The planned UK clinical trial, known as the Pathways trial, investigating the effects of puberty-blocking medication on children and adolescents, has been temporarily paused following an intervention by the Medicines and Healthcare products Regulatory Agency (MHRA). This action has delayed the recruitment of participants and reignited debate concerning the safety, ethics, and research design within gender medicine.
The MHRA's intervention stems from concerns about long-term biological risks and a recommendation to raise the minimum age eligibility for participants.
Regulator's Safety Intervention
On 20 February 2026, the Department of Health and Social Care confirmed that the MHRA had raised "new concerns directly related to the wellbeing of children and young people" in the study, leading to a temporary halt in preparations and recruitment. Scientific discussions are now underway between the regulator and the trial sponsor, King’s College London, to implement substantial amendments to the study protocol before it can proceed.
A central point of the MHRA's intervention is the recommendation to raise the minimum age of participation to 14, a significant increase from the previously proposed lower limit of approximately 10–11 years. The regulator cited an "unquantified risk of long-term biological harms" and advocated for a cautious, stepwise approach before enrolling children under 14. The Department of Health emphasised that the trial’s progress hinges on expert scientific and clinical evidence concluding that it is both safe and necessary, underscoring that the safety and wellbeing of participants remain paramount.
Pathways Trial Context and Design
The Pathways trial was initiated in response to the 2024 Cass Review into children’s gender services, which highlighted the weak evidence base for puberty-blocking drugs and called for more rigorous research. The study was designed to examine the safety and broader impacts of gonadotropin-releasing hormone (GnRH) agonist treatment in young people questioning their gender.
Researchers had aimed to recruit around 226 young people, potentially aged 10 to 15, to compare outcomes between those starting the puberty-suppressing medication immediately and those who delayed treatment. Key assessment areas were planned to include physical development, bone health, quality of life, and psychological wellbeing over an extended follow-up period.
This trial emerged following policy shifts by NHS England, which ceased routine prescribing of puberty blockers for under-18s outside research settings due to safety and clinical effectiveness concerns. Clinical trials involving children are subject to particularly stringent oversight under MHRA regulation, which includes continuous safety appraisal and the ability to mandate amendments if participant protection is judged inadequate.
Scientific and Public Controversy
The MHRA's action has sparked debate among experts. Supporters argue it exemplifies the scientific process at work, ensuring robust safeguards for studies involving children and potentially life-altering treatments. Conversely, critics suggest the regulator is bowing to political pressure, not new evidence. Dr Hilary Cass, who led the influential review, called the regulator's claims "completely bizarre" and questioned the abrupt age change's scientific justification, warning it could compromise the study's validity.
The trial is also a subject of public controversy, with campaigners arguing against exposing children to experimental hormone treatments, while some trans rights advocates view the measures as overly restrictive.
Broader Policy Landscape
The pause is set against the backdrop of evolving UK policy. In March 2024, NHS England formally ended routine prescriptions of puberty blockers for minors in gender clinics. Further restrictions in December 2024 effectively banned the sale and prescription of these medications for gender dysphoria in under-18s outside of approved clinical research, aiming to confine their use to controlled scientific settings.
Public opinion polls from late 2025 indicated significant public scepticism towards these trials, with many adults favouring mental health and psychological support over medical interventions for under-16s.
Focus on Long-Term Safety
The MHRA's communication with the trial sponsor specifically highlighted poorly understood long-term biological risks, including potential effects on fertility, bone density, and irreversible developmental change. Ethical concerns were also raised regarding the capacity of young adolescents to understand and report certain physiological signals. Regulators have also requested clear post-trial care pathways to ensure participants retain safe and appropriate ongoing healthcare upon concluding or leaving the study.
Next Steps
No young people are currently being enrolled in the Pathways study. Scientific discussions between regulatory authorities and trial sponsors will now focus on detailing revised eligibility criteria, enhanced monitoring safeguards, and improved ethical frameworks. If the trial eventually proceeds, it could yield much-needed data on the effects of puberty-blocking medicines in adolescents with gender dysphoria. However, the current pause vividly highlights the intrinsic tensions between medicine, ethics, science, and public concern in this contentious area of clinical research.
