Atherosclerosis in apolipoprotein E-deficient mice is decreased by the suppression of endogenous sex hormones

To elucidate the influence of gonadotropins, endogenous sex hormones and testosterone on atherosclerosis, 4-week-old male and female apoE-deficient mice received either 100 mug subcutaneous injections of the gonadotropin-releasing hormone (GnRH) antagonist Cetrorelix every 48 hours or a subcutaneous implantation of a permeable silastic tube with 35 mg of testosterone. Control mice received either subcutaneous injections of saline, a silastic implant with saline, or no treatment. The animals were sacrificed after eight weeks of treatment; blood was obtained by cardiac puncture and the aorta was taken out and prepared. The suppression of testosterone led to an increase in atherosclerosis in both the sinus aortae and the ascending aorta despite increases of cholesterol in male and decreases of HDL cholesterol in female mice. Treatment with testosterone led to small but significant increases of cholesterol levels and atherosclerotic lesions in male mice. Female mice showed no change in lipids and fewer atherosclerotic lesions. In conclusion, the suppression of gonadotropins appears to have a moderate anti-atherogenic effect. The effect of testosterone appears to be either neutral or opposed by gonadotropins.