Doses of hCG far lower than those used clinically increase IT-T concentrations in a dose-dependent manner in normal men with experimental gonadotropin deficiency. Assessment of IT-T provides a valuable tool to investigate the hormonal regulation of spermatogenesis in man.

Objective In men with prostate cancer, androgen deprivation reduces insulin sensitivity; however, the relative roles played by testosterone and estradiol are unknown. To investigate the respective effects of these hormones on insulin sensitivity in men, we employed a model of experimental hypogonadism with or without hormone replacement. Design Placebo-controlled, randomized trial. Participants 22 healthy male volunteers, 18–55 years old. Methods Following screening, subjects received the gonadotropin releasing hormone antagonist acyline plus one of the following for 28 days: Group 1, placebo transdermal gel and placebo pills; Group 2, transdermal testosterone gel 10g/day plus placebo pills; Group 3, transdermal testosterone gel 10 g/day plus the aromatase inhibitor anastrozole 1 mg/day to normalize testosterone while selectively reducing serum estradiol. Fasting insulin, glucose, adipokines and hormones were measured bi-weekly. Results With acyline administration, serum testosterone was reduced by >90% in all subjects in Group 1. In these men, mean fasting insulin concentrations were significantly increased compared with baseline (p=0.02) at 28 days, despite stable body weight and no changes in fasting glucose concentrations. Decreased insulin sensitivity also was apparent in the insulin sensitivity indices HOMA-IR (p=0.03) and QUICKI (p=0.04). In contrast, in Groups 2 and 3, testosterone concentrations remained in the physiologic range, despite significant reduction in mean estradiol in Group 3. In these groups, no significant changes in insulin sensitivity were observed. Conclusions Acute testosterone withdrawal reduces insulin sensitivity in men independent of changes in body weight, whereas estradiol withdrawal has no effect. Testosterone appears to maintain insulin sensitivity in normal men.

Sex steroids are essential for spermatogenesis; however, normal intratesticular concentrations of these hormones in man have not been extensively studied. To improve our understanding of intratesticular hormone concentrations, we performed bilateral testicular aspirations in a group of normal men, determined sex steroid concentrations within each testis, and compared these levels to serum hormone concentrations. Ten healthy human subjects aged 20-49 underwent bilateral testicular aspirations. Intratesticular hormone concentrations of testosterone, dihydrotestosterone (DHT), and estradiol were measured using liquid chromatography-tandem mass spectrometry. Intratesticular testosterone concentrations ranged from 119 to 1251 ng/mL, with a mean of 635 6 368 ng/mL. Intratesticular estradiol ranged from 0.41 to 3.9 ng/mL, with a mean of 2.4 6 1.3 ng/mL. Intratesticular DHT ranged from 1.1 to 7.9 ng/mL, with a mean of 3.5 6 3.2 ng/mL. Intratesticular testosterone and estradiol concentrations correlated highly with serum luteinizing hormone (LH; r 5 0.87 and r 5 0.70 respectively, P , .01). Intratesticular testosterone correlated highly with serum testosterone. Moreover, a significant correlation between the right and left testes was observed for testosterone (r 5 0.82, P 5 .003), but not for estradiol or DHT. Intratesticular hormone concentrations can be safely assessed by testicular aspiration. Intratesticular testosterone and estradiol correlate highly with serum LH concentrations, and variation in serum LH accounts for most of the variation in intratesticular testosterone among men. In addition, intratesticular testosterone is highly correlated between testes in a given individual. Direct measurement of intratesticular testosterone will improve our understanding of the relationship between intratesticular sex steroids and spermatogenesis, and may have implications for the development of male hormonal contraception.

Exogenous androgens can lower HDL-cholesterol (HDL-C) concentrations, yet men with low serum testosterone have elevated rates of cardiovascular disease (CVD). HDL function may better predict CVD risk than absolute HDL-C quantity. We evaluated the acute effects of medical castration in men on HDL-C, cholesterol efflux capacity and HDL protein composition. Twenty-one healthy men, ages 18–55, received the GnRH antagonist acyline and one of the following for 28 days: Group 1: placebo, Group 2: transdermal testosterone gel and placebo, Group 3: transdermal testosterone gel and an aromatase inhibitor. Sex steroids, fasting lipids, and cholesterol efflux to apoB-depleted serum were measured in all subjects. The HDL proteome was assessed in Group 1 subjects only. In Group 1, serum testosterone concentrations were reduced by >95%, and HDL-C and cholesterol efflux capacity increased (p=0.02 and p=0.04 vs. baseline, respectively). HDL-associated clusterin increased significantly with sex steroid withdrawal (p=0.007 vs. baseline). Testosterone withdrawal in young, healthy men increases HDL-C and cholesterol efflux capacity. Moreover, sex steroid deprivation changes HDL protein composition. Further investigation of the effects of sex steroids on HDL composition and function may help resolve the apparently conflicting data regarding testosterone, HDL-C, and CVD risk.