A groundbreaking clinical trial led by King’s College London (KCL) into the safety and effectiveness of puberty blockers has been paused after concerns were raised by a government watchdog.
The Pathways trial, which was launched in November last year, was paused after the Medicines and Healthcare Products Regulatory Agency (MHRA) flagged concerns about the welfare of young participants in the study.
In a letter sent to KCL, the regulator called on the study’s sponsors to limit participation to those aged 14 and over, noting that young people may sometimes be unable to understand the complexity of such long-lasting treatments.
It also highlighted concerns about additional effects of GnRH – a puberty blocker that is to be investigated in the study – such as posing possible long-term risks like reductions in fertility.
On 29 May 2024, the government even introduced emergency restriction on the sale and supply of GnRH analogues when they are used to suppress puberty. The Cass Review highlighted that the quality of evidence for prescribing GnRH analogues to suppress puberty is poor and the risk of short or long-term harm is unclear.
In response, a MHRA spokesperson commented that “the MHRA is applying the highest scrutiny and taking a cautious and measured approach” to the study, relying on the “best scientific evidence”.
‘Scientific dialogue will now follow’
The Pathways trial was commissioned last year by the since-dissolved NHS England and is being led by researchers from King’s College London in conjunction with the South London and Maudsley NHS Foundation Trust.
It plans to involve 226 participants under the age of 16 who have diagnoses of gender incongruence, have reached puberty and have already received gender-related care – this doesn’t include young people who have already been given GnRH.
Puberty blockers are drugs that slow or prevent puberty from occurring. They were banned in 2024 for under-18s following a consultation and advice from the Commission on Human Medicines, where their usage was branded a “scandal”. The expert group said prescribing the drugs to children for gender dysphoria was an “unacceptable safety risk”.
The MHRA, Department for Health and Social Care (DHSC) and King’s have all said they will continue to engage in “scientific dialogue” pending the outcome of these concerns.
On Friday, the DHSC said that the “trial will only be allowed to go ahead if the expert scientific and clinical evidence and advice conclude it is both safe and necessary”.
‘Lack of evidence’
The study’s strict inclusion criteria echo the findings of the Cass Review published in 2024 which made a series of recommendations regarding the NHS’ treatment of gender in children and young people.
Hilary Cass, who led the Review, raised concerns about the “lack of evidence” on the long-term impact of puberty blockers, stating that “research has let us all down”. She called for additional research into the drugs’ effects, of which the Pathways trial is a part of.
The clinical trial has been politically charged from inception and follows intense controversy around the use of puberty blockers for under-18s by the NHS, particularly in the now-closed Gender Identity Development Service.
In December last year, Streeting resisted calls from opponents to pause the trial, claiming he was following “clinical advice” in an “extremely sensitive area”. In January, a number of clinicians raised concerns about the trial and an online petition to cancel it has since garnered over 140,000 signatures.
The trial’s investigators have argued that the data produced is necessary to fill gaps in the evidence base surrounding puberty blockers. Cass has since defended the trial:
“…if the study doesn’t go ahead and families continue to vote with their feet – as they are at present – large numbers of children and young people will continue to get a range of inappropriate, dangerous, and/or unmonitored medications online and from unregulated providers.”
A spokesperson for King’s College London said, “The wellbeing and health of young people with gender incongruence and their families has been, and will remain, our priority, and we will continue to work with the MHRA to support their further review of the trial, which has been designed by world-leading academics with scientific rigour at its core.”
“That rigour and ongoing scientific discussion is important for any clinical trial, particularly one as complex as Pathways, which aims to build an evidence base that can help young people and clinicians to make better-informed decisions in the future.”
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