UK puberty-blocker Pathways trial paused

Britain’s flagship attempt to generate hard evidence on puberty blockers in paediatric gender medicine has been put on ice before enrolling its first patient. The Pathways clinical trial, sponsored by King’s College London, has paused recruitment after the Medicines and Healthcare products Regulatory Agency (MHRA) warned that the protocol should set a minimum participant age of 14 due to “unquantified risk” of “long-term biological harms,” according to The Guardian.

The trial was conceived in the wake of the Cass Review, which concluded that the evidence base supporting puberty-suppressing gonadotropin-releasing hormone (GnRH) analogues for gender dysphoria in children is “poor.” Cass’s logic was: if clinicians and families are making high-stakes claims about benefits, then a controlled trial is the only way to measure them. Pathways was expected to recruit roughly 226 young people over three years, with initial plans allowing enrolment as young as 10–11 for natal females and 11–12 for natal males, The Guardian reports.

The MHRA’s letter, cited by both The Guardian and the Evening Standard, does not merely request a paperwork tweak. It argues for a “graded/stepwise approach” starting at age 14, with any future lowering of the threshold contingent on initial findings. That is a regulator effectively saying: we do not know the biological safety profile in early puberty, and you do not get to find out by starting with the youngest cohort.

The Department of Health and Social Care said “scientific dialogue” will follow and the trial will proceed only if expert advice concludes it is “safe and necessary,” per The Guardian. King’s College London said it would work with MHRA and defended the protocol’s “scientific rigour.”

The pause implies missing data—precisely the data that would justify exposing children to endocrine disruption. A meaningful risk assessment would normally specify: (1) dose and duration distributions, (2) primary and secondary endpoints, (3) statistical power for clinically relevant effect sizes, and (4) long-term follow-up plans. For puberty blockers, the unresolved questions are not rhetorical. They include bone mineral density trajectories (and whether catch-up occurs), neurocognitive development, cardiometabolic markers, and fertility-related endpoints (including the feasibility and uptake of preservation). If these are “unquantified,” the trial’s initial design has not persuaded the regulator that it can quantify them safely.

The Evening Standard notes the pause also follows legal action supported by campaigners including J.K. Rowling, who called the trial unethical because children cannot give meaningful consent. One can debate the celebrity cameo, but the point remains: the state commissioned a review that demanded better evidence, then tried to generate that evidence, and now the state’s own regulator is warning that the very population where the intervention is most politically salient is too risky to study first.

If Pathways restarts with older adolescents, the trial may become more ethically and regulatorily palatable—while simultaneously becoming less informative about the early-puberty use that drove the controversy. The precautionary principle may end up rewriting the research question.