Age and Sex Matter: Phenotypic Heterogeneity, Diagnostic Gaps, and Screening Tool Performance in Obstructive Sleep...

Background: Obstructive sleep apnea (OSA) is a highly prevalent and heterogeneous sleep disorder. This study aimed to investigate age- and sex-specific phenotypes of OSA in a large clinical cohort, with special emphasis on the effects of aging and menopause on disease severity, hypoxemic component, symptom expression, comorbidities, and screening tool performance. Methods: A retrospective cross-sectional analysis was conducted on 3736 patients with confirmed OSA referred to a tertiary sleep clinic in Greece between 2013 and 2023. Participants were stratified by age and sex. Women were further classified as pre- and post-menopausal using age as a proxy. Clinical characteristics, comorbidities, questionnaire data and polysomnographic indices were analyzed using parametric and non-parametric statistical methods. Results: OSA severity peaked in middle age and remained high in older adults, while nocturnal hypoxemia and cardiometabolic comorbidities worsened with age. Women presented at an older age and with higher body mass index but lower Apnea Hypopnea Index (AHI) compared to men, yet experienced significantly longer hypoxemia and more severe insomnia. Women over 45 years exhibited a markedly more severe and hypoxic phenotype and substantially higher rates of comorbidities. Screening tool performance varied across subgroups: STOP-BANG was the most consistent, while symptom-based tools performed poorly in young women and elderly patients. Conclusions: OSA is a dynamic dependent disorder with distinct phenotypes across the lifespan. Current screening strategies fail to adequately capture these variations, particularly in women and older adults. A personalized, sex- and age-specific approach to OSA diagnosis and management is essential to reduce underdiagnosis and improve outcomes.