Puberty blockers trial paused after MHRA raises safety concerns

A clinical trial into the prescription of puberty blockers for children and young people questioning their gender has been paused after the medicines regulator raised safety concerns.

Discussions between the Medicines and Healthcare products Regulatory Agency (MHRA) and the trial sponsor, King’s College London, will begin next week to address the new concerns.

The PATHWAYS trial – which was announced on 7 November 2025 after getting approval from the MHRA and the Health Research Authority – will not begin recruiting participants until these issues have been resolved.

The trial is a UK-wide clinical study involving 226 participants under the age of 16 who are experiencing gender incongruence, which can cause significant emotional distress.

The medication being assessed is a gonadotropin-releasing hormone analogue (GnRHa), which temporarily pauses puberty, and the trial will assess the children’s quality of life, mental wellbeing, physical development, cognitive function, and gender-related distress over a two-year period.

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The MHRA expressed concern over the current age limit for participants in the trial in a letter, published on the government website on Friday.

The letter said: ‘Since potentially significant and, as yet, unquantified risk of long-term biological harms is present to participants … at the very least, there should be a graded/stepwise approach starting with those aged 14 as the lower limit of eligibility.’

The upper age limit for participants is 15 years and 11 months. There is not current lower limit because eligibility is determined by a person’s pubertal stage not their age.

However, King’s College London said it is ‘very unlikely’ that many children under the age of 11 will show the necessary level of understanding of the treatment to take part.

The MHRA also called for a ‘much more detailed’ physiological safety assessment for the children involved – including more detailed monitoring of bone density and blood health, and a more rigorous consent process for participants.

‘Reduction in gametogenesis – [the formation of sex cells] – will very likely cause infertility in these young people. In light of the long term fertility consequences, Gillick Competence for consent … should be sought,’ the letter added.

Gillick competency is used to assess whether a child is mature enough to consent to treatment.

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An MHRA spokesperson said: ‘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.

‘We have raised some concerns related to the wellbeing of participants and scientific dialogue will now follow with the trial sponsor. We rely on the best scientific evidence to ensure all trials are as safe as possible for those participating.’

A Department of Health and Social Care spokesperson added: ‘We have always been clear about the red lines regarding this trial – ensuring the safety and wellbeing of the children and young people involved and always being led by the clinical evidence.

‘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.

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‘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.’

Puberty blockers for people under-18 questioning their gender identity were banned following the Cass Review in March 2024.

The Cass Review concluded that children and young people seeking NHS care for gender-related distress had been let down by the ‘remarkably weak evidence base’.