UK Regulators Approve Modified PATHWAYS Trial Protocol with Minimum Age of 11 for Puberty Blocker Study
Key Insights
The MHRA and Health Research Authority (search) have approved a modified protocol for the PATHWAYS clinical trial investigating puberty-suppressing medication (search) in gender-incongruent youth.
A minimum participation age of 11 has been set, alongside strengthened safeguards for bone health, cognition, vaginal bleeding, and fertility preservation information.
Recruitment is not due to commence until 1 August 2026, pending ongoing legal proceedings from clinicians and campaigners challenging the trial's safety and ethics.
The Medicines and Healthcare products Regulatory Agency (search) (MHRA) has concluded its scientific dialogue with the trial sponsor on the PATHWAYS clinical trial, agreeing to a modified protocol that meets required regulatory standards. In parallel, the Health Research Authority (search) (HRA) has approved the trial for its ethical standards, clearing a path forward for the UK-wide study investigating the effects of puberty-suppressing medication (search) in children and young people experiencing gender incongruence (search).
The modified protocol introduces strengthened safeguards, including the establishment of minimum ages of entry to the trial and more clearly defined discontinuation measures around safety for bone health, cognition, and vaginal bleeding. Additionally, more detailed information for participants on fertility preservation has been incorporated.
As part of the scientific dialogue process, the MHRA sought the advice of independent experts from the Commission on Human Medicines (search) on participant safety and the adequacy of the proposed strengthened safeguards. The modified protocol was also submitted by the sponsor to the relevant Research Ethics Committee via the Health Research Authority (search).
Minimum Age and Eligibility Requirements
Gender-questioning children will need to be at least 11 years old to participate in the trial. The MHRA had previously suggested introducing a minimum age of 14 after raising safety concerns that led to the trial's pause in February 2026, when no minimum age had been set. Following discussions with the research team, a minimum age of 11 was agreed upon as part of a package of strengthened safeguards.
No child will be able to take part in the trial without parental consent, and young people must continue to meet all other eligibility criteria, including "demonstrating a good understanding of the intervention and its possible benefits and risks," according to the researchers. The trial is set to involve children under the age of 16 who are distressed about their gender and currently accessing gender services.
Trial Design and Objectives
The PATHWAYS clinical trial aims to provide evidence on how the timing of treatment affects quality of life, mental health, physical development, cognitive function, and gender-related distress. Researchers from King's College London lead the study, which was approved by UK regulators and ethics experts in November 2025.
The researchers stated that "there are no major changes to the design or conduct" of the trial beyond the strengthened safeguards. They added that they "always welcome scrutiny" of studies involving children and young people.
Legal Challenges and Recruitment Timeline
Recruitment to the PATHWAYS clinical trial is currently not due to commence until 1 August 2026, due to legal proceedings. Researchers from King's College London have agreed not to recruit participants until after this date to allow for legal proceedings to take place.
Ongoing legal action by some clinicians and campaigners questions the trial's safety and ethics. Campaigners claim the trial is unethical and that children cannot give fully informed consent to a treatment that might affect their future fertility.
Professor of Health Care Law at UCL, Prof Sir Jonathan Montgomery, commented: "Legal proceedings are expected to provide further scrutiny" of the trial, adding: "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."
Context: The Cass Review and Puberty Blocker Ban
Puberty blockers for people under 18 questioning their gender identity were banned in 2024. The drugs, also known as puberty suppressing hormones (PSH), are used to delay or prevent puberty from occurring. The ban followed a 2024 review by Dr Hilary Cass, which found that gender medicine had been operating on "shaky foundations" when it came to evidence for treatment, with concerns raised about the safety of puberty blockers.
Dr Cass has since stated it is "vital" that the trial for puberty blockers for under-16s goes ahead, warning that otherwise "we're going to have ongoing charlatans just handing out inappropriate drugs," pointing to the private sale of the drugs, particularly online.
A spokesperson for LGBTQ+ charity Stonewall said the group was "pleased" a modified protocol for the trial had been agreed. Many young people have been "left in limbo" since the 2024 ban, the spokesperson said, adding this has left them in "emotional and physical distress."