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NIH-Funded Blocker Study Finds No Mental Health Improvement Over 2 Years; No Control Group, 37% Missing at 24 Months

Mental and Emotional Health of Youth after 24 months of Gender-Affirming Medical Care Initiated with Pubertal Suppression

Cohort & registry studiesPuberty blockersMental health & suicide
Authors
Johanna Olson-Kennedy, Ramon Durazo-Arvizu, Liyuan Wang, Carolyn F. Wong, Diane Chen, Diane Ehrensaft, Marco A. Hidalgo, Yee-Ming Chan, Robert Garofalo, Asa E. Radix, Stephen M. Rosenthal
Journal
medRxiv (preprint)
Year
2025
Source
https://doi.org/10.1101/2025.05.14.25327614

Summary

This NIH-funded study followed 94 children and young teens (average age 11) who started puberty blockers at four large US gender clinics. Over two years, their own reports of depression and emotional wellbeing, and parents' reports of behaviour, did not measurably improve. Average scores were normal from the start. The authors read this as a sign blockers probably prevented a decline, but with no comparison group that claim is untested. More than a third of depression data were missing at two years, about a third started cross-sex hormones during the study, and the results reported differ from those first planned. In 2024 the lead author told The New York Times she had delayed publishing for fear the results would be "weaponized"; they appeared as an unreviewed preprint (early version) in May 2025. It shows no measurable mental health benefit.

Key findings

  • 94 youth aged 8 to 16 (average 11; 52% born male; most in early puberty) starting puberty blockers at four US clinics were followed for 2 years.
  • Their own reports of depression and emotional health, and parents' reports of problems, showed no measurable change over 2 years; only rule-breaking behaviour fell slightly.
  • 18% had moderate or severe depression at the start (16 of 88) and 23% at 2 years (13 of 59).
  • Only 59 of 94 had depression data at 2 years, so 37% were missing.
  • 11 started estrogen or testosterone within the first year and 20 more in the second, so a third took cross-sex hormones during the study.
  • 11 youth reported suicidal thoughts in the 6 months before the start and 5 at 2 years; there were no suicide deaths.
  • The authors concluded blockers "likely" prevent mental health from getting worse, although with no comparison group the study could not test this.
  • The NIH progress report expected falls in depression, anxiety, trauma symptoms, self-harm and suicidal thoughts, and better body image and quality of life; these improvements were not shown.

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.

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. (Full-text conclusion: the average mental health as reported by both the youth and parents remains in a clinically non-significant range over two years.)