Testosterone Administration Does Not Affect The Muscle Metabolome During Severe Energy Deficit And Subsequent Recovery

PURPOSE: Administering testosterone (T) during severe energy deficit preserves fat-free mass (FFM). Muscle metabolic adaptations underlying this effect and whether they persist during recovery are unclear. This study aimed to determine the effect of T administration on the muscle metabolome during and in recovery from severe exercise-induced energy deficit (DEF). METHODS: After a 7-d baseline, 32 men (mean ± SD, 26 ± 4 y) received a single intramuscular injection of T undecanoate (750 mg; TEST) or placebo (PLA) before completing four consecutive 5-d cycles of low stress (2 d; ~1230 kcal/d DEF; 8 h sleep) and high stress (3 d; ~2800 kcal/d DEF; 4 h sleep) followed by a 20-d recovery. Participants maintained habitual activity during baseline and recovery and energy and macronutrient intake was constant across phases. Circulating T and body composition (4-compartment model) were measured in the rested, fasted state, before (PRE) and after the 20-d DEF (POST) and recovery (REC). Muscle biopsies (vastus lateralis) were collected in rested, fasted conditions at each timepoint for global metabolite profiling of energy, carbohydrate, lipid, and protein metabolites (Metabolon, Inc; Benjamini Hochberg method to control false discovery). RESULTS: Total T was 6.7 ± 2.6 (mean ± SE) nmol/L higher (P < 0.05) in TEST than PLA at POST. FFM decreased (P < 0.05) 2.3 ± 1.0 kg from PRE to POST in PLA but not TEST. Total T and FFM were similar (P > 0.05) between groups by REC. Of 588 identified metabolites, 242 changed (P < 0.05) from PRE to POST independent of treatment, and 136 of those were similar (P > 0.05) to PRE by REC. Only 27% of branched chain amino acid (BCAA) metabolites increased (P < 0.05) from PRE to POST independent of treatment. PRE to POST changes were primarily related to lipid (46% of lipid metabolites) and energy (67% of energy metabolites) metabolism, including increases (P < 0.05) in 64% of acyl carnitines and 50% of TCA cycle metabolites. CONCLUSIONS: T administration before DEF did not alter BCAA metabolite abundance at POST or REC. These findings suggest that the preservation of FFM in TEST cannot be explained by a sparing of muscle protein from substrate oxidation pathways. The observed muscle metabolic adaptations are instead driven primarily by DEF and are not fully restored during recovery. Supported by USAMRDC. Authors' views not official US Army or DoD policy.