Metabolomics of testosterone enanthate administration during severe-energy deficit

Abstract

Abstract Introduction Testosterone administration attenuates reductions in total body mass and lean mass during severe energy deficit (SED). Objectives This study examined the effects of testosterone administration on the serum metabolome during SED. Methods In a double-blind, placebo-controlled clinical trial, non-obese men were randomized to receive 200-mg testosterone enanthate/wk (TEST) (n = 24) or placebo (PLA) (n = 26) during a 28-d inpatient, severe exercise- and diet-induced energy deficit. This study consisted of three consecutive phases. Participants were free-living and provided a eucaloric diet for 14-d during Phase 1. During Phase 2, participants were admitted to an inpatient unit, randomized to receive testosterone or placebo, and underwent SED for 28-d. During Phase 3, participants returned to their pre-study diet and physical activity habits. Untargeted metabolite profiling was conducted on serum samples collected during each phase. Body composition was measured using dual-energy X-ray absorptiometry after 11-d of Phase 1 and after 25-d of Phase 2 to determine changes in fat and lean mass. Results TEST had higher (Benjamini–Hochberg adjusted, q < 0.05) androgenic steroid and acylcarnitine, and lower (q < 0.05) amino acid metabolites after SED compared to PLA. Metabolomic differences were reversed by Phase 3. Changes in lean mass were associated (Bonferroni-adjusted, p < 0.05) with changes in androgenic steroid metabolites (r = 0.42–0.70), acylcarnitines (r = 0.37–0.44), and amino acid metabolites (r = − 0.36–− 0.37). Changes in fat mass were associated (p < 0.05) with changes in acylcarnitines (r = − 0.46–− 0.49) and changes in urea cycle metabolites (r = 0.60–0.62). Conclusion Testosterone administration altered androgenic steroid, acylcarnitine, and amino acid metabolites, which were associated with changes in body composition during SED.