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

Abstract

Abstract The effects of castration alone, or followed by administration of 17β-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 17β-oestradiol (50 to 500 μg kg−1 day−1 i.p.), testosterone (500 μg 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 (17ṁ9 ± 0ṁ4 s) than in sham-operated rats (19sham-operatedl ± 0ṁ6 s). Warfarin, over the first 24 h of its administration, caused a significant (P < 0ṁ01) fall in PCA in each group of rats, the fall PCA in castrated rats pretreated with vehicle being significantly (P < 0ṁ05) less than that seen in the sham-operated rats. The fall was the same in castrated rats given vehicle or those given 17β-oestradiol. In contrast, warfarin caused a greater fall in PCA in the presence of testosterone than in the other groups of castrated rats.