Sleep apnea risk in transmasculine individuals on testosterone therapy: A population-based cohort study

Importance: Testosterone affects airway anatomy and respiratory control, potentially increasing the risk of obstructive and central sleep apnea. While findings in cisgender men are mixed, studies of women with hyperandrogenic conditions, such as polycystic ovary syndrome, consistently demonstrate elevated prevalence. Given that sleep apnea is a major public health concern, its relationship to testosterone in transmasculine individuals warrants investigation. Objective: This study aims to assess whether testosterone therapy is associated with increased risk of obstructive and central sleep apnea in transmasculine individuals. Methods: We conducted a retrospective cohort study using TriNetX, a U.S. health record database of over 120 million individuals, from 2004-2024. Transmasculine individuals were identified via gender incongruence diagnoses and documented testosterone use, excluding those with prior sleep apnea. The index date for follow-up was three months after testosterone initiation. Risk of new sleep apnea diagnosis among transmasculine cohorts was compared to cisgender male and female counterparts. Propensity score matching adjusted for body mass index, smoking, and number of ambulatory healthcare visits, given clinical monitoring differences. Outcomes, including obstructive and central sleep apnea, were assessed with Kaplan-Meier curves and Cox proportional hazards models. Results: Among 22,745 transmasculine individuals after propensity score matching, overall sleep apnea risk was significantly higher than in cisgender females (HR: 3.01; 95% CI: 2.70-3.36) and males (HR: 1.64; CI: 1.49-1.81). Obstructive sleep apnea risk was elevated compared to cisgender females (HR: 3.25; CI: 2.88-3.67) and males (HR: 1.74; CI: 1.57-1.95). Central sleep apnea risk was substantially higher than in cisgender females (HR: 7.34; CI: 2.52-21.41) and mildly higher than in males (HR: 2.66; CI: 1.31-5.40). Conclusions and Relevance: Testosterone therapy is associated with increased risk of sleep apnea in transmasculine individuals. This highlights the need for screening and underscores the importance of longitudinal studies using objective sleep measures to clarify mechanisms and clinical implications.