From testosterone to 11-oxygenated androgens: Integrating endocrine biology, nutrition, and systemic health across the lifespan

Androgens, historically regarded as male sex hormones, are increasingly recognized as central regulators of multisystem physiology across the lifespan in both sexes. Beyond reproductive functions, classical androgens together with emerging 11-oxygenated androgens participate in the regulation of metabolic homeostasis, immune balance, cardiovascular function, musculoskeletal integrity, neurocognitive processes, and systemic aging. Advances in steroidomics, liquid chromatography–tandem mass spectrometry (LC-MS/MS), and androgen receptor biology are reshaping androgen research from a reproduction-centered perspective toward an integrated endocrine framework linking physiology, disease, nutrition, and precision medicine. This review synthesizes current understanding of androgen biosynthesis, metabolism, and receptor signaling, and summarizes their roles in reproductive disorders such as polycystic ovary syndrome, congenital adrenal hyperplasia, and late-onset hypogonadism, as well as prostate disease, metabolic and cardiovascular disorders, bone and muscle health, dermatologic conditions, and neuropsychiatric function. Therapeutic approaches-including hormone replacement therapy, selective androgen receptor modulators, enzyme-targeted interventions, and structured safety monitoring-are also discussed. An emerging frontier is the integration of nutrition and gut microbiota into androgen regulation. Micronutrients such as zinc, magnesium, and vitamin D, together with balanced macronutrient intake, anti-inflammatory dietary patterns, and probiotics, influence steroidogenesis, inflammation, insulin resistance, and androgen receptor signaling, forming a potential “nutrition–microbiota–androgen axis”. Meanwhile, LC-MS/MS-based multi-androgen profiling and early integration with AI approaches-such as ovarian-endocrine-age modeling exemplified by OvaRePred-may enable individualized interpretation and predictive analytics. Collectively, the convergence of advanced analytics, nutrition science, and AI-driven modeling is redefining androgen medicine and enabling more precise diagnosis and personalized endocrine health management.