Effect of dienogest on bleeding time, coagulation, fibrinolysis, and platelet aggregation in female rats.

We investigated the effect of dienogest on bleeding time, coagulation, fibrinolysis, and platelet aggregation in female rats compared with that of medroxyprogesterone acetate (MPA) and danazol, in order to elucidate the reason for relatively high incidence of bleeding in dienogest-treated patients with endometriosis. Dienogest caused no change in the bleeding time at a single dose of 100 mg/kg or at a repeated dose of 10 mg/kg per day for 2 weeks. The drug increased the fibrinogen level, coagulation factor II and V activities, and antithrombin III activity, but had no effect on fibrinolysis or on platelet aggregation at repeated doses of 1 and 10 mg/kg per day for 4 weeks. MPA significantly shortened the bleeding time at the same doses as dienogest. MPA increased the fibrinogen level and plasminogen activity, potentiated the platelet aggregation, and increased the platelet cholesterol-to-phospholipid ratio at a repeated dose of 10 mg/kg per day for 4 weeks. Danazol significantly shortened the bleeding time like MPA. Danazol increased the fibrinogen level, coagulation factor II, V, VII, VIII, IX, X, XI, and XII activities, and antithrombin III activity, but had no influence on the platelet aggregation at repeated doses of 10 and 100 mg/kg per day for 4 weeks. In comparison with MPA and danazol, dienogest may induce a relatively high incidence of bleeding in patients with endometriosis partially because of its minimal effect on hemostasis.