title: Gender differences in response to chronic treatment with 17β-oestradiol and 17β-aminoestrogen pentolame on hemostasis in rats.
abstract: OBJECTIVE
  This work evaluated chronic treatment with 17β-oestradiol (E2) 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.
  
  
  METHODS
  Rats (n=12-18) were treated every third day during three months with E2 (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 E2 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 E2 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). E2 and AEP decreased FIB in M and Ovx animals. Decreases in FIB by E2 were more pronounced in male (15-18% P<0.05) than in ovariectomized rats (10-14% P<0.05). E2 showed more potency than AEP, lowering FIB at 1 and 10 μg/kg doses. Both estrogens decreased FIB in ovariectomized animals (E2, 10-14%, P<0.05; AEP, 9% P<0.05) and were reverted by increasing dosage.
  
  
  CONCLUSIONS
  Gender influenced response to chronic treatment with E2 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.
authors.affiliation: Departament of Pharmacology, National Autonomous University of Mexico. Av. Universidad No. 3000, Ciudad Universitaria, Colonia Copilco Universidad, Delegación Coyoacán, Mexico City, Mexico.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemini
authors.forename: Ruth
authors.initials: R
authors.lastname: Jaimez
authors.forename: Martha
authors.initials: M
authors.lastname: Medina-Jiménez
authors.forename: María Estela
authors.initials: ME
authors.lastname: Ávila
mesh_terms: D000605:Amino Alcohols / Q000494:pharmacology*; D000818:Animals; D001780:Blood Coagulation Tests; D004958:Estradiol / Q000494:pharmacology*; D045166:Estradiol Congeners / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D008297:Male; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
chemical_list: D000605:Amino Alcohols; D045166:Estradiol Congeners; D004963:Estrenes; D004967:Estrogens; C083220:pentolame; D004958:Estradiol