Sleep Disorders and Male Infertility: Integrated Mechanisms and Precision Therapeutic Strategies

Male factor infertility accounts for nearly half of infertility cases worldwide, yet modifiable lifestyle-related risk factors remain insufficiently integrated into andrological research and clinical practice. Sleep disorders have emerged as an increasingly important but underrecognized determinant of male reproductive health, with growing evidence linking disturbed sleep to impaired spermatogenesis and gonadal dysfunction.

This review synthesizes current evidence on the association between sleep disorders and male infertility, identifies key mechanistic pathways underlying sleep-related reproductive impairment, and proposes an integrated pathophysiological framework to inform precision phenotyping and targeted interventions.

A narrative review was conducted integrating epidemiological, experimental, and clinical studies addressing sleep disorders and male reproductive outcomes, with emphasis on oxidative stress, inflammation, endocrine and metabolic dysregulation, circadian rhythm disruption, epigenetic regulation, and related therapeutic evidence.

Evidence indicates that sleep disorders compromise male fertility through converging mechanisms. Excessive reactive oxygen species (ROS) generation and chronic inflammatory activation directly damage testicular tissue and sperm DNA. Disruption of the hypothalamic-pituitary-gonadal (HPG) axis impairs testosterone synthesis and hormonal rhythmicity essential for spermatogenesis, while metabolic-endocrine dysregulation further exacerbates gonadal dysfunction. Circadian misalignment induces epigenetic reprogramming in spermatozoa, potentially mediating intergenerational reproductive effects. Integrating these findings, we propose the sleep-oxidative stress-circadian disruption-epigenetics-spermatogenesis axis as a unifying model linking sleep disorders to male infertility. Multimodal interventions, including continuous positive airway pressure (CPAP), antioxidant therapy, endocrine and metabolic modulation, circadian rhythm restoration, and cognitive-behavioral approaches, demonstrate potential to mitigate sleep-related reproductive impairment.

Sleep disorders represent clinically actionable contributors to male infertility. An integrated framework incorporating oxidative stress, circadian biology, endocrine regulation, and epigenetic inheritance supports a precision andrology approach. Future directions include epigenetic biomarker - guided stratification, artificial intelligence (AI) - assisted sleep assessment, and longitudinal follow-up to optimize individualized management of sleep-related male reproductive dysfunction.