Mood disorders and suicidal thoughts are more common among transgender youths compared with their cisgender peers, a study has found. Prescription of a puberty blocker may help lessen such disparity, indicating mental health benefits for transgenders.
“Puberty blockers are an established, reversible intervention for central precocious puberty in children and gender dysphoria in adolescents,” the researchers said. “Despite broad clinical support, these treatments are currently politically contested.”
A total of 231,783 youths were included in this retrospective cohort study, which used data from a US nationwide, multipayer claims database form January 2016 to January 2025. The research team categorized youths aged 10‒17 years into four cohorts based on gender modality (transgender or cisgender) and prescription of a puberty blocker (yes or no).
Of the participants, 41,472 (17.89 percent) were transgender (median age at baseline 9 years; 31,246 [75.34 percent] with female gender marker) and 190,311 (82.11 percent) were cisgender youths (median age at baseline 8 years; 128,942 [67.75 percent] with female gender marker). [JAMA Netw Open 2026;9:e2623302]
Compared with being cisgender, being transgender significantly correlated with a greater likelihood of having a mood disorder diagnosis (adjusted odds ratio [aOR], 4.42, 95 percent confidence interval [CI], 4.24‒4.60) and suicidal thoughts and behaviours (aOR, 12.21, 95 percent CI, 10.69‒3.95).
Puberty blockers
Prescription of a puberty blocker, compared with no prescription, also resulted in a higher likelihood of mood disorder diagnosis (aOR, 2.11, 95 percent CI, 2.02‒2.19) and suicidal thoughts and behaviours (aOR, 3.04, 95 percent CI, 2.65‒3.49). However, use of a puberty blocker among transgender youths significantly reduced the odds of having mood disorders (aOR, 0.52, 95 percent CI, 0.45‒0.60) and suicidal thoughts and behaviours (aOR, 0.20, 95 percent CI, 0.14‒0.29).
“Notably, this attenuation did not return odds to baseline but instead reduced them, resulting in a slightly higher odds of a mood disorder diagnosis and a markedly reduced odds for suicidality compared with transgender youths not using puberty blockers,” the researchers said.
“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 added.
The remaining elevated adjusted odds could be potentially explained by a form of “developmental asynchrony” among transgender youths awaiting gender-affirming hormone therapy and cisgender youths experiencing early puberty relative to their peers, according to the researchers.
Existing psychological and social burdens among youths experiencing central advanced puberty may impair coping mechanisms for dealing with early puberty, which could worsen negative mental health outcomes. [JAMA Netw Open 2025;8:e2516679]
Similarly, those experiencing delayed puberty appear to have higher rates of low self-esteem, depression, peer stress, social isolation, and bullying. [Curr Opin Endocr Metab Res 2020;14:15-21]
“Taken together, these findings suggest that it is possible that earlier initiation of gender-affirming hormone therapy for transgender youths, so that they may experience puberty in synchronicity with their peers, may be associated with reduction or elimination of observed disparities compared with cisgender youths not using puberty blockers,” the researchers said.
“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,” they noted.