Association between obstructive sleep apnea and sex hormones in U.S. adult males: a population-based study

Abstract Background The relationship between obstructive sleep apnea (OSA) and comprehensive sex hormone profiles, including free testosterone, in men remains unclear. Aim This study aimed to explore the independent association between OSA risk and a panel of sex hormone indices after adjusting for obesity. Methods We conducted a cross-sectional analysis of 2218 adult males from the National Health and Nutrition Examination Survey 2015–2016. OSA was assessed using an adjusted multivariable apnea prediction index and categorized into tertiles. Sex hormones were measured via isotope dilution liquid chromatography–tandem mass spectrometry and immunoassays. Associations were examined using weighted multivariable linear and logistic regression, adjusted for demographics, and clinical factors. Restricted cubic spline and mediation analyses were performed to assess nonlinearity and the mediating role of sex hormone-binding globulin. Outcomes Primary outcomes were total testosterone, sex hormone-binding globulin, and free androgen index; secondary outcomes included estradiol, total testosterone/estradiol ratio, and testosterone deficiency prevalence. Results In fully adjusted models, higher OSA risk was significantly associated with lower ln(total testosterone) (β = -0.23, 95% CI, -0.40 to -0.06) and ln(sex hormone-binding globulin) (β = -0.49, 95% CI, -0.66 to -0.31). No significant association was found with free testosterone or estradiol. Testosterone deficiency prevalence was markedly higher in the high-risk OSA group (43.83%) versus the low-risk group (12.70%), with a borderline significant association for the continuous OSA score (OR = 3.85, P = .04). Sex hormone-binding globulin mediated a substantial proportion of the OSA-total testosterone relationship (P .001). Clinical Implications Routine screening for sex hormone-binding globulin in obese OSA patients may help prevent misdiagnosis of hypogonadism and guide targeted intervention. Strengths and Limitations Strengths include a nationally representative sample and comprehensive hormone profiling; limitations include the cross-sectional design and subjective OSA assessment. Conclusion OSA risk is associated with a hormonal profile of low total testosterone and sex hormone-binding globulin but preserved free testosterone, a relationship strongly moderated by body mass index.