Regulators in the United Kingdom have approved the first clinical trials of puberty-blocking drugs for children since a sweeping ban was enacted last year, reigniting a fierce national debate over the ethics, safety, and scientific basis of gender-affirming care for minors. The new NHS-backed Pathways Trial, set to begin recruiting in early 2026, will enroll more than 200 children aged 10 to 15 who have been diagnosed with gender incongruence for at least two years and are already under NHS gender services. The project marks a significant shift in approach after the 2024 ban on the routine use of such medications outside research settings.
The decision to greenlight the trial follows the influential Cass Review, led by Dr Hilary Cass, which concluded that the evidence supporting hormone treatments for children seeking gender transition was “built on shaky foundations.” According to Dr Cass, “My review uncovered a very weak evidence base for benefits from the use of puberty blockers for children and young people with gender dysphoria. In fact, some children had more negative than positive effects. However, given that there are clinicians, children and families who believe passionately in the beneficial effects, a trial was the only way forward to make sense of this.”
The Pathways Trial, spearheaded by researchers from King’s College London and the South London and Maudsley NHS Foundation Trust, is designed to fill those evidence gaps. Professor Emily Simonoff, the study’s chief investigator and professor of child and adolescent psychiatry at King’s College London, told BBC Radio 4, “We are looking very much at the balance between, possibly, benefits for mental health and quality of life, and any possible risks or harms.” She emphasized that the study is not seeking a “one size fits all finding,” but rather aims to provide clarity for families and clinicians grappling with what remains a highly contested and emotionally charged field of medicine.
Under the trial protocol, participants will undergo intensive medical and psychological screening. Both the young person and their parent or legal guardian must provide informed consent. The children, who must have entered puberty but be younger than 16, will be randomly assigned to one of two groups: one starting puberty blockers immediately and the other after a one-year delay. Both groups will be closely monitored over a two-year period, with researchers examining impacts on bone density, brain development, fertility, mental health, and overall wellbeing. Recruitment is expected to begin in January 2026, with five to six children joining the study each month, and the first results anticipated in about four years.
The youngest participants are expected to be girls aged 10 to 11 and boys aged 11 to 12, with the maximum age for enrollment set at just under 16. More than half of the children will receive hormone-suppressing drug injections to temporarily halt physical changes associated with puberty, such as the growth of facial hair, onset of periods, and development of breasts. At the end of the trial, each participant’s ongoing care needs will be assessed individually, and some may continue on puberty blockers if deemed clinically appropriate.
Notably, the trial will not be available in Scotland, as confirmed by King’s College London researchers. The broader Pathways research programme also includes brain imaging studies—known as Pathways Connect—to determine whether suppressing puberty affects adolescent brain development and cognition. Professor Simonoff explained, “We know that adolescence is a time of rapid brain development and rapid accrual of new thinking abilities, and people have raised the theoretical risk that interfering with puberty during this important time might impact brain development and cognition. There have been remarkably few studies in this area.”
The trial’s announcement has drawn sharp criticism from some clinicians, campaigners, and political figures. Former UK Prime Minister Liz Truss condemned the NHS’s decision in forceful terms, labeling the move “evil” and accusing the health service of reviving what she called “dangerous transgender ideology.” Truss argued that the study represents “state-sanctioned harm” and risks repeating the mistakes that led to the collapse of the Tavistock Gender Identity Development Service, which faced allegations of rushed treatment and inadequate safeguarding. In her words, “Allowing 10-year-olds to take puberty blockers is indefensible.” She maintained that puberty is a natural developmental process that should not be interrupted, especially by drugs with unresolved questions over their impact on bone health, fertility, and brain development. “The state has a duty to protect minors from what she considers unproven and potentially harmful treatments, and she believes the new trial risks repeating a system that prioritised ideology over child welfare,” according to her statements.
Other critics have threatened legal action. Keira Bell, who took the Tavistock clinic to court in 2020 after being prescribed puberty blockers as a teenager, said the trial should be halted immediately. She described it as “disgusting” that children are being put on drugs already banned for being “unsafe.” Bell’s earlier case saw the High Court rule that under-16s were unlikely to be able to give informed consent to puberty blockers, though this was later overturned by the Court of Appeal, which held that doctors could judge whether young people can consent to such treatment.
The NHS, however, insists that a controlled and closely monitored trial is the only way to resolve the persistent uncertainty. A spokesperson for the Department of Health and Social Care said, “Young people with gender incongruence need access to high-quality, safe and effective care. We are following the Cass Review, which was clear that the evidence on care for these children is lacking, and proposed this research to help provide it. Medical care must always be based on solid evidence, and children’s safety must come first.”
Advocacy groups such as Stonewall have expressed support for the trial, provided it is guided by evidence and prioritizes the voices and wellbeing of trans young people and their families. “We urge the government and policymakers to invest in delivering excellent healthcare for trans young people and to make sure the voices of trans young people and their families are at its core,” a Stonewall spokesperson said.
The Pathways Trial and its associated research projects represent a pivotal moment in the UK’s approach to gender care for children. The studies are expected to clarify whether puberty blockers, which were originally developed to treat precocious puberty in the 1980s and are administered via injections such as triptorelin, have significant effects—positive or negative—on adolescent development when used for gender incongruence. The NHS and its research partners hope the findings will finally provide the robust evidence base that has long been missing from this contentious area of medicine.
As the first children prepare to enroll in the Pathways Trial in the coming months, the eyes of the medical, political, and advocacy communities will be firmly fixed on the UK. The outcome of this research could shape not only national policy but also inform global debates about the ethics and practicality of medical interventions for gender-questioning youth.
With passions running high on all sides, the Pathways Trial is set to become one of the most closely watched and consequential medical studies of the decade—one that may finally offer answers to questions that have divided families, clinicians, and policymakers for years.
