Effects of Second and Third Generation Oral Contraceptives and their Respective Progestagens on the Coagulation System in the Absence or Presence of the Factor V Leiden Mutation

Abstract

SummaryCompared to second generation, the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis especially in women with the factor V Leiden mutation. To find an explanation for these risk differences we investigated the effects of desogestrel- and levonorgestrel-containing oral contraceptives as well as their progestagens separately on the coagulation system in the absence or presence of the factor V Leiden mutation.In a single center, double blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second generation (30 µg ethinylestradiol/150 µg levonorgestrel) or a third generation (30 µg ethinylestradiol/150 µg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of 2 menstrual cycles, the participants received the corresponding progestagen-only preparation containing 150 µg levonorgestrel or 150 µg desogestrel. In plasmas of the participating women fragment 1+2, factor V, VII, VIII, IX, X and XI were determined.Both combined oral contraceptives induced a decrease in factor V, whereas the levels of all other coagulant parameters increased. However, in women without the factor V Leiden mutation the effects of desogestrel-containing preparations were significantly different compared to levonorgestrel-containing oral contraceptives for factor V (−8.0; 95% Cl −13.4 to −2.6), factor VIl (26.8; 95% Cl 15.5 to 38.0) and factor IX (−9.6; 95% Cl −16.2 to −3.2). When these women used progestagen-only pills, a differential effect between desogestrel and levonorgestrel was only found for factor IX (−6.5; 95% CI –11.4 to –1.5).In carriers of the factor V Leiden mutation desogestrel-containing oral contraceptives induced more pronounced changes in factor V (−14.2; 95% CI −22.4 to −6.0) and factor VII (36.1; 95% CI 19.7 to 52.6) compared to levonorgestrel-containing oral contraceptives. Comparing desogestrel- and levonorgestrel-only, only for factor V a differential effect was found in these women (−9.5;95% CI –18.3 to –0.6).It appears that desogestrel-containing oral contraceptives have a more pronounced effect on the coagulation system than levonorgestrelcontaining oral contraceptives which may be explained by a less effective compensation of the thrombotic effect of ethinylestradiol by desogestrel.