Effects of testosterone supplementation on body composition and lower-body muscle function during severe exercise- and diet-induced energy deficit: A proof-of-concept, single centre, randomised, double-blind, controlled trial

Abstract

Background: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone.

Methods: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers.

Findings: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (-0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers.

Interpretation: Findings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline.

Funding: Collaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence.

Keywords: Anabolism; Hypogonadism; Hypothalamic-pituitary-gonadal axis; Lower-body muscle function; Military operational stress; Muscle mass; Semi-starvation.

Fig. 1

Participant flow chart. 553 individuals were assessed for eligibility, 279 were excluded, 274 were found eligible for screening, 221 were excluded following screening, 53 were enrolled, 3 discontinued participation prior to phase 2 (i.e., were not randomised), 50 were randomised and completed the intervention (24 into Testosterone and 26 into Placebo). ¹Taking medications or supplements (n = 11), irremovable metal (n = 16), allergies or food intolerance (n = 5), not physically active (n = 2), age (n = 5), body mass index (n = 9), did not meet >1 inclusion/exclusion criteria (n = 14); ²Recruitment complete/full (n = 28), could not contact (n = 17), not a citizen (n = 5), unknown (n = 1); ³Medical history or lab results (n = 18), smoking/drug use (n = 12), body mass index (n = 20), dietary limitations (n = 3), non-compliant with screening procedures (n = 9), not willing to receive testosterone injections (n = 1), head circumference too large for MRI machine (n = 1); ⁴Recruitment complete/full (n = 4), schedule conflict (n = 8).

Fig. 2

Experimental design. Adapted from Pasiakos et al. [14].

Fig. 3

Change in body weight and composition during energy deficit and recovery. Least squares mean ± standard error change in body weight (A) and composition (B) during Phase 2 (55% energy deficit) and Phase 3 (recovery/weight regain) relative to the final body weight and composition measured during Phase 1 (eucaloric diet) for Testosterone (n = 24), 55% energy deficit + 200 mg testosterone enanthate per week during Phase 2 (n = 24) and Placebo, 55% energy deficit + 1 mL sesame seed oil placebo per week during Phase 2 (n = 26). Data were analysed using linear mixed models, adjusting for age and pre-study value. Bonferroni corrections were used for post hoc comparisons. Data not sharing the same letter superscript within a treatment are different; and *indicates a between group difference (phase-by-treatment interaction).

Fig. 4

Muscle fibre type and percent distribution during energy balance and energy deficit. Representative images of serial cross-sections from vastus lateralis samples collected at rest, under fasted conditions during phase 1 (eucaloric phase, day 14) and phase 2 (55% energy deficit, day 42) for Placebo (A–B), 55% energy deficit + 1 mL sesame seed oil placebo per week during Phase 2 (n = 26) and Testosterone (C–D), 55% energy deficit + 200 mg testosterone enanthate per week during Phase 2 (n = 24). Images were taken with the 20× objective lens in a 15 × 10 grid. Laminin signals were stitched into one image to cover the entire specimen and analysed using Cell Profiler. Myosin heavy chain myofibres with a median intensity < 0.3 and those ≥0.3 were delineated as type II fast-twitch myofibres and type I slow-twitch myofibres, respectively. Least squares mean ± standard error in type 1 slow-twitch myofibre cross-sectional area (E), type 1 slow-twitch myofibre percent distribution (F), type II fast-twitch myofibre cross-sectional area (G), and type II fast-twitch myofibre percent distribution (H). Data were analysed using linear mixed models, adjusting for age. *Indicates a between phase difference (phase main effect).