Effect of testosterone on atherogenesis in cholesterol-fed rabbits with similar plasma cholesterol levels

The aim was to examine the effect of testosterone on atherogenesis in cholesterol-fed, castrated male rabbits not mediated via different plasma cholesterol levels. The rabbits in the testosterone group ( n = 19) and in the placebo group ( n = 17) were injected intramuscularly twice weekly for 17 weeks with 25 mg testosterone enantate and placebo, respectively, reaching plasma testosterone levels of 50–150 nmol/l in the testosterone group. No effect of testosterone on liver function or body weight was detected, but at week 15 mean blood pressure was 75 ± 2 mmHg (mean ± S.E.) in the testosterone group compared with 69 ± 2 mmHg in the placebo group ( P < 0.05). To reduce variation in plasma cholesterol between the two groups, the amount of cholesterol fed to each rabbit was adjusted on the basis of weekly determinations of plasma cholesterol; the mean plasma cholesterol levels during the 17 weeks were 20.9 ± 1.0 and 20.4 ± 0.9 mmol/l for the placebo and testosterone groups. In the intima-inner medias of the aortic arch, the thoracic and the abdominal aorta there were no consistent significant differences in aortic cholesterol content, expressed either as nmol/cm 2 or nmol/mg protein, between the two groups. However, the aortic cholesterol content tended to be lower in the testosterone group than in the placebo group. These findings suggest that in cholesterol-fed, castrated male rabbits, testosterone does not promote atherogenesis by an effect directly on the arterial wall.