Mental Health of Youths Who Use Puberty Blockers

Importance: Puberty blockers are an established, reversible intervention for central precocious puberty in children and gender dysphoria in adolescents. Despite broad clinical support, these treatments are currently politically contested. Objective: To characterize the mental health of transgender youths prescribed puberty blockers compared with cisgender peers who received these medications for treatment of precocious puberty and with transgender and cisgender youths who did not receive these medications. Design, Setting, and Participants: This retrospective cohort study used data from a US nationwide, multipayer claims database from January 2016 to January 2025. Youths aged 10 to 17 years were categorized into 4 cohorts based on gender modality (transgender or cisgender) and prescription of a puberty blocker (yes or no). Main Outcomes and Measures: Primary outcomes were International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnoses of mood disorders and suicidal thoughts and behaviors. Inverse probability-weighted generalized estimating equation models were fit to obtain adjusted odds ratios (aORs) and 95% CIs, adjusting for demographics, payer type, region, year, socioeconomic disadvantage, and policy environment indices. In demographics, female gender marker is used to indicate that an F (female) has been applied as a marker for the individual by some entity (eg, a medical professional or government body). Results: Among 231 783 youths in the analytical sample, 41 472 youths (17.89%) were transgender (median [IQR] age at baseline, 9.00 [7.00-11.00] years; 31 246 with female gender marker [75.34%]) and 190 311 youths (82.11%) were cisgender (median [IQR] age at baseline, 8.00 [6.00-10.00] years; 128 942 with female gender marker [67.75%]). Being transgender was associated with higher odds of mood disorder diagnosis (aOR, 4.42 [95% CI, 4.24-4.60]) and suicidal thoughts and behaviors (aOR, 12.21 [95% CI, 10.69-13.95]) compared with being cisgender. Being prescribed a puberty blocker was associated with higher odds of mood disorder diagnosis (aOR, 2.11 [95% CI, 2.02-2.19]) and suicidal thoughts and behaviors (aOR, 3.04 [95% CI, 2.65-3.49]) compared with no prescription. However, among transgender youths, prescription of a puberty blocker was associated with decreased adjusted odds of mood disorder diagnosis (aOR, 0.52 [95% CI, 0.45-0.60]) and suicidal thoughts and behaviors (aOR, 0.20 [95% CI, 0.14-0.29]). Conclusions and Relevance: In this study, transgender youths overall had substantially higher rates of diagnosed mood disorder and suicidal thoughts and behaviors than their cisgender peers, highlighting the need for population-specific interventions. Prescription of a puberty blocker was associated with partial attenuation of this disparity, suggesting mental health benefits associated with this treatment for transgender youth.