Genomic effects of T are exerted via the AR. The length of the polymorphic CAG repeat sequence in the AR gene is inversely correlated with the transcriptional regulation of target genes by T. In 110 healthy men (20-50 yr), we investigated the interactions among this polymorphism, serum levels of sex hormones, cardiovascular risk factors, and flow-mediated and nitrate-induced vasodilatation of the brachial artery. The number of CAG repeat had no significant correlations with serum concentrations of total or free T. Stepwise multiple regression analysis revealed positive correlations of the number of CAG repeat with serum levels of high density lipoprotein cholesterol (partial r = 0.44; P < 0.001) and flow-mediated vasodilatation (partial r = 0.37; P < 0.001). The association of CAG repeat with high density lipoprotein (HDL) cholesterol was independent of body fat content and serum levels of free T, which both had significant negative correlations with HDL cholesterol. The association of CAG repeat with flow-mediated vasodilatation was independent of cigarette smoking and serum levels of free T and low density lipoprotein cholesterol, which also were correlated with flow-mediated vasodilatation. We conclude that a low number of CAG repeat in the AR gene implies a greater chance for low levels of HDL cholesterol and reduced endothelial response to ischemia, which are both important risk factors for coronary heart disease.

A high number of CAG repeats within the androgen receptor gene attenuates testosterone effects on bone density and bone metabolism. This seems to be associated with accelerated age-dependent bone loss.

Interindividual differences in gonadotropin suppression achieved by short-and long-acting intramuscular testosterone (T) preparations were studied to detect factors hindering complete suppression of gonadotropins as the prerequisites for effective male contraception. Forty healthy men received a single injection of T propionate; 4 weeks later they received 2 injections of 1000 mg of T undecanoate (TU) given 6 weeks apart. Following TU, declines of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were consistent in 17.5% and almost absent in 25% of men.Men showing the most rapid and consistent declines in LH and FSH levels received a slightly higher dose per body weight of TU (13.1 6 0.6 vs 11.3 6 0.6 mg/kg; P 5 NS) and reached higher maximal concentrations of total T (40 6 4.8 vs 18.4 6 2.4 nmol/L; P , .001) and free T as well as estradiol. Men with high fat mass (mean 6 SEM, 10.3 6 1.5 vs 23.2 6 6.4 kg) had a delayed increase in T levels and an impaired relative decline in LH (12 6 2% vs 53 6 10%) and FSH (17 6 6%. vs 70 6 25%) levels within the first 2 weeks after the first TU injection. We conclude that overweight reduces the chance of rapid and profound gonadotropin suppression during treatment with TU. Body weight needs to be considered to avoid failure of hormonal male contraception.