OC 62.5 - Effect of estetrol and drospirenone combination on blood coagulation and fibrinolysis in Japanese patients with endometriosis

Background: Combined oral contraceptives (COCs) are prescribed for women with endometriosis. Ethinylestradiol (EE) is a widely used estrogen, combining with a progestin; however, a safety concern is the increased risk of venous thromboembolism (VTE). Estetrol (E4) is a native and selective estrogen produced in the fetal liver, and E4/drospirenone (DRSP) was found to have little effects on sex hormone-binding globulin (SHBG) and liver proteins regulating blood coagulation and fibrinolysis under the estrogen-control.

Aims: This study investigated the effects of E4/DRSP on coagulation and fibrinolysis in patients with endometriosis.

Methods: This is a 12-week, multicenter, randomized, open-label, active-controlled, parallel-group study. Eligible subjects were randomly allocated to either E4 15 mg/DRSP 3 mg or EE 20 µg/DRSP 3 mg group. Both combinations were administered once a day for 12 weeks with cyclic, 24-day active followed by 4-day hormone-free and flexible extended regimens, respectively. Point estimates and two-sided 95% confidence intervals were inferred for relative change from baseline in coagulation and fibrinolysis markers. The study was approved by the institutional review boards and written informed consent was obtained from all participants.

Results: The effects on coagulation and fibrinolysis were fewer in the E4/DRSP group than in the EE/DRSP group. Anticoagulant proteins, protein S and tissue factor pathway inhibitor were reduced following EE/DRSP, thereby activated protein C sensitivity ratio (ETP-based) was significantly increased by approximately 4-fold compared to E4/DRSP. Eventually, fibrinolysis was triggered to compensate for the disturbed coagulation and D-dimer levels which were increased in the EE/DRSP group but less in the E4/DRSP group (Figure)

Conclusion(s): VTE is a safety concern in COC users and aging is a risk factor. This study demonstrated that the effect of E4/DRSP on coagulation and fibrinolysis was fewer than that of EE/DRSP in subjects with endometriosis, a disease in women of advanced and reproductive age.