In a significant development for youth gender care, UK regulators have given the green light to the first clinical trials of puberty-blocking drugs in children since their routine use in NHS gender clinics was prohibited.
Addressing a Critical Evidence Gap
The approval follows the landmark Cass Review, a major NHS England investigation led by Dr Hilary Cass from 2020 to 2024. The review concluded that evidence supporting hormone treatments for children seeking gender transition was "built on shaky foundations".
These new trials, spearheaded by King's College London (KCL), are specifically designed to investigate both the potential benefits and risks of administering these drugs to children referred to gender services.
Dr Michael Absoud, deputy chief investigator for the study at KCL, stated: "Young people with gender incongruence and their families have told us that they do not have the information that they need to make informed choices about their care." He added that the new studies will provide more specific information about puberty suppression and closely monitor impacts on development.
The Pathways Trial: Scope and Design
The central study, named the Pathways trial, plans to recruit approximately 250 children under the age of 16 who have been referred to NHS gender services in England and Wales. Discussions are also underway to include participants from Scotland and Northern Ireland.
Eligibility criteria are strict: participants must have experienced at least two years of "gender incongruence", must have started puberty, and must be capable of giving informed consent. Consent from at least one parent or guardian is also mandatory.
The trial will directly compare two groups over a two-year period: one receiving puberty-suppressing drugs alongside non-medical care, and another receiving non-medical care alone.
Researchers confirmed that, despite the current ban, some children in the trial may be permitted to continue treatment if it is deemed "clinically appropriate" after the study concludes.
Controversy and Broader Context
The use of puberty-blockers became a subject of intense medical and public debate, particularly as referrals to NHS gender clinics saw a dramatic rise—from just 210 per year in 2011 to over 5,000 annually by 2022, according to the Cass Review.
Doctors' groups have voiced serious concerns about potential harms, which could include bone density loss, future fertility problems, and disruption to crucial brain development during puberty. Some medical professionals even argued that conducting such a clinical trial would be unethical given these potential risks.
Conversely, transgender advocacy groups have contended that the Cass Review and parts of the medical establishment have downplayed the benefits of gender-affirming care.
A second, linked trial called Pathways Connect will focus specifically on brain health. Researchers will perform brain scans on a subset of participants and assess their cognitive function and overall neurological well-being.
Professor Emily Simonoff, chief investigator at KCL, emphasised the need for robust evidence: "Clinical care should always be underpinned by robust evidence... this research is focused solely on informing and improving healthcare by better understanding how to support the physical and mental health of young people with gender incongruence."
Dr Ronny Cheung, a consultant paediatrician at KCL not involved in the trial, noted that while the entry criteria are strict, they reflect standard practice for paediatric trials, especially where the risks and benefits of a treatment are not yet fully quantified.
The research team anticipates that results from these pivotal trials will be available in approximately four years.
