UK Puberty Blocker Trial Paused After Medicines Regulator Raises Safety Concerns
The Pathways clinical trial investigating the use of puberty blockers for children has been paused following intervention from the Medicines and Healthcare products Regulatory Agency (MHRA). The regulator has expressed significant concerns about the wellbeing of young participants, specifically recommending that the minimum age limit be raised from 10 to 14 years old.
Regulator Warns of "Unquantified Risk" of Long-Term Harms
In a letter to trial organizers, the MHRA highlighted what it described as "potentially significant and, as yet, unquantified risk of long-term biological harms" to participants. The agency emphasized that biological safety has not been definitively demonstrated in this proposed cohort of young people.
The regulator stated: "Since potentially significant and, as yet, unquantified risk of long-term biological harms is present to participants and biological safety has not been definitively demonstrated in this proposed cohort, at the very least, there should be a graded/stepwise approach starting with those aged 14 as the lower limit of eligibility."
Trial Design and Recruitment Plans
The Pathways trial was designed to recruit approximately 226 young people over three years. Originally, the youngest participants were expected to be:
- 10 to 11 years old for biological females
- 11 to 12 years old for biological males
However, trial organizers had noted that rigorous selection processes would likely mean participants would be older than these minimum ages. The trial was announced following recommendations from the Cass review into children's gender care, which found the existing research on puberty blockers to be of poor quality.
Government and Institutional Responses
The Department of Health and Social Care confirmed on Friday evening that discussions between the MHRA and trial sponsor King's College London would begin next week to address the wellbeing concerns. A government spokesperson emphasized that safety considerations remain paramount.
"We have always been clear about the red lines regarding this trial – ensuring the safety and wellbeing of the children and young people involved and always being led by the clinical evidence," the DHSC spokesperson stated.
The spokesperson added that preparations for the trial have been paused while the MHRA and clinical leaders work through these concerns, and that the trial will only proceed if expert scientific and clinical evidence concludes it is both safe and necessary.
Academic Institution's Position
A spokesperson for King's College London responded to the development, stating: "The wellbeing and health of young people with gender incongruence and their families has been, and will remain, our priority, and we will continue to work with the MHRA to support their further review of the trial."
The institution emphasized that the trial was designed by world-leading academics with scientific rigor at its core, and that ongoing scientific discussion is particularly important for complex clinical trials like Pathways.
Background and Context
The paused trial represents one of two studies announced to investigate the impact of puberty blockers following the Cass review in 2024. That review had recommended a ban on the medications, leading NHS England to announce that children with gender dysphoria would no longer receive puberty blockers as routine practice, with their use confined to research settings.
Dr. Hilary Cass, who led the original review, has previously commented on the evidence base for puberty blockers, stating that her report "uncovered a very weak evidence base" for their benefits for children and young people with gender dysphoria. However, she noted that "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."
Future Considerations
The MHRA's letter suggested a cautious approach moving forward, stating: "Future trials may consider lowering the threshold depending on the findings of the initial trial." This indicates that while the current trial faces significant hurdles, research in this area may continue with appropriate safeguards and age restrictions.
The development represents a significant moment in the ongoing debate about medical interventions for young people experiencing gender dysphoria, highlighting the tension between patient demand for treatments and regulatory concerns about long-term safety.
