title: Changes on hemostatic parameters induced by 17beta-estradiol, ethinylestradiol, and the 17beta-aminoestrogen pentolame in the male Wistar rat.
abstract: Oral contraceptives containing estrogens increases the incidence of thromboembolic events. In contrast, administration of 17beta-aminoestrogens prolonged blood clotting time (BCT) in rodents. We studied the effect of estradiol (E(2)), ethinylestradiol (EE) and pentolame on some screening hemostatic tests. BCT was evaluated 24, 48, 72 and 96 h post-treatment. Rats received subcutaneously (s.c.) for five consecutive days E(2) (0.1-1000 microg), EE (1-1000 microg), pentolame (0.1-1000 microg), or vehicle (propyleneglycol 0.3 ml). At 48 h post-treatment E(2) (1000 microg) diminished BCT (32%, P<0.01), in contrast pentolame (1000 microg) augmented BCT by 41% (P<0.01). After 72 h, E(2) showed procoagulant effects with 10, 100 and 1000 microg doses (-45, -30, and -21%, respectively). Significant effects on BCT of EE were observed 72 h after with 1000 microg (-12%, P<0.05). Animals were treated s.c. for two consecutive days with E(2) (3mg/100g), pentolame (4 mg), or vehicle (0.1 ml). BCT, bleeding time (BT), platelet aggregation (PA), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen concentration were determined. E(2) produced a significant diminution on BCT (-20%) after 72 h whereas pentolame increased BCT from 24 to 96 h (62%, maximal response at 48 h). APTT and PT coagulation times of the groups treated with E(2) and pentolame were lengthened (33 and 29%; 16 and 24%, respectively; P<0.05). Fibrinogen concentration increased (115%, P<0.01) only in the pentolame-treated group. Pentolame and E(2) produced any effects on BT and PA compared with control groups, indicating that platelet function was not modified. Our results indicate that E(2), EE and pentolame affects the plasmatic phase of the hemostatic mechanism.
authors.affiliation: Departamento de Hematología CMN, La Raza IMSS, Mexico DF, Mexico.
authors.forename: Aurora
authors.initials: A
authors.lastname: García-Manzano
authors.forename: José
authors.initials: J
authors.lastname: González-Llaven
authors.forename: Ruth
authors.initials: R
authors.lastname: Jaimez
authors.forename: Yanira
authors.initials: Y
authors.lastname: Franco
authors.forename: Ma
authors.initials: M
authors.lastname: Estela Avila
authors.forename: Consuelo
authors.initials: C
authors.lastname: Rubio-Póo
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemini
mesh_terms: D000605:Amino Alcohols / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001780:Blood Coagulation Tests; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology*; D004963:Estrenes / Q000737:chemistry / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000737:chemistry / Q000494:pharmacology*; D006490:Hemostatics / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000605:Amino Alcohols; D004963:Estrenes; D006490:Hemostatics; C083220:pentolame; D004997:Ethinyl Estradiol; D004958:Estradiol