Acute effects of testosterone on whole body protein metabolism in hypogonadal and eugonadal conditions: a randomized, placebo-controlled, crossover study.

Chronic testosterone (T) substitution and short-term T administration positively affect protein metabolism, however, data on acute effects in humans are sparse. This study aimed to investigate T's acute effects on whole body protein metabolism in hypogonadal and eugonadal conditions. We designed a randomized, double-blind, placebo-controlled, crossover study, including 12 healthy young males. Whole body protein metabolism was evaluated during 1 ) eugonadism, and after medically induced hypogonadism, with application of a gel on each trial day containing either 2 ) placebo, 3 ) T 50 mg, or 4 ) T 150 mg; under basal (5-h basal period) and insulin-stimulated conditions (3-h clamp). The main outcome measure was a change in net protein balance. The net protein loss was 62% larger in the placebo-treated hypogonadal state compared with the eugonadal state during the basal period (-5.5 ± 3.5 µmol/kg/h vs. -3.4 ± 1.2 µmol/kg/h, P = 0.038), but not during the clamp ( P = 0.06). Also, hypogonadism resulted in a 25% increase in whole body urea flux ( P = 0.006). However, T did not result in any significant changes in protein breakdown, synthesis, or net balance during either the basal period or clamp (all P > 0.05). Protein breakdown was reduced during clamp compared with the basal period regardless of gonadal status or T exposure (all P ≤ 0.001). In conclusion, the application of transdermal T did not counteract the negative effects of hypogonadism with no effects on protein metabolism within 5 h of administration. Insulin (during clamp) mitigated the effects of hypogonadism. This study is the first to investigate acute protein metabolic effects of T in hypogonadal men. NEW & NOTEWORTHY In a model of medically induced hypogonadism in male volunteers, we found increased whole body urea flux and net protein loss as an expected consequence of hypogonadism. Our study demonstrates the novel finding that the application of transdermal testosterone had no acute effects on whole body protein metabolism under eugonadal conditions, nor could it mitigate the hypogonadism-induced changes in protein metabolism. In contrast, insulin (during clamp) mitigated the effects of hypogonadism on protein metabolism.