A clinical trial assessing the risks and benefits of puberty blockers for children questioning their gender identity has been paused, raising further scrutiny of the medications and the care pathways for young people experiencing gender dysphoria. The pause was initiated by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) due to safety concerns, specifically regarding the potential for “long-term biological harms.”
The trial, known as Pathways, had been set to recruit over 220 children aged between approximately 11 and 15. Researchers at King’s College London were leading the study, which aimed to examine the physical, social, and emotional impacts of puberty blockers. However, the MHRA has now requested a revision to the trial protocol, suggesting a minimum age limit of 14 for participants, an increase from the originally approved range of 10-15.
This pause follows a period of increasing debate and legal challenges surrounding the use of puberty blockers in young people. In 2024, puberty blockers were banned for under-18s in the UK outside of a research setting. The medications, also referred to as puberty suppressing hormones (PSH), work by temporarily halting the physical changes of puberty, allowing young people time to explore their gender identity.
The MHRA’s concerns, outlined in a letter to King’s College London, center on the lack of definitive data regarding the long-term safety of these drugs, particularly in younger adolescents. The agency emphasized the need for a “graded/stepwise approach,” beginning with participants aged 14 and above. They also called for more detailed monitoring of bone density and a more rigorous consent process to ensure participants fully understand the potential risks and benefits.
The decision to pause the trial comes after the publication of the Cass Review in 2024, an independent review of gender identity services for children and young people in England. Dr. Hilary Cass, who led the review, found a “weak evidence base” supporting the benefits of puberty blockers for this population. While acknowledging the passionate beliefs of clinicians, families, and young people who have experienced positive effects, the review concluded that a clinical trial was necessary to establish a more robust understanding of the medications’ impact.
A spokesperson for the Department of Health and Social Care affirmed that the safety and wellbeing of children and young people remain the paramount consideration. They stated that the MHRA’s concerns are being taken seriously and that scientific dialogue with King’s College London is underway. The trial will only proceed if expert scientific and clinical advice confirms its safety and necessity.
King’s College London acknowledged the MHRA’s concerns and reiterated its commitment to the wellbeing of young people with gender incongruence. The institution emphasized the scientific rigor of the trial design and its intention to collaborate with the MHRA to address the identified issues. They stated that ongoing scientific discussion is crucial for any clinical trial, particularly one as complex as Pathways.
The Pathways trial was one of two studies announced to investigate the impact of puberty blockers, following the recommendations of the Cass Review and the subsequent changes to NHS England’s approach to gender care. NHS England now restricts the routine use of puberty blockers, confining their administration to research settings.
Professor Sir Jonathan Montgomery, a professor of health care law at University College London, emphasized that the MHRA’s actions demonstrate a functioning regulatory process focused on participant safety. He clarified that the discussions are intended to strengthen the trial protocol, not to halt it entirely, and that the concerns raised are scientific in nature, not a result of legal challenges.
The pause in the Pathways trial underscores the evolving understanding of puberty blockers and the complexities surrounding gender care for young people. While the medications can provide valuable time for exploration and decision-making, the potential for long-term effects necessitates careful consideration and robust research. The MHRA’s intervention highlights the importance of prioritizing safety and ensuring that any clinical intervention is supported by a strong evidence base.
The outcome of the discussions between the MHRA and King’s College London will determine the future of the Pathways trial and potentially influence clinical practice regarding the use of puberty blockers for young people experiencing gender dysphoria. Further updates will be provided as the situation develops.
