SEX-DIFFERENCES IN THE ANTICOAGULANT EFFECTS OF WARFARIN

Sex differences in the anticoagulant effects of warfarin were studied in rats. Warfarin was administered to rats from 7 days of gestation until 14 weeks of age. In male rats, the normal prothrombin level in the plasma was reduced, and the blood coagulation time was prolonged by treatment with warfarin at 4, 9 and 14 weeks of age. However, in female rats, the effects of warfarin on the prothrombin level and blood coagulation time were observed at 4 weeks to the same degree as in male rats, but these effects were reduced with aging, and at 14 weeks, no effect of warfarin was observed. Rats ovariectomized at 12 weeks of age and subsequently treated with warfarin for 2 weeks showed prolongation of blood coagulation time to the same level as in warfarin-treated male rats, which was inhibited by administration of 17 beta-estradiol (100 mu g/kg /day for 4 days, i.m.). In male rats, treatment with 17 beta-estradiol also inhibited the anticoagulant effects of warfarin without changing the warfarin level in plasma. These results suggest that there is a sex difference in the anticoagulant effects of warfarin, and that this difference may be related to the estradiol level in plasma.