Gonadal hormones and pathogenesis of occlusive arterial thrombosis

Arterial thrombus formation was induced in male and female Wistar rats (3 mo) by inserting a loop-shaped polyethylene cannula into the abdominal aorta. Thrombogenesis was also induced in mature male and female New Zealand rabbits by constriction of the femoral artery and injection of ellagic acid. The criteria for thrombus development in the cannulated rats were: incidence of thrombosis (IT), obstruction time (OT), and thrombus weight (TW). We observed a significant sex difference in all these criteria of thrombogenesis in both rats and rabbits. Pretreatment of either sex with Depo-testosterone shortened OT, increased TW about fivefold in males and threefold in females, and increased mortality rate (MR) more than fourfold in both sexes. Prolonged pretreatment with Depo-testosterone increased in all aspects of thrombogenesis. Depo-estradiol had marginal ameliorating effects in male rats only. Both the antiandrogen Flutamide, and aspirin, significantly decreased the thrombogenic effects of testosterone. Thus, testosterone may be a significant risk factor in experimentally induced thrombogenesis in rats and rabbits.