London – A pivotal clinical trial investigating the apply of puberty blockers in children experiencing gender dysphoria has been paused by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). The decision, announced Friday, stems from safety concerns regarding potential long-term health impacts and focuses on the age of participants eligible for the study. This pause adds another layer of complexity to an already highly sensitive and debated area of healthcare, following a comprehensive review of gender identity services for children led by Dr. Hilary Cass.
The trial, known as Pathways, aimed to gather robust evidence on the physical, social, and emotional effects of puberty blockers – medications that temporarily suppress the development of secondary sexual characteristics – in young people grappling with gender incongruence. With plans to recruit over 220 participants aged between approximately 11 and 15, the study was heralded as a crucial step towards establishing an evidence base to inform clinical practice. However, the MHRA has now raised concerns about the minimum age threshold, suggesting it be increased to 14, and has called for more detailed monitoring of bone density and a more rigorous consent process. The move underscores the growing scrutiny surrounding the use of these medications, particularly given the limited long-term data available.
This pause comes after puberty blockers were banned for under-18s in the UK in 2024, except within the context of clinical research trials. The decision to halt recruitment to the Pathways trial highlights the ongoing tension between providing access to potentially beneficial treatments and ensuring the safety and wellbeing of vulnerable young people. The MHRA’s intervention reflects a cautious approach, prioritizing a thorough assessment of potential risks before proceeding with a study involving children.
Concerns Over Long-Term Effects Prompt Regulatory Review
The core of the MHRA’s concern lies in the “potentially significant and, as yet, unquantified risk of long-term biological harms” associated with puberty blockers, as stated in a letter to King’s College London, the trial sponsor. The agency emphasizes that the biological safety of these medications has not been definitively demonstrated in the proposed cohort of young participants. This concern is particularly acute given the irreversible nature of some of the changes that puberty blockers may prevent. The MHRA’s letter advocates for a “graded/stepwise approach,” beginning with participants aged 14 and above, allowing for a more cautious evaluation of the risks and benefits.
The Pathways trial was designed as a response to recommendations made in the independent review of gender identity services for children and young people in England, led by Dr. Hilary Cass. The Cass review, published in 2024, highlighted a “weak evidence base” supporting the benefits of puberty blockers for young people with gender dysphoria. Dr. Cass acknowledged the passionate beliefs held by clinicians, families, and individuals regarding the potential benefits of these medications, but emphasized the need for rigorous research to clarify their efficacy and safety. The trial was intended to address this evidence gap, but the MHRA’s intervention underscores the complexities involved in conducting such research.
The Cass Review and Shifting Landscape of Gender Care
The Cass review was commissioned in 2020 following concerns about the rising number of children and young people seeking gender identity services and the lack of robust evidence to guide clinical decision-making. The review examined the quality of research, the clinical pathways available, and the experiences of young people and their families. Its findings led to significant changes in the provision of gender identity services in England, including the decision to restrict access to puberty blockers outside of research settings. The review concluded that the current approach to gender care for young people was not sufficiently evidence-based and that there was a need for a more cautious and holistic approach.
Following the Cass review, NHS England announced that children with gender dysphoria would no longer receive puberty blockers as a routine treatment. The medications would only be available within the context of clinical research trials, such as the Pathways study. This decision reflected a growing consensus that more research was needed to understand the long-term effects of puberty blockers and to ensure that young people were receiving the best possible care. The pause of the Pathways trial, represents a further step in this evolving landscape.
King’s College London Responds to MHRA Concerns
King’s College London, the institution leading the Pathways trial, has affirmed its commitment to the wellbeing of young people with gender incongruence and their families. A spokesperson for the college stated that they will continue to work closely with the MHRA to address the concerns raised and support the agency’s review of the trial protocol. They emphasized that the trial was designed with “scientific rigour at its core” and that ongoing scientific discussion is crucial for building an evidence base to inform clinical decision-making. The college acknowledged the complexity of the research and the importance of ensuring the safety and wellbeing of all participants.
The trial had initially planned to recruit an estimated 226 young people over a three-year period. The youngest participants were expected to be between 10 and 11 years old for biological females and 11 to 12 years old for biological males, although researchers anticipated that the rigorous selection process would likely result in older participants being enrolled. The MHRA’s request to raise the minimum age to 14 represents a significant adjustment to the trial protocol and will likely impact the recruitment process.
International Context: Modern Zealand’s Approach
The UK’s pause of the Pathways trial is not an isolated event. Other countries are as well grappling with the complexities of providing gender identity care to young people. In November 2025, New Zealand announced a ban on new prescriptions of puberty blockers for young transgender people, citing concerns about the lack of long-term evidence and the potential for irreversible effects. This decision reflects a growing trend towards a more cautious approach to the use of these medications, particularly in light of the evolving evidence base.
What Happens Next?
Discussions between the MHRA and King’s College London are scheduled to begin next week to address the concerns raised and determine the next steps for the Pathways trial. The recruitment process will remain paused until these issues are resolved. The outcome of these discussions will be critical in determining whether the trial can proceed, and if so, under what conditions. The MHRA has made it clear that the trial will only be allowed to continue if the expert scientific and clinical evidence and advice conclude that it is both safe and necessary.
Professor Sir Jonathan Montgomery, a professor of health care law at University College London, emphasized that the MHRA’s intervention is a sign of a robust regulatory process working in the interests of participants. He clarified that the discussions are intended to strengthen the trial protocol, not to halt it altogether, and that the concerns are scientific in nature, not driven by legal challenges.
The ongoing debate surrounding puberty blockers highlights the need for continued research and a nuanced approach to gender identity care. Balancing the potential benefits of these medications with the need to protect the wellbeing of young people remains a significant challenge for healthcare professionals and policymakers alike. The outcome of the Pathways trial, and similar research efforts around the world, will be crucial in informing future clinical practice and ensuring that young people receive the best possible care.
The next update from the MHRA regarding the Pathways trial is expected following the discussions with King’s College London next week. We will continue to monitor this developing story and provide updates as they become available. Your thoughts and perspectives on this important issue are welcome in the comments below.
Keep reading