Effects of Testosterone on Serum Concentrations, Fat-free Mass, and Physical Performance by Population: A Meta-analysis

A Meta-Analysis

Alyssa N. Varanoske; Lee M. Margolis; Stefan M. Pasiakos

Disclosures

J Endo Soc. 2020;4(9) 

In This Article

Abstract and Introduction

Abstract

Testosterone (T) administration (TA) increases serum T and fat-free mass (FFM). Although TA-mediated increases in FFM may enhance physical performance, the data are largely equivocal, which may be due to differences in study populations, the magnitude of change in serum T and FFM, or the performance metrics. This meta-analysis explored effects of TA on serum T, FFM, and performance. Associations between increases in serum T and FFM were assessed, and whether changes in serum T or FFM, study population, or the performance metrics affected performance was determined. A systematic review of double-blind randomized trials comparing TA versus placebo on serum T, FFM, and performance was performed. Data were extracted from 20 manuscripts. Effect sizes (ESs) were assessed using Hedge's g and a random effects model. Data are presented as ES (95% confidence interval). No significant correlation between changes in serum T and FFM was observed (P = .167). Greater increases in serum T, but not FFM, resulted in larger effects on performance. Larger increases in testosterone (7.26 [0.76–13.75]) and FFM (0.80 [0.20–1.41]) were observed in young males, but performance only improved in diseased (0.16 [0.05–0.28]) and older males (0.19 [0.10–0.29]). TA increased lower body (0.12 [0.07–0.18]), upper body (0.26 [0.11–0.40]), and handgrip (0.13 [0.04–0.22]) strength, lower body muscular endurance (0.38 [0.09–0.68]), and functional performance (0.20 [0.00–0.41]), but not lower body power or aerobic endurance. TA elicits increases in serum T and FFM in younger, older, and diseased males; however, the performance-enhancing effects of TA across studies were small, observed mostly in muscular strength and endurance, and only in older and diseased males.

Introduction

Chronic exposure to testosterone (T) concentrations below the normal range (9.5–31.8 nmol/L)[1] generally manifests in fat-free mass (FFM) loss and decrements in physical performance (ie, muscle strength and function).[2–5] T deficiency and associated deteriorations in FFM and physical performance are common characteristics in old[4,5] and diseased[6–11] males, but are also prevalent in healthy males exposed to stressors that suppress endogenous T synthesis, such as prolonged energy deficit, sleep deprivation, overuse, muscle unloading, injury, and spaceflight.[12–14] Thus, pharmacological restoration of normal T concentrations via exogenous T administration (TA) is now a widely accepted clinical practice in males across the population spectrum.[1,15,16]

Several meta-analyses report that, while TA increases FFM,[17–20] the performance-enhancing effects of TA are equivocal.[17,18,21] Failure to account for the magnitude of change in serum T following TA, the type of performance metric studied, and the study population (ie, young, old, and diseased males) may have contributed to the incongruent findings between TA, FFM, and physical performance in those meta-analyses.[17–20] For example, TA-mediated increases in serum T and FFM are dose-dependent,[22,23] such that higher T doses elicit greater increases in serum T and FFM. It has been suggested that FFM accrual underlies improvements in muscle strength and function, suggesting that the overall change in serum T following TA may not only predict changes in FFM but also physical performance. Furthermore, most research examining the effects of TA on physical performance only assess strength and power;[23–30] however, FFM accrual secondary to TA may benefit several other metrics of physical performance rarely assessed or included in meta-analyses, such as measures of muscle function, mobility, fatigue, and activities of daily living. The physiological responses to TA may also be affected by age (and health status). For example, eugonadal older men (60–75 years) receiving the same dose of T as eugonadal younger men (18–35 years) experienced greater absolute increases in serum T; however, the greater increase in serum T in older men than in younger men did not translate into greater FFM accretion and improvements in strength.[23] Collectively, these data suggest that the population studied must be accounted for when assessing the overall impact of TA on physical performance.

The primary objective of this systematic review and meta-analysis was to explore the effects of TA on changes in serum T, FFM, and physical performance among old, young, and diseased males. We examined associations between increases in serum T and changes in FFM following TA to determine if increases in serum T predict changes in FFM. We also aimed to determine whether changes in serum T or FFM, differences in study population, or the physical performance metrics themselves mediated the effects of TA on physical performance.

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