The Effect of Hormonal Contraceptives on Metabolism

Abstract

Hormonal contraception (HC) is used worldwide to control reproduction. Because used in healthy women, occurrence of HC-associated side effects or complications is of concern and hardly tolerated. The risk of cardiovascular disease is very low in young women, but also at this age, a prolonged exposition to cardiovascular risk factors could accelerate atherosclerosis and lead to an earlier manifestation of cardiovascular events. The metabolic changes induced by the synthetic steroids used in contraception, such as changes in lipoprotein, carbohydrate metabolism, and blood pressure, can be considered potential mechanisms capable to influence lifetime occurrence of cardiovascular disease. Ethinyl estradiol (EE) exerts a stronger effect than estradiol (E2) on hepatic metabolism and protein synthesis. EE doesn’t show any major effect on carbohydrate metabolism and induces lipoprotein modifications considered to be protective for the development of atherosclerosis. Androgenic progestins, testosterone-related, decrease insulin sensitivity, increase glucose response to an OGTT, and counteract the effect of estrogens on lipoprotein metabolism, inducing a pro-atherosclerotic shift. When androgenic progestins are substituted by non-androgenic or antiandrogenic progestins, the effect of HC on carbohydrate metabolism is neutral, and the observed lipoprotein profile is likely protective against atherosclerosis. In contrast to E, EE increases blood pressure. Drospirenone, an antiandrogenic progestin, related to spironolactone, with anti-mineralocorticoid activity, may counteract the rise in blood pressure induced by EE. In the absence of a clear epidemiological evidence, it seems wise to consider HC-induced modification of risk factors as predictive of future cardiovascular disease.