Weakness of the evidence base
Three independent evaluations (the Cass Review, NICE and SBU) judged the evidence for puberty blockers and cross-sex hormones in minors with gender dysphoria to be weak, of very low certainty or insufficient.
Cass Review (UK, 2024)
After four years of work for NHS England, Hilary Cass describes gender care for young people as "an area of remarkably weak evidence" (final report, April 2024). In March 2024, before the final report, NHS England decided that puberty blockers are no longer available as a routine commissioning treatment option for under-18s; the Cass Review advises that they only be prescribed in the context of a clinical trial. See the final report and the UK government summary.
NICE (UK, 2020)
The evidence review NICE prepared in October 2020 on puberty blockers (GnRH analogues) for gender dysphoria concludes that the studies are small, uncontrolled observational studies and that all results are of "very low certainty" using modified GRADE. See the NICE evidence review (October 2020).
SBU (Sweden, 2022)
The Swedish SBU report 342 (February 2022) is a systematic review of hormone treatment of children and adolescents with gender dysphoria: it found 24 relevant studies, no randomised trials, and concluded that the evidence is insufficient to assess the effects on psychosocial and mental health, cognition, body composition and metabolic markers. In December 2022 the Swedish National Board of Health and Welfare (Socialstyrelsen) recommended that these treatments be provided in the context of research and otherwise only in exceptional cases. See SBU, the published review and Socialstyrelsen.
What this means
Three independent evaluations, each concluding that the evidence is weak, of very low certainty or insufficient. The Dutch Protocol — developed in the Netherlands and subsequently adopted in the UK and internationally, according to the Cass Review — rests on an evidence base that these evaluations judge to be weak. In the Netherlands the Health Council advised on 30 June 2026, at the request of the Minister of Health, on transgender care for young people: it described the certainty of the evidence as low to very low and found effects on cognition, fertility and the long term insufficiently studied, but saw no reason to organise the care differently and advised strengthening the due-care requirements in the revision of the Quality Standard. See the Health Council advice and the Cass Review.