The Medicines and Healthcare products Regulatory Agency (MHRA) has cleared an investigator-led trial investigating puberty blockers in children and young people to continue.
The Phase III PATHWAYS trial (ISRCTN12491684), run by King’s College London (KCL), was paused in February 2026 after concerns were raised about the well-being of the participants in the study. The trial has generated a significant amount of controversy in the UK among the public.
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Now, the MHRA and KCL have concluded a scientific dialogue, and a modified protocol has been agreed upon as meeting the required regulatory standards. In parallel, the Health Research Authority (HRA) has approved the trial for its ethical standards.
A spokesperson from the PATHWAYS research team said: “We will always welcome scrutiny of research involving children and young people because their health and safety is paramount. Our priority remains to safely and robustly investigate the benefits and risks of puberty suppression for young people with gender incongruence to improve the evidence base and inform NHS healthcare.
“We have worked extensively and openly with the MHRA to understand and resolve the questions they raised about the PATHWAYS trial in February, which were not based on the emergence of any new scientific evidence. We have strengthened patient information connected to the trial and introduced a minimum age requirement; there are no major changes to the design or conduct of the PATHWAYS trial.
“Approval of the modified protocol paves the way for the study to begin, subject to the ongoing judicial review challenge to MHRA and HRA decisions, which focuses on their regulatory processes. As a research team, we will engage with this fully and openly”
The modified protocol includes strengthened safeguards, including the introduction of minimum ages of entry to the trial, which will be 11 for birth-registered females and 12 for birth-registered males. There is also a more clearly defined discontinuation measure around safety for bone health, cognition, and vaginal bleeding, as well as more detailed information for participants on fertility preservation.
As part of the scientific dialogue process, the MHRA sought the advice of independent experts from the Commission on Human Medicines on participant safety and the adequacy of proposed strengthened safeguards.
The modified protocol was also submitted by the sponsor to the relevant Research Ethics Committee, via the Health Research Authority.
Prof Sir Jonathan Montgomery, Professor of Health Care Law, at University College London (UCL), said: “It is good that the MHRA and HRA have completed their reviews of the scientific and ethical concerns that have been raised with them about the PATHWAYS clinical trial promptly. They have ensured that a modified protocol is in place prior to recruitment. It is encouraging that full regulatory oversight has been possible without unduly delaying the trial. Legal proceedings are expected to provide further scrutiny. It is to be hoped that the court will be able to reach a timely conclusion so that the legal status of the trial is confirmed before the anticipated date for commencement on 1 August. If there are legal issues that the regulators have overlooked, then it is in everyone’s interests that these are clarified as soon as possible.”
The study is investigating gonadotropin-releasing hormone analogues (GnRHa), including leuprolide acetate and triptorelin, in children and young people with gender incongruence.
The PATHWAYS clinical trial is a UK-wide clinical study investigating the effects of puberty-suppressing medication in children and young people who experience gender incongruence. It aims to provide evidence on how the timing of treatment affects quality of life, mental health, physical development, cognitive function, and gender-related distress.
Recruitment to the PATHWAYS clinical trial is currently not due to commence until 1 August 2026 due to legal proceedings.
Study to determine pathway for puberty blockers
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”.
At the time of the ban, TransActual, a UK organisation that provides information about trans rights and health matters, said: “Banning medicines with no evidence of serious harm, only for trans people, using powers designed for contaminated and life-threatening drugs, is discrimination plain and simple.”
This study will determine whether puberty blockers can be safely used in children and young people with gender incongruence.
