Endogenous androgens, physical and cognitive function in healthy midlife men: A systematic review

Objective: In men, androgens begin to decline during midlife, yet their functional implications in this period remain unclear. This review synthesizes evidence linking androgens with physical and cognitive performance in healthy middle-aged men. Methods: This systematic review followed PRISMA 2020 guidelines. PubMed, Scopus, and Embase were searched (2010–2026) for observational studies assessing androgens and objective physical or cognitive outcomes in men aged 45–64 years or broader midlife-inclusive samples. Data extraction and quality appraisal were performed independently by two reviewers. Results: Sixteen studies were included. Small positive associations with physical performance were observed mainly between free/bioavailable testosterone and grip-strength, with less consistent mobility findings. Midlife-focused analyses showed more consistent associations than broader age-range studies. Cognitive findings varied across domains and assessment tools. Visuospatial abilities showed the most consistent associations with testosterone, whereas verbal and episodic memory demonstrated mixed results. Dehydroepiandrosterone-sulfate showed small consistent associations with executive function and processing speed. Heterogeneity in assays and measures limited comparability. Conclusions: Subtle associations between endogenous-androgens and functional performance can be detected in healthy middle-aged men. However, these relationships are small, domain-specific, and obscured by methodological variability. Sensitive performance assessments and standardized hormonal evaluation are needed to clarify whether androgen profiles identify early functional vulnerability.