Hemostatic effects of third- and second-generation oral contraceptives: absence of a causal mechanism for a difference in risk of venous thromboembolism.

Some observational studies have found a difference in the risk of nonfatal venous thromboembolism (VTE) with low-dose, oral contraceptives (OCs) containing desogestrel (DSG) or gestodene (GSD) and those containing levonorgestrel (LNG). However, this does not agree with current pathophysiological concepts. This review compares all 17 comparative studies on the hemostatic effects of DSG/GSD- and LNG- or norgestimate (NGM)-containing OCs, and comments on two recent cross-sectional studies on the effects of third- and second-generation OCs on activated protein C (APC) sensitivity. In the comparative studies, the only difference in hemostatic parameters between DSG/GSD- and LNG- or NGM-containing OC users was a tendency towards higher factor VII (FVII) levels with DSG/GSD OCs. Differential effects on APC sensitivity were observed with the endogenous thrombin generation potential (ETP) assay, but not with the classical APC resistance test. FVII is not a risk marker for VTE, but is affected by dietary fat, estrogens and androgens and may interfere with the ETP assay. As no differences in established VTE risk markers were observed, there is no plausible reason for a differential risk of VTE with DSG/GSD- and LNG-containing OCs. In fact, the lack of differences with regard to established risk markers of VTE gives further support to the findings of the most recent epidemiological studies, which have not found any difference in the risk of VTE between third- and second-generation OCs.