Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a cross-over study

Combined oral contraceptives (OC) are known to increase the risk of venous thromboembolism. The aim of this randomized, cycle-controlled, cross-over s tudy in 28 healthy volunteers was to assess potential differences between t he effects of an OC containing 150 mu g levonorgestrel (as representative o f the so-called second generation OC) and an OC containing 150 mu g desoges trel las representative of the third generation OC) in combination with 30 mu g ethinylestradiol on several coagulation factors and markers of thrombi n formation. All participants used each QC for two cycles, and were switche d to the other OC after a washout period of two menstrual cycles. The plasm a concentrations of factors II, VII, X, and fibrinogen significantly increa sed during use of both the levonorgestrel- and desogestrel-containing OC's. The plasma concentrations of factor VIII increased, and of factor V decrea sed, changes which only reached statistical significance during the use of the desogestrel-containing OC. During exposure to the desogestrel-containin g OC, as compared with the levonorgestrel-containing OC, both factor VII an d factor II showed a greater increase (FVII: 32% and 12% respectively; p <0 .0001; F11: 16% and 12% respectively; p = 0.048, whereas factor V showed a greater decrease (-11% and -3% respectively: p = 0.010). Only one of the ma rkers for ongoing coagulation (prothrombin fragment 1+2) showed a significa nt increase during OC use. whereas concentrations of thrombin-antithrombin complexes and soluble fibrin remained unchanged. For these markers, then wa s no difference between the tested OC's. We conclude that then are differen ces between the effects of levonorgestrel and desogestrel-containing OC's o n some coagulation factors. Whether these changes provide a biological expl anation for the reported differences in venous thromboembolic risk is as ye t unclear. The real challenge now becomes to define a pattern of changes in the various systems which, if affected simultaneously, may tip the hemosta tic balance towards a prethrombotic state and may lead to overt clinical ve nous thromboembolism.