Sex-Associated Differences in Age-Related Sensorineural Hearing Loss: Why Are Men More Vulnerable?

Age-related hearing loss is a progressive bilateral sensorineural loss that increases steeply with age, contributing to communication disabilities and social isolation, impacting healthy aging. Across diverse cohorts, men tend to develop earlier and more severe high-frequency threshold elevations than age-matched women. This male disadvantage is partly explained by gender-related lifetime exposure (e.g., occupational noise, smoking), likely reflecting interactions with biological sex factors, including steroid signaling and mitochondrial susceptibility. Sex differences in cochlear physiology are detectable from infancy, including larger otoacoustic emissions in female newborns, supporting developmental endocrine influences. Adult men usually exhibit earlier and steeper high-frequency declines. Conversely, studies in menopausal women have indicated heterogeneity rather than a uniform female inflection point. Mechanistic studies have demonstrated inner-ear estrogen receptor expression and context-dependent otoprotection. However, human epidemiology does not support uniform auditory benefits from menopausal hormone therapy; rather, long-term oral estrogen or estrogen plus progestogen use may increase the risk of hearing loss. Evidence for androgen pathways is emerging, albeit limited. In older men, higher serum testosterone, but not dehydroepiandrosterone sulfate, is associated with lower odds of high-frequency hearing loss. The precise mechanisms and clinical effects of exogenous hormone therapies on auditory aging remain uncertain. This review synthesizes current evidence using a life-course "multi-hit" framework. Rather than pointing to a single biological driver, we describe how innate susceptibilities such as the aging endocrine axis and mitochondrial variation interact with male-predominant ototoxic exposure and cardiometabolic comorbidities to shape auditory dimorphisms. Addressing current knowledge gaps requires sex-stratified longitudinal research integrating precise endocrine profiling with functional auditory outcomes. Clinically, although endocrine pathways are not yet therapeutic targets, understanding this multidimensional vulnerability highlights the utility of risk-stratified screening. Incorporating proactive hearing assessment into routine evaluations of aging men, particularly those with late-onset hypogonadism, can facilitate early detection, timely rehabilitation, and possible downstream cognitive benefit.