Psychological stress is increasingly investigated as a potentially modifiable factor in male infertility, in part through oxidative stress. This narrative review synthesizes mechanistic and translational evidence linking stress-related neuroendocrine activation and coping behaviors with redox imbalance in the male reproductive tract. Chronic activation of the hypothalamic-pituitary-adrenal axis and sympathetic outflow elevates glucocorticoids and catecholamines. In controlled animal stress paradigms, this is accompanied by suppression of the hypothalamic-pituitary-gonadal axis and by immune and metabolic changes that favor reactive oxygen species generation. The resulting oxidative stress may reduce Leydig cell steroidogenesis, impair testicular and epididymal function, and induce lipid peroxidation, mitochondrial dysfunction, and sperm DNA fragmentation. In such models, these lesions, together with apoptosis of germ and supporting cells, are associated with lower sperm concentration, reduced motility, compromised viability, and diminished fertilizing potential. Overall, preclinical animal studies using defined stress paradigms provide experimental evidence consistent with causal effects of stress on oxidative injury and reproductive impairment in preclinical settings. Human studies linking perceived stress, anxiety/depression, and disturbed sleep to adverse semen parameters and oxidative biomarkers are summarized. However, the human evidence is predominantly associative, and the available studies are cross sectional and remain vulnerable to residual confounding and reverse causality. Potential effect modifiers, including smoking, alcohol use, and circadian disruption, are also discussed as contributors to heterogeneity across clinical studies. Standardized assessment of stress biology and redox status, longitudinal designs aligned with spermatogenic timing, and well-powered intervention trials are needed to define dose-response relationships and support individualized prevention and care.
Biomedicines. 2026 Jan 23*** epublish ***
Aris Kaltsas, Stamatis Papaharitou, Fotios Dimitriadis, Michael Chrisofos, Nikolaos Sofikitis
Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece., Andrology Laboratory and Sperm Bank, 54622 Thessaloniki, Greece., Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece., Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.