Gender differences in response to chronic treatment with 17β-oestradiol and 17β-aminoestrogen pentolame on hemostasis in rats

OBJECTIVES: This work evaluated chronic treatment with 17β-oestradiol (E(2)) and 17β-aminoestrogen pentolame (AEP) on prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration (FIB). Male (M) and ovariectomized (Ovx) Wistar rats were used to explore gender differences in the pharmacological response. MATERIALS AND METHODS: Rats (n = 12-18) were treated every third day during three months with E(2) (1, 10, 100 μg/kg), AEP (1, 10, 100, 500 μg/kg) or vehicle (propylenglycol 1 ml/ kg). PT, aPTT, TT, and FIB were measured using standardized techniques. RESULTS: Chronic treatment with E(2) in male rats increased PT (4-7%; P < 0.05), decreased aPTT (9%; 100 μg/kg; P < 0.05) and decreased TT (5% at 100 μg/Kg; P < 0.05). Chronic treatment with E(2) in ovariectomized female rats decreased PT (3-4%; P < 0.05), did not induce significant changes on aPTT and decreased TT in a dose dependent manner (12-27%; P < 0.05). Chronic treatment with AEP in male rats did not alter PT, increased aPTT in a dose dependent manner (5-16%; P < 0.05), and decreased TT (5%; 500 μg/Kg; P < 0.05) while in female ovariectomized rats it decreased PT (5-9%; P < 0.05), increased aPTT (8-13%; P < 0.05) and decreased TT (6-13%; P < 0.05). E(2) and AEP decreased FIB in M and Ovx animals. Decreases in FIB by E(2) were more pronounced in male (15-18% P < 0.05) than in ovariectomized rats (10-14% P < 0.05). E(2) showed more potency than AEP, lowering FIB at 1 and 10 μg/kg doses. Both estrogens decreased FIB in ovariectomized animals (E(2), 10-14%, P < 0.05; AEP, 9% P < 0.05) and were reverted by increasing dosage. CONCLUSIONS: Gender influenced response to chronic treatment with E(2) and AEP on hemostatic parameters. PT and aPTT were the most affected parameters, demonstrating non-equivalence in the pharmacological response of M and Ovx rats.