually attributed to the estrogen, but there is evidence of a progestin role as well. Some studies have found differences in blood pressure at the same estrogen dose but with different progestin content. It is very likely that blood pressure undergoes physiologic variations depending on hormonal fluctuations. The mechanism by which some OC users develop hypertension is poorly understood, but it may be related to changes in the renin-angiotensin-aldosterone system. Androgenic progestins accentuate sodium retention, which may play a role. Researchers have shown that the lipid profiles of women at different stages of life are different, whether or not they use OCs. Among young women HDL cholesterol levels decline and LDL levels increase among users relative to nonusers of OCs. On the other hand, old women receiving estrogen substitution therapy tend to have more favorable lipid profiles than do women of the same age not receiving estrogen. Coagulation factors, especially factors VII and fibrinogen, have been established as important cardiovascular risk factors in men. Some studies have shown the levels of factors VII and fibrinogen to be elevated in OC users. These procoagulant alterations are also observed in women receiving estrogen substitution, but unlike OC users such women appear to be protected by age-related increases in the level of antithrombin III. Smoking is an important influence on the fibrinogen level, which probably explains part of the increased risk of myocardial infarct among OC users. |
