Dataset Information

Metabolomics of testosterone enanthate administration during severe-energy deficit.

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.

SUBMITTER: Stein JA

PROVIDER: S-EPMC9712311 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Metabolomics of testosterone enanthate administration during severe-energy deficit.

Stein Jesse A JA Karl J Philip JP Berryman Claire E CE Harris Melissa N MN Rood Jennifer C JC Pasiakos Stefan M SM Lieberman Harris R HR

Metabolomics : Official journal of the Metabolomic Society 20221130 12

<h4>Introduction</h4>Testosterone administration attenuates reductions in total body mass and lean mass during severe energy deficit (SED).<h4>Objectives</h4>This study examined the effects of testosterone administration on the serum metabolome during SED.<h4>Methods</h4>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 ...[more]

PMID: 36450940

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Project description:Introduction/purposeThe effects of testosterone on energy and substrate metabolism during energy deficit are unknown. The objective of this study was to determine the effects of weekly testosterone enanthate (TEST; 200 mg·wk -1 ) injections on energy expenditure, energy substrate oxidation, and related gene expression during 28 d of energy deficit compared with placebo (PLA).MethodsAfter a 14-d energy balance phase, healthy men were randomly assigned to TEST ( n = 24) or PLA ( n = 26) for a 28-d controlled diet- and exercise-induced energy deficit (55% below total energy needs by reducing energy intake and increasing physical activity). Whole-room indirect calorimetry and 24-h urine collections were used to measure energy expenditure and energy substrate oxidation during balance and deficit. Transcriptional regulation of energy and substrate metabolism was assessed using quantitative reverse transcription-polymerase chain reaction from rested/fasted muscle biopsy samples collected during balance and deficit.ResultsPer protocol design, 24-h energy expenditure increased ( P < 0.05) and energy intake decreased ( P < 0.05) in TEST and PLA during deficit compared with balance. Carbohydrate oxidation decreased ( P < 0.05), whereas protein and fat oxidation increased ( P < 0.05) in TEST and PLA during deficit compared with balance. Change (∆; deficit minus balance) in 24-h energy expenditure was associated with ∆activity factor ( r = 0.595), but not ∆fat-free mass ( r = 0.147). Energy sensing (PRKAB1 and TP53), mitochondria (TFAM and COXIV), fatty acid metabolism (CD36/FAT, FABP, CPT1b, and ACOX1) and storage (FASN), and amino acid metabolism (BCAT2 and BCKHDA) genes were increased ( P < 0.05) during deficit compared with balance, independent of treatment.ConclusionsThese data demonstrate that increased physical activity and not exogenous testosterone administration is the primary determinate of whole-body and skeletal muscle metabolic adaptations during diet- and exercise-induced energy deficit.

Project description:BackgroundSevere 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.ObjectiveTo determine whether testosterone supplementation during severe energy deficit influences fasting and postprandial ghrelin concentrations and appetite.Design and methodsSecondary 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.ResultsFasting 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.ConclusionsTestosterone 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 registrationwww.clinicaltrials.gov NCT02734238 (registered 12 April 2016).

Project description:Abstract BACKGROUND: In men, obesity is often associated with low testosterone (T) levels, but information is limited as to how body weight affects the pharmacokinetic profile or dosing of testosterone therapy (TTh) in men with T deficiency. Historically, men with body mass index (BMI) >32.4 kg/m2 required higher doses of T 2% gel to achieve physiological T levels than men with BMI ≤29.1 or 29.2–32.4 kg/m2.(1) In a phase 3 trial (N=150) of subcutaneous (SC) testosterone enanthate (TE) administered weekly, concentration-guided dosing raised T levels to within physiological range in 92.7% of patients.(2) Here, we report a post hoc analysis evaluating the association between body weight and serum T levels attained with SC TE. Methods: SC TE was evaluated in an open-label, single-arm, dose-blinded, 52-week phase 3 trial (NCT02159469). Patients self-administered 75 mg SC TE weekly during the titration phase; blinded dose-adjustments in 25 mg increments occurred at pre-defined time points beyond the sixth dose. The primary endpoint of this study was the percentage of patients achieving an average serum T concentration (Cavg0-168h) of 300 to 1,100 ng/dL at week 12. For this post hoc analysis, a linear regression model with weight and dose as independent variables was used to assess differences in mean minimum T concentration (Cmin) and Cavg0-168h at week 12. Results: For this analysis, 137 patients were included. Doses were 50 mg (n=25), 75 mg (n=93), and 100 mg (n=19). The mean weight was 84.4 kg, 102.2 kg, and 112.0 kg for the 50 mg, 75 mg, and 100 mg dose groups, respectively (range, 49.9–146.5 kg). The dose-normalized T Cmin was 9.2 ng/dL, 5.7 ng/dL, and 4.3 ng/dL per 1 mg of SC TE for the 50 mg, 75 mg, and 100 mg groups, respectively. The dose-normalized T Cavg0-168h was 12.0 ng/dL, 7.2 ng/dL, and 5.7 ng/dL per 1 mg of SC TE. In an overall linear regression model, 48.2% (P<0.0001) and 55.0% (P<0.0001) of the total variance in Cmin and Cavg0-168h, respectively, can be predicted from the independent weight and dose variables. Conclusion: Our results show an inverse relationship between body weight and T exposure. Men with higher mean body weights required higher doses of SC TE to achieve physiologic T levels compared with men with lower mean body weights. The available doses provide effective options to reach target exposures. These findings highlight the impact of weight and dose selection on SC TE exposure. References: (1) Dobs et al., J Sex Med 2014;11:857–864; (2) Kaminetsky et al., J Urol. 2019;201:587–94.

Project description:The objective of this study was to determine metabolic and physiological differences between males with low testosterone (LT) versus those with normal testosterone (NT) following a period of severe energy deficit. In this secondary analysis, 68 male US Marines (mean ± SD, 24.6 ± 2.4 y) were dichotomized by testosterone concentration (< or ≥ 10.5 nmol/L as determined from a single blood sample collected between 0600-0630 after an 8-10 h overnight fast by automated immunoassay) following 7 days of near complete starvation (~300 kcal consumed/d, ~85% energy deficit) during Survival, Evasion, Resistance, and Escape (SERE) training. Dietary intake was assessed before (PRE) SERE. Body composition (dual-energy x-ray absorptiometry and peripheral quantitative computed tomography) and whole-body protein turnover (15 N alanine) were assessed before (PRE) and after (POST) SERE. Mean testosterone concentrations decreased PRE (17.5 ± 4.7 nmol/L) to POST (9.8 ± 4.0 nmol/L, p < 0.0001). When volunteers were dichotomized by POST testosterone concentrations [NT (n = 24) 14.1 ± 3.4 vs. LT (n = 44): 7.5 ± 1.8 nmol/L, p < 0.0001], PRE BMI, total fat mass, trunk fat mass, and testosterone were greater and the diet quality score and total carbohydrate intake were lower in NT compared to LT (p ≤ 0.05). LT lost more fat-free mass and less fat mass, particularly in the trunk region, compared to NT following SERE (p-interaction≤0.044). Whole-body protein synthesis, net balance, and flux decreased and whole-body protein breakdown increased from PRE to POST in both groups (p-time ≤0.025). Following short-term, severe energy deficit, Marines who exhibited low testosterone had greater fat-free mass loss than those who maintained normal testosterone concentrations. Altering body composition and dietary strategies prior to physical training that elicits severe energy deficit may provide an opportunity to attenuate post-training decrements in testosterone and its associated effects (e.g., loss of lean mass, performance declines, fatigue).

Project description:The loss of fat-free mass (FFM) caused by very-low-calorie diets (VLCD) can be attenuated by exercise. The aim of this study was to determine the role played by exercise and dietary protein content in preserving the lean mass and performance of exercised and non-exercised muscles, during a short period of extreme energy deficit (~23 MJ deficit/day). Fifteen overweight men underwent three consecutive experimental phases: baseline assessment (PRE), followed by 4 days of caloric restriction and exercise (CRE) and then 3 days on a control diet combined with reduced exercise (CD). During CRE, the participants ingested a VLCD and performed 45 min of one-arm cranking followed by 8 h walking each day. The VLCD consisted of 0.8 g/kg body weight/day of either whey protein (PRO, n = 8) or sucrose (SU, n = 7). FFM was reduced after CRE (P < 0.001), with the legs and the exercised arm losing proportionally less FFM than the control arm [57% (P < 0.05) and 29% (P = 0.05), respectively]. Performance during leg pedaling, as reflected by the peak oxygen uptake and power output (Wpeak), was reduced after CRE by 15 and 12%, respectively (P < 0.05), and recovered only partially after CD. The deterioration of cycling performance was more pronounced in the whey protein than sucrose group (P < 0.05). Wpeak during arm cranking was unchanged in the control arm, but improved in the contralateral arm by arm cranking. There was a linear relationship between the reduction in whole-body FFM between PRE and CRE and the changes in the cortisol/free testosterone ratio (C/FT), serum isoleucine, leucine, tryptophan, valine, BCAA, and EAA (r = -0.54 to -0.71, respectively, P < 0.05). C/FT tended to be higher in the PRO than the SU group following CRE (P = 0.06). In conclusion, concomitant low-intensity exercise such as walking or arm cranking even during an extreme energy deficit results in remarkable preservation of lean mass. The intake of proteins alone may be associated with greater cortisol/free testosterone ratio and is not better than the ingestion of only carbohydrates for preserving FFM and muscle performance in interventions of short duration.

Dataset Information

Metabolomics of testosterone enanthate administration during severe-energy deficit.

Introduction

Objectives

Methods

Results

Conclusion

Publications

Metabolomics of testosterone enanthate administration during severe-energy deficit.

Similar Datasets

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