A large, peer-reviewed study published Friday in JAMA Network Open found that transgender youths prescribed puberty blockers had significantly lower adjusted odds of diagnosed mood disorders and suicidal thoughts and behaviors than transgender youths who did not receive the medications, adding new evidence to one of the most politically contentious areas of pediatric medicine.
The nationwide retrospective cohort study examined insurance claims data from more than 231,000 youths between 2016 and 2025, comparing transgender and cisgender youths who either did or did not receive puberty blockers.
While the study found that transgender youths overall experienced substantially higher rates of diagnosed mental health conditions than their cisgender peers, researchers concluded that puberty blocker treatment was associated with a measurable reduction in those disparities among transgender patients.
The authors wrote, “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.”
They added, “Prescription of a puberty blocker was associated with partial attenuation of this disparity, suggesting mental health benefits associated with this treatment for transgender youth.”
The study arrives as gender-affirming care continues to face political and legal challenges across the United States, where numerous states have enacted or considered restrictions on puberty blockers and hormone therapy for minors despite support from many major medical organizations.
Researchers from the Icahn School of Medicine at Mount Sinai, Yale School of Public Health, Harvard Medical School, the University of Michigan and other institutions analyzed data from the Mount Sinai Institute for Health Equity Research Multi-Payer Claims Database, which includes approximately 70 million commercial insurance enrollees, 60 million Medicaid beneficiaries and 16 million Medicare Advantage participants.
The study included 231,783 youths ages 10 to 17. Of those, 41,472 were identified as transgender through diagnostic coding, while 190,311 were categorized as cisgender. Researchers divided participants into four groups: transgender youths receiving puberty blockers, transgender youths not receiving puberty blockers, cisgender youths prescribed puberty blockers for precocious puberty and cisgender youths who did not receive the medications.
The researchers reported that only 1,260 transgender youths in the study received puberty blockers, underscoring how uncommon the treatment remains nationally. They estimated that transgender youths prescribed puberty blockers represented between one and four individuals per 100,000 patients during the study period.
According to the study, “Puberty blockers are an established, reversible intervention for central precocious puberty in children and gender dysphoria in adolescents.” The authors also noted that “Despite broad clinical support, these treatments are currently politically contested.”
Researchers found that being transgender was independently associated with substantially higher odds of diagnosed mood disorders and suicidal thoughts and behaviors compared with cisgender youths. After adjusting for demographic and socioeconomic variables, transgender youths had more than four times the odds of receiving a mood disorder diagnosis and more than 12 times the odds of receiving a diagnosis related to suicidal thoughts or behaviors.
The analysis also found that youths prescribed puberty blockers as a whole appeared to have higher rates of mental health diagnoses than youths who were not prescribed the medications. However, the authors emphasized that this finding reflects the fact that puberty blockers are prescribed to populations already experiencing significant medical or psychological conditions, including transgender youths with gender dysphoria and cisgender youths with precocious puberty.
Within the transgender population, the pattern differed substantially.
The study found that transgender youths prescribed puberty blockers had approximately half the adjusted odds of diagnosed mood disorders compared with transgender youths who did not receive the medications. They also had roughly one-fifth the adjusted odds of diagnosed suicidal thoughts and behaviors.
The authors wrote, “Importantly, puberty blocker prescription was associated with lower odds of mood disorder and suicidality diagnoses, but only among transgender youths.”
They cautioned against interpreting the findings as proof of causation.
“Additionally, claims data are merely observational and do not allow for determining definitive causes and can show only associations,” the researchers wrote.
The paper repeatedly emphasizes that its findings demonstrate statistical associations rather than direct causal effects.
Researchers also acknowledged that insurance claims cannot account for important influences on mental health, including family acceptance, school environment, community support or counseling services.
They wrote, “Due to limitations of the administrative claims database being analyzed, we could not adjust for factors like psychosocial support.”
Even so, the authors concluded that their findings were generally consistent with previous research examining transgender adolescents receiving gender-affirming care.
The study states, “Results of this cohort study broadly align with those of other studies to date, showcasing a generally higher mental health burden among transgender youths in comparison with cisgender youths.”
Researchers also reported that transgender youths receiving puberty blockers did not experience mental health outcomes identical to cisgender youths, suggesting that puberty suppression alone may not eliminate broader social and psychological stressors affecting transgender adolescents.
The discussion notes that persistent differences may reflect bullying, discrimination, family rejection and other minority stressors documented in previous research.
The authors wrote, “This pattern may indicate that while puberty blockers may be associated with mitigation of some distress associated with undesired pubertal changes, their use in isolation may not fully address complex psychosocial stressors at play.”
They suggested that future research should examine whether earlier access to gender-affirming hormone therapy following puberty suppression may further improve outcomes but stressed that additional prospective research is needed before drawing conclusions.
The paper also acknowledged several limitations.
Because the research relied on insurance billing records, investigators could identify diagnoses and prescriptions but could not determine why physicians made individual treatment decisions or measure the quality of family or community support available to patients.
Researchers further noted that the insurance database does not represent every American youth and may not perfectly reflect national demographics. They also acknowledged that their statistical model may not have captured every potential confounding factor influencing mental health outcomes.
Nevertheless, the authors concluded that the findings contribute important evidence to an evolving scientific literature that continues to be scrutinized amid ongoing political debate.
The study concludes, “Ultimately, this analysis advances our understanding of the association between puberty blocker use and mental health diagnoses, provides further evidence countering misinformation implying negative mental health associations for transgender youths receiving this class of medications, and highlights needed future research into the mechanisms by which puberty blocker use may be associated with reduced but not fully eliminated mental health inequities for this population.”
The research was funded by the National Institutes of Health’s National Cancer Institute. According to the authors, “The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.”
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This is very useful evidence and bolsters the professional society guidelines.
“The current Endocrine Society/AACE guidelines recommend hormone therapy for:
Transgender and gender diverse adults with persistent gender identity (typically of which they’ve been aware for at least 6 months) that does not align with sex recorded at birth who seek treatment, who have capacity to make medical decisions, and in whom potential confounding mental health conditions are addressed.
Transgender and gender diverse adolescents with persistent gender identity (typically of which they’ve been aware for at least 6 months) that does not align with sex recorded at birth who seek treatment, who have capacity to make medical decisions, in whom potential confounding mental health conditions are addressed, and who have been evaluated by trained mental health professionals who have expertise in gender incongruence in children/adolescents. Decisions regarding both puberty blockade and hormone therapy in adolescents should made with the input of the qualified mental health professional, the endocrinologist or clinician with experience in hormone therapy/puberty blockade in children, the child, and the family.”
https://pro.aace.com/recent-news-and-updates/aace-position-statement-transgender-and-gender-diverse-patients