The most up-to-date reviews of puberty blockers and cross-sex hormones for minors identify “significant conceptual and methodological flaws” in the evidence base.

Zepf et al.’s systematic review Beyond NICE (2024) found that the available evidence on puberty blockers and cross-sex hormones for minors with gender dysphoria remains limited. Existing studies are characterized by small sample sizes, weak methodology, missing data, high dropout rates, lack of appropriate controls, and limited long-term follow-up. The review also identified significant conceptual and methodological flaws across the literature, limiting confidence in reported findings and making reliable conclusions difficult.

Some studies report short-term reductions in gender dysphoria, depression, or suicidality following cross-sex hormones, but findings remain inconsistent and methodologically weak. Long term results remain unknown. In some cases, studies include no meaningful statistical analysis or suffer from substantial loss to follow-up, further limiting interpretation of outcomes and risks.

^{Zepf, F.D. et al. (2024). Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie. Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 1-21. DOI: 10.1024/1422-4917/a000972
PDF: Full paper PDF}

^{National Institute for Health and Care Excellence (NICE). (2020). Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria. NHS England and NHS Improvement.}

^{PDF: NICE Evidence Review PDF}

^{National Institute for Health and Care Excellence (NICE). (2020). Evidence review: Gender-affirming hormones for children and adolescents with gender dysphoria. NHS England and NHS Improvement.}

^{PDF: NICE Evidence Review – Gender-affirming hormones for children and adolescents with gender dysphoria}