Do androgens support libido, mood/energy, and maintenance of lean body mass in women?

The role of androgens in female physiology is increasingly recognized, particularly concerning sexual health and muscle maintenance. While often characterized as "male hormones," androgens are essential for female metabolic and psychological health, though their influence varies across different systems.

Clinical evidence for libido and sexual health

Androgens are vital modulators of female sexual desire, primarily through their action on the brain’s motivation centers.

• Hypoactive Sexual Desire Disorder (HSDD): High-level evidence from meta-analyses of randomized controlled trials (RCTs) confirms that physiological-dose testosterone therapy significantly improves sexual desire and increases satisfying sexual events in postmenopausal women with HSDD.
• Clinical Nuance: There is no universal "female androgen deficiency" syndrome. Serum testosterone levels do not reliably predict sexual dysfunction, as many women with low levels experience no symptoms. Consequently, treatment focuses on clinical symptoms rather than specific laboratory targets.
• Safety: The most common side effects of physiological androgen therapy are mild androgenic effects, such as acne and increased facial or body hair (hirsutism).

Maintenance of lean body mass

Androgens play a direct role in maintaining and repairing muscle tissue in women, regardless of age.

• Muscle Protein Synthesis: RCTs demonstrate that testosterone exposure acutely increases muscle protein synthesis in both pre- and postmenopausal women.
• Tissue Preservation: Androgens bind to receptors in skeletal muscle to activate anabolic signaling (mTORC1) and reduce protein breakdown. They also enhance the function of satellite cells, which are necessary for muscle fiber repair and long-term maintenance of lean mass.
• Functional Impact: Low-dose testosterone has been shown to improve muscle oxidative capacity and VO₂max in healthy, active women.

Impact on mood, energy, and fatigue

The relationship between androgens and psychological well-being is more complex and less clearly established than their role in sexual health.

• Vitality and Mood: While observational studies and subjective patient reports frequently link androgen replacement to improved energy (with some studies showing improvements in over 80% of participants), these results are not consistently replicated in gold-standard RCTs.
• Fatigue: Large-scale cohort studies and Mendelian randomization analyses have failed to find a robust causal link between endogenous testosterone levels and clinical fatigue. Fatigue in women is typically multifactorial, involving metabolic, sleep, and psychological factors.
• Depression: Rigorous trials have shown that testosterone therapy does not function as a reliable antidepressant in women, even when low levels are present.

Mechanistic explanations

• Neural Circuitry: Androgens enhance libido by modulating mesolimbic dopaminergic reward circuits (VTA to Nucleus Accumbens). This increases the "incentive salience" or "wanting" component of sexual stimuli.
• Molecular Anabolism: In muscle tissue, androgens stimulate protein accretion by increasing the fractional synthesis rate and decreasing the ubiquitin–proteasome pathway, which is responsible for protein degradation.
• Energy Metabolism: Androgens may influence mitochondrial respiration and ATP production, providing a biological framework for their perceived effects on vitality, though this is still an emerging area of research in humans.

Bottom line

Androgens are essential for maintaining lean body mass and driving sexual desire in women; however, their role in energy and mood is less certain. While physiological replacement can effectively treat HSDD in postmenopausal women, low androgen levels are not a definitive cause of fatigue, which often requires a broader clinical investigation.