medRxiv [Preprint]. 2025 May 16:2025.05.14.25327614. doi: 10.1101/2025.05.14.25327614.
ABSTRACT
BACKGROUND AND OBJECTIVES: Medical interventions for youth with gender dysphoria can include the use of gonadotropin releasing hormone analogs (GnRHas) for suppression of endogenous puberty. This analysis aimed to understand the impact of medical intervention initiated with GnRHas on psychological well-being among youth with gender dysphoria over 24 months.
METHODS: Participants were enrolled as part of the Trans Youth Care United States Study. Eligibility criteria for youth included a diagnosis of Gender Dysphoria and pubertal initiation. Youth with precocious puberty or pre-existing osteoporosis were ineligible. Youth reported on depressive symptoms, emotional health and suicidality at baseline, 6, 12, 18 and 24 months after initiation of GnRHas. Parent/caretaker completed the Child Behavior Checklist at baseline, 12 and 24 months after initiation of GnRHas. Latent Growth-Curve Models analyzed trajectories of change over the 24-month period.
RESULTS: Ninety-four youth aged 8-16 years (mean=11.2 y) were predominately Non-Hispanic White (56%), early pubertal (86%) and assigned male at birth (52%). Depression symptoms, emotional health and CBCL constructs did not change significantly over 24 months. At no time points were the means of depression, emotional health or CBCL constructs in a clinically concerning range.
CONCLUSION: Participants initiating medical interventions for gender dysphoria with GnRHas have self- and parent-reported psychological and emotional health comparable with the population of adolescents at large, which remains relatively stable over 24 months. Given that the mental health of youth with gender dysphoria who are older is often poor, it is likely that puberty blockers prevent the deterioration of mental health.What’s known on this subject: Puberty blockers are effective in halting endogenous puberty and prior research suggests improved mental health in youth with gender dysphoria. Few studies originate from the United States and most include older youth in later stages of puberty at initiation of blockers.What this study adds: This is the largest longitudinal cohort of youth with gender dysphoria initiating medical intervention beginning with puberty blockers in early puberty to be followed in the United States. Youth demonstrated both stability and improvement in emotional and mental health over 24 months.Contributors Statement Page: Dr. Olson-Kennedy conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and revised the manuscript.Dr. Durazo-Arvizu carried out follow-up analyses and critically reviewed the manuscript.Drs. Garofalo, Rosenthal, Chan, Chen, Ehrensaft, and Hidalgo conceptualized and designed the study, and critically reviewed and revised the manuscript.Drs. Wang and Wong carried out the initial analyses and critically reviewed and revised the manuscript.Dr. Radix critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
PMID:40463525 | PMC:PMC12132111 | DOI:10.1101/2025.05.14.25327614
