Previous reports and reviews indicate differences in effects of second and third generation combined oral contraceptives (COCs) on haemostasis variables. This review analyses directly comparative studies on such effects. From the literature, 17 longitudinal comparative studies with parallel groups were retrieved, containing data on comparisons between COCs containing levonorgestrel (second generation COCs) and COCs containing desogestrel, gestodene or norgestimate (third generation COCs) with 30-35 mg ethinylestradiol. Six or more comparisons were available only for fibrinogen, platelet count, antithrombin III, factor VII, factor VIII and factor X. The comparisons reveal a consistently larger increase in factor VII with the third generation COCs compared to the second generation COCs. The effects on factor VII do not coincide in these comparative studies with effects on factor X and prothrombin, rendering a specific sensitivity of the vitamin K-dependent mechanisms for progestogens unlikely. Fibrinogen effects tend to be different for the different progestogens, suggesting a progestogen-specific dependence. Trends in antithrombin III are towards more reduction for the third generation COCs, but the effects are very minor. The effects on factor V suggest a possible progestogen specificity, which may be relevant to explain the difference in APC-resistance between second and third generation of COCs. In general, direct comparisons of effects of different types of COCs on haemostatic variables are available for only a very few factors, which hampers the drawing of general conclusions with respect to haemostatic consequences.
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