Low Serum Testosterone and Sex-Hormone-Binding-Globulin in Massively Obese Men

Abstract

Reproductive hormonal dynamics were assessed in 10 massively obese men, 200–380% of ideal body weight (percentage ideal body weight) and 11 similarly-aged controls who were 85–135% of ideal body weight. The mean serum testosterone of the obese group was significantly lower than normal (223.1 ± 26.9 (sem) ng/dl vs. 599.2 ± 58.1 ng/dl, P < 0.001). Despite their reduced serum testosterone levels, the obese subjects had normal secondary sexual characteristics except for slightly decreased facial hair and normal sized testes. The mean sex-hormone-binding-globulin level of the obese group was also lower than normal (0.247 ± 0.037 (sem) μg dihydrotestosterone bound/dl vs. 0.672 ±0.125 μg/dl, P < 0.01), while their mean per cent free testosterone, determined by equilibrium dialysis, was higher than normal (4.19 ± 0.29 (SEM) % vs. 2.04 ± 0.08%, P < 0.001). Though the mean free testosterone was not significantly different in the 2 groups (obese 9.5 ± 1.3 (SEM) ng/dl, normal 12.1 ± 1.1 ng/dl), within the obese group there were significant negative correlations between total serum testosterone and percentage ideal body weight (r = −0.85, P < 0.01), as well as between free testosterone and percentage ideal body weight (r = −0.70, P < 0.05). Two of the most obese subjects (wt > 220 kg) had free testosterone concentrations more than two standard deviations below the normal mean. Within the obese group, there was no significant correlation of sex-hormone-binding-globulin with total serum testosterone, free testosterone, or percentage ideal body weight. Baseline serum LH and FSH were normal in 9 obese subjects, including the 2 with low free testosterone, and elevated in one whose free testosterone was normal. The increases in serum LH after LHRH were not subnormal in the obese group, and the 2 subjects with low free testosterone did not have supranormal responses. Increases in serum LH and FSH after clomiphene were normal in the obese group. The serum testosterone of the obese group increased by a mean of 190% after clomiphene and by a further 120% (mean) after HCG, with all subjects attaining a serum testosterone over 600 ng/dl, thus indicating substantial testicular reserve. We conclude that, in massively obese men, 1) serum testosterone and sex-hormone-binding-globulin are low, 2) total serum testosterone and free testosterone correlate negatively with weight but do not correlate significantly with sex-hormone-binding-globulin, 3) responses to LHRH, HCG, and clomiphene indicate substantial reproductive hormonal axis reserve, and 4) a subpopulation (2/10) of the most massively obese subjects may have a defect in the hypothalamic-pituitary axis as suggested by its low free testosterone in the absence of elevated gonadotropins or hyper-response to LRH.