Inhibitory effect of ethinylestradiol on coagulation factors in rats

Epidemiological and experimental data have indicated the beneficial and adverse effects of estrogenic replacement therapy. In the present study, we explored the effect of ethinylestradiol (EE) and 17β-estradiol (E₂) on screening tests, prothrombin time (PT) and activated partial thromboplastin time (APTT), as well as the activity of coagulation factors (FVII, FX, FXI, and FXII) in male Wistar rats. Animals were injected subcutaneously during three consecutive days with EE or E₂ (1, 3, 10, and 30 mg/kg) and propylene glycol (0.3 ml; vehicle, V). EE produced significant increments (P<0.05) on PT (8, 13, 15, and 10%) and APTT (32, 35, and 28%), whereas E₂ did not show any effect. EE diminished the activity of factors VII (-10, -13, and -10%) and X (-10, -9, -15, and -14%; P<0.05), and E₂ (1 mg/kg) produced a modest increment (8%; P<0.05) on FX only. E₂ (10 mg/kg) showed a diminution of 9% (P<0.05), while EE did not produce any response on factor XII. EE diminished (-15, -14, -19, and -17%) but E₂ augmented (10, 14, 24, and 24%) factor XI activity (P<0.05). Our findings suggest that EE and E₂ produce different effects on coagulation and that EE seems to act across an inhibitory mechanism of coagulation factor activity in the present experimental model.