DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY ON THE EFFECTS OF THE MONOPHASIC ORAL-CONTRACEPTIVE CONTAINING 30 MU-G ETHINYL ESTRADIOLAND 2.00 MG DIENOGEST ON THE HEMOSTATIC SYSTEM

Forty healthy female volunteers aged between 19 and 35 years (27.3 +/- 4.1 years) with normal menstrual cycles were included in a double-bli nd, randomized, placebo-controlled study to investigate the influence on the hemostatic system of an oral contraceptive containing 30 mu g e thinyl estradiol in combination with 2.00 mg dienogest, which is a 19- norprogestin without a 17 alpha-ethinyl group. At baseline and during one treatment cycle, 12 hemostatic parameters were measured on cycle d ays 7, 14, and 21. The hemostatic parameters were categorized as eithe r procoagulatory, anticoagulatory and profibrinolytic, or antifibrinol ytic and indicative of fibrin turnover. Differences between placebo an d 30 mu g ethinyl estradiol and 2.00 mg dienogest of plasma levels of hemostatic parameters on cycle days 21 of the precycle and treatment c ycle were chosen as target variables. Prothrombin fragment 1 + 2 (F 1 + 2) was chosen as the main target variable. Equivalence of F 1 + 2 be tween placebo and active treatment was noted. Among the procoagulatory factors, only factor VII activity was found to be increased over plac ebo in the active treatment group, but decreased in the placebo group. Protein C activity increased during the treatment with 30 mu g ethiny l estradiol and 2.00 mg dienogest, and was higher than that of the pla cebo group in which this parameter decreased during the treatment cycl e. There was a corresponding increase in fibrinolytic activity being r eflected by higher plasminogen levels in the active treatment group in comparison with placebo. An increase was noted for the fibrinolytic p arameter D-dimer. Apart from isolated measurements, the parameters rem ained in their respective normal ranges. The data combine to suggest t hat 30 mu g ethinyl estradiol and 2.00 mg dienogest has a balanced eff ect on the hemostatic system stimulating both procoagulatory and fibri nolytic activity. (C) 1997 Elsevier Science Inc. All rights reserved.