The effects of 17 beta-oestradiol or testosterone on the response to S-warfarin in castrated male rats.

Abstract

The effects of castration alone, or followed by administration of 17 beta-oestradiol or testosterone, on the action of S-warfarin have been investigated in male Wistar rats castrated at 4 weeks of age. Six to 10 weeks later, blood samples were taken before, and at 24 h and 7 days after onset of administration of either 17 beta-oestradiol (50 to 500 micrograms kg-1 day-1 i.p.), testosterone (500 micrograms kg-1 day-1 i.p.), or vehicle (polyethylene glycol 200 i.p.). On the seventh day of these interventions, S-warfarin (6.3 mg kg-1 i.p.) was given; prothrombin complex activity (PCA) was then measured over the next 72 h. In addition, a group of sham-operated rats were given S-warfarin, alone. The control prothrombin times were lower in castrated rats (17.9 +/- 0.4 s) than in sham-operated rats (19.1 +/- 0.6 s). Warfarin, over the first 24 h of its administration, caused a significant (P less than or equal to 0.01) fall in PCA in each group of rats, the fall in PCA in castrated rats pretreated with vehicle being significantly (P less than or equal to 0.05) less than that seen in the sham-operated rats. The fall was the same in castrated rats given vehicle or those given 17 beta-oestradiol. In contrast, warfarin caused a greater fall in PCA in the presence of testosterone than in the other groups of castrated rats.