UK Regulator Pauses PATHWAYS Puberty Blocker Trial Over Safety Concerns

The preliminary work in establishing the PATHWAYS clinical trial into the prescription of puberty blockers for children and young people with gender incongruence has been paused, following new concerns raised by the medicines regulator, the MHRA. The trial will not start to recruit until issues raised by MHRA have been resolved between the regulator and the trial clinicians.

The Phase III PATHWAYS trial (ISRCTN12491684), sponsored by King's College London, is investigating gonadotropin-releasing hormone analogues (GnRHa), including leuprolide acetate and triptorelin, in children and young people with gender incongruence. The study was set to enrol approximately 226 children between 11 and 15 years of age; however, the MHRA has suggested the minimum age of enrolment should rise to 14 years of age.

Discussions between the MHRA and the trial sponsor will begin next week to address the new concerns. A Department of Health and Social Care spokesperson said: "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. As the evidence is now being interrogated by clinicians, preparations for the trial have been paused while the MHRA and clinical leaders work through these concerns."

The study involves children who are distressed about their gender and currently accessing gender services, examining the impact of the puberty blockers on their physical, social and emotional wellbeing.

An MHRA spokesperson commented: "With all complex clinical trials, MHRA's top priority is the safety and wellbeing of the trial participants. It is part of the usual process that clinical trials are kept continuously under review and for us to have active scientific dialogue with the trial sponsors. The safety and wellbeing of the participants to be recruited into the PATHWAYS clinical trial is paramount, particularly in view of the age of the children and young people who may be involved. For this reason, the MHRA is applying the highest scrutiny and taking a cautious and measured approach."

The Department of Health and Social Care stated: "This trial will only be allowed to go ahead if the expert scientific and clinical evidence and advice conclude it is both safe and necessary. The safety and wellbeing of children and young people have always been the driving consideration in every decision we have made regarding this trial and always will be."

In the UK, puberty blockers for people under-18 were banned in 2024 after the Cass Review. The Commission of Human Medicines (CHM) provided an independent report on the continued prescribing of puberty blockers in children to the government, concluding there is "currently an unacceptable safety risk".