Can low testosterone in women reduce muscle maintenance and energy?

Testosterone plays a nuanced role in female physiology, particularly regarding skeletal muscle homeostasis and subjective vitality. While its biological influence is clear, its clinical utility for addressing fatigue and muscle building in women is highly specific.

Molecular mechanisms of muscle maintenance

• Anabolic signaling: Skeletal muscle maintenance is driven by the PI3K-Akt-mTORC1 cascade, which stimulates protein synthesis and suppresses catabolic pathways, including FoxO-dependent transcription of E3 ubiquitin ligases like MuRF-1 and Atrogin-1.
• Androgen receptor action: In females, low bioavailable testosterone limits the nuclear translocation and localization of androgen receptors (nAR) in skeletal muscle. Evidence from female myocyte models indicates that nAR localization modulates hypertrophy and muscle mass independently of canonical Akt/mTOR signaling.

Muscle hypertrophy and training adaptations

• Total vs. free testosterone: Within normal female ranges, baseline total testosterone does not correlate with baseline skeletal muscle mass or training-induced strength gains.
• Bioavailable influence: Free or bioavailable testosterone (or a higher free androgen index) shows a modest positive association with relative hypertrophic outcomes. Furthermore, exogenous testosterone administration in women significantly increases lean body mass and type II muscle fiber hypertrophy.

Clinical energy and fatigue

• Therapeutic limitations: Double-blind, placebo-controlled trials show that testosterone replacement does not outperform placebo for general or cognitive fatigue, including in surgically menopausal cohorts or those with antidepressant-resistant depression.
• Clinical guidelines: Major endocrine consensus guidelines advise against diagnosing "androgen deficiency" in women due to a lack of normative reference ranges. The only established, evidence-based indication for female transdermal testosterone therapy is Hypoactive Sexual Desire Disorder (HSDD).

Bottom line

• Low bioavailable testosterone can modestly limit female muscle hypertrophy potential and nuclear androgen receptor signaling. However, testosterone levels are not a reliable clinical explanation for fatigue, and testosterone therapy is not indicated or effective for treating low energy in women.