Graded Testosterone Infusions Distinguish Gonadotropin Negative-Feedback Responsiveness in Asian and White Men—A Clinical Research Center Study1

Abstract

Recently, multicenter clinical trials to determine male contraceptive efficacy disclosed that testosterone-induced suppression of spermatogenesis to azoospermia occurred in about 90% of Asian but only 60-70% of white men. To test whether there are ethnic differences in the sensitivity of gonadotropin secretion to suppression by testosterone, we administered constant infusions of testosterone at 0, 7, 14, and 28 mg/1.7 m2 x 24 h i.v. for 48 h to 9 Asian and 8 white normal male volunteers (22-42 yr old). During the last 8 h of each infusion dose, 10-min frequent blood sampling was carried out for later LH and FSH measurements by sensitive fluoroimmunoassays. Analyses of LH secretory pulses showed that LH pulse width, height, area, and total area under the curve (LH concentration vs. time) were significantly more suppressed in Asians than in whites during the lowest infusion dose of testosterone. With increasing testosterone dose, the suppression of pulsatile LH secretion was not different in the two ethnic groups. In contrast to pulsatile LH secretion, the responsiveness of pulsatile FSH secretion to exogenous testosterone infusion was not different between the two ethnic groups. At baseline, Asian men had a significantly higher mean number of FSH pulses and mean incremental pulse heights than did white men. Serum inhibin B levels were not distinguishable in the two ethnic groups, but the FSH profiles were quantifiably more irregular (higher approximate entropy) in the Asian volunteers. Our data suggest that, compared with white men, Asian men respond earlier and with more marked suppression of pulsatile LH secretion to ramped testosterone infusions. The elevated basal serum FSH concentrations (and more irregular FSH release pattern) observed in Asian men may suggest a small relative decrease in spermatogenic reserve and/or gonadal negative feedback. Whether these differences contribute to the observed differences in suppression of spermatogenesis in Asians vs. non-Asians in male contraceptive studies is not yet known.