Abstract
BACKGROUND: Transgender persons have been reported to experience excess mortality, but evidence is dominated by Western cohorts and seldom addresses familial confounding. METHODS: We conducted a nationwide, retrospective cohort study using two prespecified comparison designs: matched population controls (1:4, matched on legal sex and birth date) and within-family cisgender sibling comparisons. Transgender persons were identified by ≥2 psychiatrist-recorded gender identity disorder diagnoses during 2001-2021; cohort entry required age ≥6 years. Participants were followed until death or December 31, 2022. We compared all-cause, external-cause (suicide and accidents), and internal-cause mortality using Cox regression adjusted for sociodemographics and medical comorbidity. FINDINGS: Among 3906 transgender persons (mean age 24.6 years; 70.6% with a male legal sex) and 15,624 controls (mean follow-up 9.5 years), psychiatric conditions were markedly over-represented in the transgender cohort (e.g., depressive disorders 40.8% vs 5.7%). Adjusted hazard ratios were 1.40 (95% confidence interval 1.06-1.84) for all-cause mortality, 2.03 (1.39-2.96) for external causes, and 4.07 (2.52-6.59) for suicides; accidents (0.56, 0.21-1.45) and internal-cause (0.98, 0.65-1.48) mortality did not differ. In sibling comparisons (4765 siblings), excess all-cause and external-cause mortality were not observed (0.96, 0.67-1.36; and 1.14, 0.70-1.85), suicide risk was higher (2.57, 1.32-5.00), and accident mortality lower (0.19, 0.06-0.67). Relative hazards were greatest in those with a female legal sex and in adolescents. Adjustment for psychiatric clusters attenuated-but did not eliminate-the suicide mortality excess. INTERPRETATION: In Taiwan, transgender persons had higher all-cause and suicide mortality than population controls; in within-family comparisons, the suicide mortality excess persisted, indicating influences beyond shared familial factors. Prevention should prioritize targeted mental-health and safety interventions, with particular attention to adolescents and those with a female legal sex. FUNDING: Taiwan National Science and Technology Council.