Biological Sex and Chronic Rhinosinusitis Diagnosis and Biomarkers.

Importance: The inflammation-modulating properties of sex hormones provide a pathophysiological basis for anticipating sex-based differences in chronic rhinosinusitis (CRS), but the role of biological sex has not been thoroughly studied. Objectives: To investigate sex differences in CRS diagnosis and biomarkers. Design, Setting, and Participants: This cross-sectional study used data from the All of Us Research Program, a large national dataset of US adults, collected from partner health care organizations including academic medical centers, Veterans Affairs facilities, and community health centers. From May 2018 to October 2023, a total of 393 596 participants with electronic health records were considered for inclusion; those with incomplete data were excluded. Data analysis was conducted from April to September 2025. Exposures: Participant sex was the primary exposure, and covariates included demographics, socioeconomic status, risk factors, and comorbidities. Main Outcomes and Measures: CRS diagnosis, stratified into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), and CRS biomarkers. Results: The analysis included 258 245 participants, of whom 38.4% were male and 61.6% were female and most (57.3%) were 50 years or older. After controlling for covariates, female sex was associated with an increased odds of CRSsNP among those younger than 60 years (odds ratio [OR], 1.44; CI with Holm-Bonferroni correction [CIH-B], 1.35 to 1.54) and 60 years or older (OR, 1.32; CIH-B, 1.23 to 1.40), but a lower odds of CRSwNP (OR, 0.63; CIH-B, 0.52-0.76) compared to males. Compared to male participants, female participants had a lower concentration of serum eosinophils (β, -0.35; CIH-B, -0.44 to -0.25) and IgE (β, -99.73; CIH-B, -190.49 to -8.96) among participants with CRSsNP after controlling for covariates, as well as lower eosinophils among participants with CRSwNP (β, -0.41; CIH-B, -0.80 to -0.01). Analyzing CRS prevalence by age group revealed a downtrend among female participants 60 years or older, despite an upward trend at younger age groups, with regression analysis demonstrating a negative interaction effect between female sex and age 60 years or older with odds of CRSsNP (OR, 0.91; CIH-B, 0.84 to 0.99). Conclusions and Relevance: This cross-sectional study found that female sex was associated with a higher odds of CRSsNP, but a lower odds of CRSwNP compared to males. Biomarker analysis indicated a possible female disposition for nontype 2 inflammation.