Testosterone Supplementation in Healthy Men with Severe Short-Term Energy Deficit Prevents Increase in Circulating Ghrelin without Suppressing Appetite

Testosterone supplementation prevents an increase in circulating ghrelin but does not appear to affect appetite or energy intake in healthy men who are suffering from a severe, short-term energy deficit, according to a study recently published in the Journal of the Endocrine Society.

Researchers led by J. Philip Karl, PhD, RD, and Stefan M. Pasiakos, PhD, FACSM, both of the Military Nutrition Division at the U.S. Army Research Institute of Environmental Medicine in Natick, Mass., point out that severe energy deficits are common in military personnel during training, since these personnel are unable or unwilling to match such incredible energy expenditures. When this happens, they lose total body mass (TBM) and fat free mass, and their physical performance declines. The authors go on to write that substantial reductions in circulating testosterone likely contribute to these losses.

Energy deficits cause adaptive responses in order to stimulate the appetite and promote regaining TBM, and the authors note that ghrelin is thought to be an endocrine mediator of this response. Circulating ghrelin concentrations may also be regulated by testosterone, the authors write, since ghrelin is expressed in human testes, and testosterone supplementation suppresses circulating total ghrelin in pre-pubertal boys and weight-stable, non-obese, eugondal men. “This effect, if present in non-obese men during severe energy deficit, may have the unintended and undesirable consequence of blunting energy deficit-induced increases in ghrelin and, subsequently, appetite,” the authors write.

The researchers sought to explore the relationship among testosterone, ghrelin, appetite, TBM, and body composition during severe energy deficit and TBM recovery. Fifty healthy, physically active men with normal testosterone levels completed a randomized, double-blind trial that consisted of three phases. For Phase 1, the participants carried on their normal lives, but ate a TBM-maintaining diet for 14 days. Immediately following Phase 1, Phase 2 saw the participants admitted to an inpatient unit for 28 days, where they were assigned to two treatment groups – either receiving testosterone supplementation or placebo.

Phase 3 began on day 43 of the study, during which participants returned to their normal diet and exercise routines. The participants were followed for another 14 days, and if by day 56 they had regained ±2.5% of TBM, end-of-study measurements were initiated. If participants had not met that threshold, they were followed until they regained ±2.5% TBM or day 84, whichever came first.

The researchers found that the participants taking placebo saw their ghrelin concentrations increase during their energy deficit and returned to Phase 1 values by the end of the study. Those taking testosterone saw no changes in their ghrelin concentrations.

“Testosterone supplementation therefore appears unlikely to appreciably influence appetite or energy intake in non-obese young men, to include military personnel, during and following periods of unavoidable severe energy deficit,” the authors conclude. “However, observations strengthen evidence of testosterone-ghrelin interactions, and provide additional insight into endocrine factors potentially linking energy homeostasis and male reproductive function.”

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