Effects on haemostasis variables by second and third generation combined oral contraceptives: A review of directly comparative studies

Previous reports and reviews indicate differences in effects of second and third generation combined oral contraceptives (COCs) on haemostasis variabl es. This review analyses directly comparative studies on such effects. From the literature, 17 longitudinal comparative studies with parallel grou ps were retrieved, containing data on comparisons between COCs containing l evonorgestrel (second generation COCs) and COCs containing desogestrel, ges todene or norgestimate (third generation COCs) with 30-35 mu g ethinylestra diol. Six or more comparisons were available only for fibrinogen, platelet count, antithrombin ill, factor VII, factor VIII and factor X. The comparisons reveal a consistently larger increase in factor VII with th e 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, sug gesting a progestogen-specific dependence. Trends in antithrombin III are t owards more reduction for the third generation COCs, but the effects are ve ry minor. The effects on factor V suggest a possible progestogen specificit y, which may be relevant to explain the difference in APC-resistance betwee n second and third generation of COCs. In general, direct comparisons of ef fects 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.