A UK clinical trial assessing the risks and benefits of puberty blockers for children questioning their gender has been paused following new concerns raised by the Medicines and Healthcare products Regulatory Agency (MHRA), the Department of Health and Social Care (DHSC) announced Friday evening.
The pause affects the Pathways trial, which had been slated to begin recruiting participants but will now remain on hold until the MHRA and King’s College London, the trial sponsor, resolve issues related to participant safety. The MHRA has specifically suggested raising the minimum age for participation from 10 to 14, citing “potentially significant and, as yet, unquantified risk of long-term biological harms.”
The trial’s postponement comes after a recommendation from the 2024 Cass review into children’s gender care, which found the evidence base supporting the benefits of puberty blockers for young people with gender dysphoria to be “weak.” Dr. Hilary Cass, who led the review, previously stated that while the evidence was limited, a trial was necessary to better understand the effects of the medication, given the strong beliefs held by clinicians, families and the young people themselves.
A DHSC spokesperson emphasized that the safety and wellbeing of children and young people remain the primary consideration. “The MHRA has now raised new concerns – directly related to the wellbeing of children and young people – and scientific dialogue will now follow with the trial sponsor,” the spokesperson said. “This trial will only be allowed to go ahead if the expert scientific and clinical evidence and advice conclude This proves both safe and necessary.”
The Pathways trial was designed to involve over 220 children aged between approximately 11 and 15, examining the impact of puberty blockers on their physical, social, and emotional wellbeing. Initial plans indicated the youngest participants could be as young as 10 or 11 for biological females and 11 or 12 for biological males. However, the MHRA’s concerns center on the potential for “long-term biological harms” in younger participants, advocating for a “graded/stepwise approach” beginning with those aged 14 and above.
King’s College London affirmed its commitment to the wellbeing of young people and its intention to collaborate with the MHRA to address the regulator’s concerns. “The wellbeing and health of young people with gender incongruence and their families has been, and will remain, our priority,” a spokesperson stated. “We will continue to work with the MHRA to support their further review of the trial, which has been designed by world-leading academics with scientific rigour at its core.”
The pause in the Pathways trial follows a decision by NHS England to largely discontinue the routine prescription of puberty blockers, confining their use to research settings. The MHRA’s letter outlining its concerns likewise called for more detailed monitoring of bone density and a more rigorous consent process for any future participants.
Professor Sir Jonathan Montgomery, of University College London, noted that the MHRA’s actions indicate an effort to strengthen the trial protocol, not halt it entirely. “The letter also states that these are scientific issues and not a result of legal action,” he said. “The focus here is on safety, as it should be. This pause shows the regulatory process working properly and in the interests of participants.”
Discussions between the MHRA and King’s College London are scheduled to begin next week, with the future of the Pathways trial contingent on the outcome of those deliberations.
