Effects of Testosterone Supplementation on Ghrelin and Appetite During and After Severe Energy Deficit in Healthy Men

Abstract

Background: Severe energy deficits cause interrelated reductions in testosterone and fat free mass. Testosterone supplementation may mitigate those decrements, but could also reduce circulating concentrations of the orexigenic hormone ghrelin, thereby exacerbating energy deficit by suppressing appetite.

Objective: To determine whether testosterone supplementation during severe energy deficit influences fasting and postprandial ghrelin concentrations and appetite.

Design and methods: Secondary analysis of a randomized, double-blind trial that determined the effects of testosterone supplementation on body composition changes during and following severe energy deficit in nonobese, eugonadal men. Phase 1 (PRE-ED): 14-day run-in; phase 2: 28 days, 55% energy deficit with 200 mg testosterone enanthate weekly (TEST; n = 24) or placebo (PLA; n = 26); phase 3: free-living until body mass recovered (end-of-study; EOS). Fasting and postprandial acyl ghrelin and des-acyl ghrelin concentrations and appetite were secondary outcomes measured during the final week of each phase.

Results: Fasting acyl ghrelin concentrations, and postprandial acyl and des-acyl ghrelin concentrations increased in PLA during energy deficit then returned to PRE-ED values by EOS, but did not change in TEST (phase-by-group, P < 0.05). Correlations between changes in free testosterone and changes in fasting acyl ghrelin concentrations during energy deficit (ρ = -0.42, P = 0.003) and body mass recovery (ρ = -0.38; P = 0.01) were not mediated by changes in body mass or body composition. Transient increases in appetite during energy deficit were not affected by testosterone treatment.

Conclusions: Testosterone supplementation during short-term, severe energy deficit in healthy men prevents deficit-induced increases in circulating ghrelin without blunting concomitant increases in appetite.

Clinical trials registration: www.clinicaltrials.gov NCT02734238 (registered 12 April 2016).

Keywords: androgen; hypogonadism; hypothalamic-pituitary-gonadal axis; military; weight cycling.

Published by Oxford University Press on behalf of the Endocrine Society 2020.

Figures

Figure 1.

Study design. Appetite and ghrelin measurements were included as secondary outcomes in the Optimizing Performance for Soldiers study [43, 44]. On study days 7, 43, and EOS + 1, appetite ratings and fasted blood samples were collected 15 minutes before a standardized breakfast, and every 30–60 minutes after starting breakfast for 180 minutes. Appetite was also measured by energy intake during a lunch meal consumed ad libitum (185 minutes). Blood samples were collected to measure fasting insulin, fasting leptin, and fasting and postprandial glucose, acyl ghrelin, and des-acyl ghrelin. EOS, end of study.

Figure 2.

Testosterone supplementation alters postprandial ghrelin responses during energy deficit. Fasting and postprandial acyl ghrelin (A-C), des-acyl ghrelin (D-F), total ghrelin (G-I), and the acyl ghrelin/des-acyl ghrelin ratio (J-L) measured during a standardized meal challenge (0–180 minutes) administered before (PRE; study day 7) and after (POST; study day 43) severe energy deficit (ED), and 1 day after body mass recovery (EOS). (A-B, D-E, G-H, J-K) Individual data points are mean ± SEM. (C, F, I, L) Boxes span 25th to 75th percentile with the median value represented by a solid line inside the box. Whiskers extend to minimum and maximum values or to 1.5 times the interquartile range if any values outside that range (represented by circles). Main effects of group, study phase, and their interaction on area under the postprandial response curve (AUC) analyzed by linear mixed models with Bonferroni corrections. (C, F, I) Group-by-phase interaction, P < 0.05. (L) Main effect of group, P = 0.05. (C, F, I, L) * P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001. PLA, placebo treatment group; TEST, testosterone treatment group.

Figure 3.

Testosterone supplementation does not affect appetite during energy deficit. Fasting and postprandial fullness (A-C), hunger (D-F), prospective consumption (Pro. Consumption, G-I), and desire to eat (J-L) measured during a standardized breakfast (0–180 minutes) followed by an ad libitum lunch meal (served at 185 minutes) administered before (PRE; study day 7) and after (POST; study day 43) severe energy deficit (ED), and one day after body mass recovery (EOS). (A-B, D-E, G-H, J-K) Individual data points are mean ± SEM. (C, F, I, L) Boxes span 25th to 75th percentile with the median value represented by a solid line inside the box. Whiskers extend to minimum and maximum values or to 1.5 times the interquartile range if any values outside that range (represented by circles). Main effects of group, study phase, and their interaction on area under the postprandial response curve (AUC) analyzed by linear mixed models with Bonferroni corrections. (C, F, I, L) Main effect of phase, P < 0.05. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001. PLA, placebo treatment group; TEST, testosterone treatment group.