The United Kingdom’s National Health Service (NHS) has announced the launch of a landmark clinical trial to assess the safety and effectiveness of puberty blockers for young people experiencing gender incongruence, marking a pivotal moment in the global debate over gender-affirming care for minors. The PATHWAYS TRIAL, set to begin recruiting imminently, will involve 226 participants under the age of 16, all of whom must have experienced gender incongruence for at least two years and possess stable enough mental health to assent to the study, with parental or guardian consent required.
This randomized trial will split participants into two groups: one will receive puberty blockers immediately, while the other will begin treatment after a one-year delay. Over a two-year period following randomization, researchers will closely monitor the children’s quality of life and emotional well-being, aiming to provide much-needed data on a treatment that has sparked intense controversy and policy shifts across the UK and beyond. As reported by the BBC, this is the world’s first randomized clinical trial of puberty blockers for gender incongruence among youth—a milestone that comes more than 25 years after Dutch clinicians first pioneered the practice and nearly 15 years after the NHS began offering such treatments without formally studying their long-term impacts.
The trial’s launch follows a period of significant upheaval in the UK’s approach to pediatric gender medicine. In 2024, the NHS-commissioned Cass Review, led by pediatrician Dr. Hilary Cass, concluded that the evidence base supporting puberty blockers for gender dysphoria or incongruence was “remarkably weak.” As a result, the NHS banned all physicians, including those in private practice, from prescribing puberty blockers for gender-related distress outside of a clinical trial. The Labour government, which came to power in July 2024, later extended this ban indefinitely, a move that was met with both relief and outrage from different corners of British society.
In the wake of the Cass Review, the NHS shuttered its Gender Identity Development Service (GIDS), the country’s only pediatric gender clinic, and began establishing new gender-clinic hubs to provide psychotherapy and psychosocial support instead of medical interventions. According to reporting by Hazard Ratio, this shift has left many families distressed and frustrated, particularly those who believe that gender-transition drugs are essential for their children’s well-being. The NHS, for its part, has consistently promised that a clinical trial would be forthcoming—a recommendation echoed in the Cass Review—and now, after years of delays, the PATHWAYS TRIAL is poised to begin.
But the PATHWAYS TRIAL is just one part of a broader research initiative. The NHS is also launching PATHWAYS CONNECT, a study focused on puberty blockers’ impacts on brain development. This study will enroll about 150 participants from the clinical trial and another 100 from the PATHWAYS HORIZON observational study, which follows 3,000 gender-incongruent youth receiving psychosocial care instead of medical intervention. As noted in a paper published last year and cited by Hazard Ratio, understanding the neurocognitive effects of puberty blockers is an “urgent research priority,” with critical questions remaining about potential arrested development of cognitive function.
Additionally, the PATHWAYS VOICES study will gather qualitative data by interviewing youth about their experiences with gender incongruence and the new NHS care model. All of these studies have received the necessary regulatory and ethics approvals, a point emphasized by NHS officials in response to criticism from campaigners and some clinicians who question the ethics of enrolling children in such trials.
Participants in the clinical trial will undergo comprehensive physical and medical examinations before and during the study, and will receive ongoing psychosocial support regardless of whether they are in the immediate or delayed treatment group. After the two-year trial period, each young person’s future treatment options—continuing puberty suppression, stopping treatment, or starting gender-affirming hormones—will be discussed with their doctor and reviewed by a National Multidisciplinary Team, according to NHS materials.
As Professor Emily Simonoff, chief investigator of the study and professor of child and adolescent psychiatry at King’s College London, explained in a statement to 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 added that the study is not seeking a “one size fits all finding,” but rather aims to provide nuanced, individualized insights. Dr. Michael Absoud, deputy chief investigator, echoed this sentiment: “All parts of the PATHWAYS study are important to give vital evidence about the best way to support young people with gender incongruence. The new studies launched today will give us more information specifically about puberty suppression and will closely monitor any impact on young people’s development.”
The trial has not been without its detractors. Some campaigners, including Keira Bell—who famously took the Tavistock gender clinic to court in 2020 after being prescribed puberty blockers as a teenager—have threatened legal action, arguing that it is “disgusting” to enroll children in a trial for drugs already banned outside research settings. The British Medical Association has also criticized the Cass Review as “deeply flawed,” claiming it relied on a “selective and inconsistent use of evidence.” Meanwhile, LGBTQ+ organizations such as Stonewall maintain that all young people deserve access to the best possible medical care, guided by robust evidence and with their voices at the center of decision-making.
The UK’s new research program has reverberated internationally. On November 19, 2025, New Zealand’s Health Minister Simeon Brown announced that, effective December 19, new prescriptions of puberty blockers for transgender young people would be banned while the country awaits results from the UK trial, which are expected in 2031. Brown emphasized that the decision was not political but based on clinical evidence, referencing both the Cass Review and a November 2024 review by New Zealand’s own Ministry of Health. “When it comes to children’s health, clinical evidence must guide decisions to ensure any medicine given to young Kiwis is proven, safe and effective,” Brown wrote. However, those already receiving puberty blockers for gender dysphoria in New Zealand will be allowed to continue, and the drugs remain available for other conditions such as early-onset puberty, endometriosis, and prostate cancer.
New Zealand’s move mirrors the UK’s cautious approach, with Brown stating, “Cabinet has put in place stronger safeguards so families can have confidence that any treatment is clinically sound and in the best interests of the child.” Like in the UK, the ban and the reviews underpinning it have drawn criticism from medical groups, LGBTQ+ advocates, and academics, who argue that the evidence base is being misrepresented and that vulnerable youth may be left without needed care.
As the first participants prepare to enroll in the PATHWAYS TRIAL, the world will be watching closely. The trial’s results—expected to begin emerging in four years and to inform policy as far afield as New Zealand—may finally provide the rigorous data that has long been missing from one of the most contentious debates in modern medicine. For now, the future of puberty blockers in gender care remains uncertain, but the search for answers is finally underway.
