Abstract

PIP: Estrogen-progestogen oral contraceptives (OCs) have been shown in numerous studies to increase the risk of venous thromboembolic disease, myocardial infarction, and thrombotic stroke. Until recently, it has been assumed that the increased risk of vascular disease was attributable to the estrogen component of the OC. However, available evidence suggests that venous thromboembolic complications are determined by the estrogen component, whereas arterial complications may be due to both the estrogenic and progestogenic components. The authors investigated the comparative effect of different low-dose combined OCs on the hemostatic system. The effects of ethinyl estradiol on coagulation fibrinolysis and platelet function were found to be dose-related: 50 mcg of ethinyl estradiol produced significantly greater changes than 30 mcg, and the effects of 30 mcg ethinyl estradiol were modified by the progestogen used. Further studies compared 50 mcg and 30 mcg estrogen contraceptives and a triphasic formulation containing levonorgestrel. Again, changes in coagulation activity and fibrinolysis were related to the dose of estrogen and progestogen. The absence of significant changes in antithrombin III with monophasic and triphasic levonorgestrel suggests that levonorgestrel counteracts the action of estrogen in depressing this coagulation inhibitor. The fewest changes in coagulation factors and inhibitors occurred among women taking low-dose estrogen combined with levonorgestrel, indicating that progestogen used in combination modifies the estrogenic effects on the coagulation system. Current research is aimed at finding estrogen-progestogen combinations that produce fewer changes in the hemostatic system and in other metabolic processes. The combination of low-dose ethinyl estradiol with levonorgestrel in a triphasic preparation should reduce the risk of vascular complications and contribute to the safety of OCs.