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Cass Review on cross-sex hormones: much uncertainty, little long-term evidence

Cross-sex hormones — testosterone in young people born female, estrogen in young people born male — cause some lasting physical changes. The Cass Review had the University of York assess the studies on hormones in adolescents. Of 53 studies, one was of high quality, 33 of moderate and 19 of low quality (source). According to the researchers, no conclusions can be drawn on most outcomes.

What cross-sex hormones do — and what cannot be reversed

According to a review article in the Danish medical journal Ugeskrift for Læger, some changes are permanent, such as a deeper voice from testosterone and breast growth from estrogen. Both kinds of hormones reduce fertility; the extent of this and whether it is reversible is still unknown (source). In its advice of 30 June 2026, the Dutch Health Council also calls a testosterone-lowered voice and estrogen-induced breast growth irreversible (source).

What does the Cass Review say?

The York review of hormones in adolescents, summarised in the final report of the Cass Review (April 2024), concludes that high-quality research is lacking and that few studies follow participants for long. Specifically (source, paras 15.16 to 15.25):

• No conclusions can be drawn on the effect on gender dysphoria, body satisfaction, psychosocial health, cognitive development or fertility. No study assessed fertility in birth-registered females.
• There is moderate-quality evidence, mainly from before-and-after studies, that hormones may improve psychological health in the short term; the authors write that robust research with long-term follow-up is needed.
• Results on height/growth, bone health and cardiometabolic health are uncertain or inconsistent.
• On suicide, the report says it has been suggested that hormone treatment reduces the elevated risk of death by suicide, but that the evidence found did not support this conclusion (para 86 of the summary).
• The report advises NHS England to review its policy: hormones are an option from age 16, but the Review recommends "extreme caution" and a clear clinical rationale for not waiting until age 18 (recommendation 8).

Why the studies say little

According to the Cass Review, the studies had methodological problems: selective inclusion of patients, limited representativeness, often no comparison group, and where there was one, most studies did not control for key differences between groups (para 15.19). Many studies followed participants for less than a year (para 15.23). The original Dutch study by De Vries and colleagues from 2011 also contained 70 young people: part of a group of 111 referred young people, selected because they were the first ready for the next treatment step. The outcomes of the other 41 were not reported (para 2.10). See also the VUmc protocol and publication bias.

Internationally: more cautious policy in several countries

In the UK, the Tavistock clinic GIDS closed on 31 March 2024, a step NHS England links to the interim report of the Cass Review from 2022 (source). In Sweden, Socialstyrelsen judged in December 2022 that the risks of puberty blockers and gender-affirming treatment probably outweigh the expected benefits at group level; hormones can only be given in exceptional cases (source). The Norwegian commission Ukom recommended in March 2023 defining hormonal treatment of children and young people as "utprøvende behandling" (treatment in a research setting) (source). Denmark has a more cautious policy. In the Netherlands, the Health Council called the strength of evidence for the effects of hormone treatment low to very low on 30 June 2026, but saw no reason to organise care differently (source).

Detransition and regret

According to the Dutch Health Council, no definitive conclusions can be drawn about the number of cases of regret, because of mostly short follow-up and substantial dropout in studies (source). The Cass Review recommends that care be available for people who wish to detransition (recommendation 25). See detransition research and regret research.