UK Clinical Trial on Puberty Blockers Halted Over Safety Concerns

A clinical trial investigating puberty blockers for children has been paused due to concerns raised by the Medicines and Healthcare products Regulatory Agency (MHRA). The regulator recommended establishing a minimum age limit of 14 years, citing “unquantified risks” of potential long-term biological harms associated with the medication.

The Department of Health and Social Care (DHSC) announced the pause on November 3, 2024, stating that discussions between the MHRA and the trial sponsor, King’s College London, are set to begin next week. The Pathways clinical trial will not commence recruitment of participants until these concerns are addressed.

The trial was initiated following recommendations from the Cass review, which assessed children’s gender care. The review concluded that the existing research supporting the benefits of puberty blockers for children experiencing gender dysphoria was of “poor” quality. Led by Hilary Cass, the review pointed out a “very weak evidence base” for the medication’s benefits, suggesting a trial was necessary to provide clarity.

A spokesperson for the DHSC emphasized their commitment to the safety and wellbeing of children involved in the trial, stating, “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 MHRA raised new concerns through a letter, urging that the trial’s eligibility age be adjusted. The letter highlighted the need for a “graded/stepwise approach” starting with participants aged 14, as the risks of long-term biological harms remain uncertain. The agency indicated that future trials might reassess this threshold based on the outcomes of the initial study.

King’s College London responded by affirming their dedication to the health of young people experiencing gender incongruence. They stated, “The wellbeing and health of young people with gender incongruence and their families has been, and will remain, our priority.” The institution plans to collaborate with the MHRA to facilitate further review of the trial.

Initially, the clinical study aimed to recruit approximately 226 participants over three years, with the youngest candidates being 10 to 11 years old for biological females and 11 to 12 for biological males. However, the research team indicated that the rigorous selection process would likely result in older participants.

The MHRA expressed concerns regarding the existing age limit of the trial, which currently allows participants as young as 10. The regulatory body stated that biological safety has not been definitively demonstrated for this age group, necessitating a cautious approach.

This paused trial is one of two studies focusing on the effects of puberty blockers, with the Cass review recommending a ban on their use outside of research contexts. Following this guidance, NHS England announced that children with gender dysphoria would no longer receive puberty blockers as a standard treatment, restricting their use to research settings only.

As discussions continue between the MHRA and King’s College London, the future of the Pathways clinical trial remains uncertain, pending the resolution of safety concerns and the establishment of a robust evidence base for the use of puberty blockers in children.