Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women.

Daniele A Cardinale,Stéphane Bermon,Oscar Horwath,Björn Ekblom,Mikael Flockhart,Manne Godhe,Torbjörn Helge,Marcus Moberg,Angelica Lindén Hirschberg,Filip J Larsen,Jona Elings-Knutsson

doi:10.3389/fphys.2020.585490

Abstract

Background: Recently, it was shown that exogenously administered testosterone enhances endurance capacity in women. In this study, our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded.Methods: In a double-blinded, randomized, placebo-controlled trial, 48 healthy active women were randomized to 10 weeks of daily application of 10 mg of testosterone cream or placebo. Before and after the intervention, VO2 max, body composition, total hemoglobin (Hb) mass and blood volumes were assessed. Biopsies from the vastus lateralis muscle were obtained before and after the intervention to assess mitochondrial protein abundance, capillary density, capillary-to-fiber (C/F) ratio, and skeletal muscle oxidative capacity.Results: Maximal oxygen consumption per muscle mass, Hb mass, blood, plasma and red blood cell volumes, capillary density, and the abundance of mitochondrial protein levels (i.e., citrate synthase, complexes I, II, III, IV-subunit 2, IV-subunit 4, and V) were unchanged by the intervention. However, the C/F ratio, specific mitochondrial respiratory flux activating complex I and linked complex I and II, uncoupled respiration and electron transport system capacity, but not leak respiration or fat respiration, were significantly increased following testosterone administration compared to placebo.Conclusion: This study provides novel insights into physiological actions of increased testosterone exposure on key determinants of oxygen diffusion and utilization in skeletal muscle of women. Our findings show that higher skeletal muscle oxidative capacity coupled to higher C/F ratio could be major contributing factors that improve endurance performance following moderately increased testosterone exposure.

Highlights

Androgens such as testosterone are essential hormones that regulate several physiological processes, including growth, cell differentiation, metabolism, the immune system, aspects of sexual and cognitive functions, and secondary sex characteristics (Herbst and Bhasin, 2004)
It is important to note that the maintained VO2 max per kilogram muscle mass in the testosterone group was achieved by a parallel significant increase in lean mass and VO2 max whereas these variables remained unchanged in the placebo group (Table 1), as previously reported (Hirschberg et al, 2020)
Hb mass along with BV, plasma volume (PV), and red blood cell volume (RCV) were unaltered by the intervention, and no differences were detected between groups

Summary

Introduction

Androgens such as testosterone are essential hormones that regulate several physiological processes, including growth, cell differentiation, metabolism, the immune system, aspects of sexual and cognitive functions, and secondary sex characteristics (Herbst and Bhasin, 2004). Exogenous testosterone has been shown to improve sexual and cognitive functions (Davis and Wahlin-Jacobsen, 2015), lean mass, bone mineral density, and strength (Herbst and Bhasin, 2004). The apparent sex-based differences in athletic performance are largely attributed to the 10–20 times higher circulating levels of testosterone in men than in women (Handelsman et al, 2018; Hirschberg, 2020). Increasing the circulating levels of testosterone may potentially be more beneficial for improving physical performance in women than in men (Huang and Basaria, 2018). Our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded

Methods

Results

Discussion

Conclusion