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Exercise & healthspan
Research brief

Testosterone and muscle: molecular links without mass or strength gains in men 18–80

In 81 healthy men aged 18–80, free testosterone was strongly linked to the muscle transcriptome, but neither free nor total testosterone was linked to muscle mass or strength. [1]

Automatic summary · not editorially reviewed

The key findings

  1. Eighty-one healthy males aged 18–80 underwent phenotypic assessment including body composition, muscle morphology, strength and vastus lateralis biopsies. [1]

  2. Free, but not total, testosterone was strongly associated with the muscle transcriptome, while neither fraction was associated with muscle mass or strength. [1]

  3. In primary myocytes, testosterone increased androgen receptor abundance and nuclear localisation and enriched protein translation pathways. [1]

The source at a glance

Study type / format
Observational study with primary myocyte experiments (abstract).
Population / context
81 healthy males aged 18–80 years.
Summary based on
Study abstract
Publication status
Preprint · peer-review status not confirmed
Original publication
October 17, 2026

81 men aged 18–80 and muscle measures

The study asked whether endogenous testosterone levels are associated with skeletal muscle phenotype across adult life and whether ageing changes this relationship. Eighty-one healthy males aged 18–80 underwent a broad phenotypic assessment. Body composition and muscle morphology were measured with dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Muscle strength was estimated as leg press one-repetition maximum. Biopsies of the vastus lateralis muscle were used to assess fibre type, sequence the transcriptome and establish primary myocytes.

Supporting source [1]

Free testosterone tracked the transcriptome, not mass or strength

Ageing was associated with lower free testosterone, lower muscle mass and strength, altered type IIa fibre characteristics and widespread transcriptional changes in skeletal muscle. Free, but not total, testosterone was strongly associated with the muscle transcriptome. However, neither fraction was associated with muscle mass or strength. In primary myocytes, testosterone increased androgen receptor abundance and nuclear localisation and enriched pathways involved in protein translation.

Supporting source [1]

Cell lines from young and older donors compared

Primary myocytes came from young donors (n=5) and older donors (n=7). These cell lines were cultured and compared under control and testosterone-treated conditions for cellular phenotype. The authors conclude that testosterone is biologically active in male skeletal muscle, with its free fraction strongly associated with the transcriptome, but that these molecular effects do not translate into differences in muscle mass or strength. They suggest testosterone may mainly help establish the male muscle phenotype during puberty and play a more ancillary role in adult muscle.

Supporting source [1]

How to interpret this

Abstract only; the full text was not reviewed. This is an observational study of 81 healthy men, so associations are not causes. The myocyte experiments used cell lines from 5 young and 7 older donors and do not show effects on human muscle mass, strength or lifespan.

Based on the study abstract; the full paper, tables and supplementary data were not reviewed.

Source & supporting passages

[1]
Molecular responsiveness to testosterone is uncoupled from skeletal muscle mass and strength in males aged 18 - 80 years

Williams RM, Soria M, Critchlow A, Van Belleghem K, Engman V, Garnham A, Hiam D, Wadley GD, Lamon S. · europepmc.org · October 17, 2026

Read the quoted passagesIn the language of the original source
  1. Finding 1 ↑

    Eighty-one healthy males aged 18-80 underwent comprehensive
  2. Finding 2 ↑

    neither fraction was associated with muscle mass
  3. Finding 3 ↑

    testosterone increased androgen receptor abundance and nuclear

AI-assisted summary with linked source passages. No independent editorial or clinical review.

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