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 testosterone 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.