Biological sex-dependent differences in postural orthostatic tachycardia syndrome

Abstract Aims This prospective, cross-sectional study aimed to identify sex-based differences in diagnostic and symptom experiences in postural orthostatic tachycardia syndrome (POTS). Methods and results Data from participants ≥ 16 years with physician-confirmed POTS enrolled in the Australian POTS registry between 1 May 2021 and 30 April 2024 were analysed. Health-related quality of life was assessed using the EuroQol 5 Dimension tool. Composite autonomic symptom score (COMPASS-31) assessed autonomic symptom burden. Self-reported sociodemographic and diagnostic journey data informed diagnostic experiences. In total, 452 females (mean age 31.4 ± 11.4 years) and 48 males (mean age 31.1 ± 14.6 years) were included. Females experienced worse autonomic symptom burden (total COMPASS-31; 50.5 ± 13.7 vs. 42.4 ± 16.4 for men; P 0.001). Both sexes interacted with an equivocal number of doctors (P = 0.763) and emergency departments (P = 0.830) before diagnosis. Females had significantly longer diagnostic delays than men (7.0 ± 8.6 vs. 3.8 ± 5.4 years; P = 0.010) and were 1.2.7 times more likely to experience ≥10 years of diagnostic delay (95% CI; 1.1–6.6). Despite the diagnostic latency and worse symptom burden, females reported similar, anxiety, depression, and health-related quality of life to men (global health rating where ‘100’ = full health; females, 46.2 ± 20.4 vs. males, 43.7 ± 23.6; P = 0.485). Conclusion Females and males with POTS experience significant differences in autonomic symptom burden and diagnostic delay. These differences do not seem to arise from sex-based variations in health-seeking behaviour or symptom reporting but rather indicate the influence of clinician-dependent factors. Further research is needed to explore how clinician attitudes may impact sex-dependent differences in diagnosis and treatment outcomes for those with POTS. Registration ANZCTR:12621001034820