[Metabolic impact of current estrogen-progestins and cardiovascular consequences]

Abstract

In recent years, reduction of estrogen and progestogen dosages and use of new progestogens with less androgenic activity (desogestrel-gestodene-norgestimate) have apparently allowed combined oral contraceptives (OCs) to be associated with less frequent undesirable vascular effects. From an epidemiologic viewpoint, the atherogenic impact of new low-dose OCs is less marked, including in users over 40 years of age, but thromboembolic effects still persist--though at a lower level than with standard-dose products. From a metabolic viewpoint, the adverse effects of the progestogens contained in current OCs on the lipoprotein profile and their atherogenic effect on the vessel wall seem effectively counterbalanced by the estrogen content of these new OCs. However, the progestin content seems still responsible for a low level of chronic insulin resistance, which might be related to vascular alterations potentially linked to syndrome-X. In conclusion, reduced metabolic effects of new low-dose OCs appear to decrease their atherogenic risk. However, thrombotic effects dose-related to the estrogen component of OCs are still persisting and seem less easily suppressible.

PIP: The use of high-dose contraceptives with estrogen-progestogen components was associated with excess morbidity and mortality owing to cardiovascular insults. Estrogen contributed to the coagulation effects, and the androgenic effects of progestogen influenced glucose and lipid metabolism, resulting in arterial and venous thromboembolitic incidents. However, with the new generation of low-dose ethinyl estradiol (EE) and less androgenic progestogen (desogestrel, gestodene, and norgestimate) preparations a drastic reduction of thromboembolitic complications ensued. The diminished progestogen in triphasic preparations containing EE and levonorgestrel (LNG), a 1st generation progestogen, affect the lipoprotein profile much less: the LDL cholesterol is lightly increased, the HDL cholesterol is almost unchanged, but the HDL2 cholesterol is always significantly reduced. In low-dose EE and slightly androgenic (desogestrel, gestodene, norgestimate) or nonandrogenic (cyproterone acetate) progestogen- containing OCs the HDL in unchanged or slightly elevated, the IDL and LDL fractions are unchanged or slightly reduced despite a moderate increase of triglycerides and VLDL particles probably producing little atherogenic effects. The effects on carbohydrate metabolism of low-dose LNG are minor regarding glucose tolerance, and it is even more clearly so with the low-dose new generation OCs containing gestodene and desogestrel. The progestin content seems still responsible for a low level of chronic insulin resistance, which might be related to vascular alterations potentially linked to syndrome-X. In conclusion, the reduced metabolic effects of new low-dose OCs appear to decrease their atherogenic risk, but the thrombotic effects dose-related to the estrogen component of OCs still persist, and these negative effects should not be underestimated.