Natural androgens inhibit male atherosclerosis - A study in castrated, cholesterol-fed rabbits

The effect of natural androgens on serum lipids and atherosclerosis is cont roversial. We therefore studied this important issue prospectively in an an imal model of atherosclerosis. Eighty male rabbits were randomized to bilat eral castration, and 20 animals were sham operated. The castrated rabbits w ere randomized to 500 mg oral dehydroepiandrosterone (DHEA) daily, 80 mg or al testosterone undecanoate (TU) daily, or 25-mg intramuscular injection of testosterone enanthate (TE) twice weekly, whereas the fourth castrated gro up (placebo) and the sham-operated rabbits did not receive any hormones. Al l animals were fed a cholesterol-rich diet during the 30-week treatment per iod. Average serum lipids and atherogenic lipoproteins were higher in the p lacebo group than in the other groups (ANOVA, P<0.0001). Aortic atheroscler osis, as evaluated by the cholesterol content (nmol/mg protein), was also h ighest in the placebo group (308+/-39) and lowest in the TE group (61+/-12) , but was intermediate in the DHEA(155+/-30), TU (191+/-43), and sham opera tion (162+/-29) groups (ANOVA, P<0.0001). ANCOVA indicated that the androge n effect on aortic atherosclerosis was only in part explained by the change s in lipoproteins. Aortic estrogen receptor contents were significantly low er in the androgen-treated groups than in the control groups, whereas there was no difference in aortic androgen receptor contents between groups. Nat ural androgens inhibit aortic atherosclerosis in castrated male rabbits onl y partly through a lipid-mediated effect.