Safety of prescribing puberty blockers

CHM have been clear in their view that the current prescribing and care pathway for gonadotropin-releasing hormones (GnRH) agonists for gender incongruence and/or gender dysphoria in children represents an “unacceptable safety risk”. That is why their first recommendation was that an indefinite ban on prescribing of these medicines for these purposes to patients under 18 should be enacted by ministers.

Improving the prescribing environment

Regarding the safety of the prescribing environment, CHM has recommended that:

• the restrictions in the temporary prohibition order should continue indefinitely for prescribers registered outside the UK
• there should be a review of the order in April 2027 for prescribers who are registered to practise in the UK
• a risk acknowledgement form should be developed for use with patients and/or parents or carers
• a common care standard for specialist gender services is developed for children and young people
• there should be a funded strategy for capturing and reporting long term safety and efficacy data across all UK gender specialist services

Prescribing to under 18s

CHM state in their report that off-label prescribing of these medicines to under 18s for gender incongruence and/or gender dysphoria by appropriately trained and resourced clinicians should only take place once their recommendations to enact a safe prescribing environment (recommendation 3) have been delivered. The government is committed to implementing that recommendation, and progress will be reviewed in 2027.

Off-label prescribing

Medicine manufacturers apply to the Medicines and Healthcare products Regulatory Agency (MHRA) to have their medicine licensed in the UK for use in specific clinical conditions and at specific doses. A medicine will only be licensed if there is sufficient evidence to show it is safe and effective for that use. ‘Off-label’ prescribing means the person prescribing the medicine is using it for a different purpose or at a different dose to that specified in the licence.

CHM also identify in their report that clinicians prescribing off-label use of medicines typically have to rely on less systematic or comprehensive evidence than that required for licensing approval of a medicine: for example, there will often be no or limited high quality clinical trial evidence to support its use.

Off-label use may rely on evidence available for a similar indication - for example, a painkiller, licensed for use in adults, may be prescribed off label by a clinician for a child. There may not be any specific clinical trial evidence regarding the use of the medicine in children for pain relief, but the purpose is the same and the clinician will use their professional knowledge to judge the differences between an adult and a child and what this means for the treatment’s likely safety and effectiveness.

The use of puberty blockers in the treatment of gender incongruence and/or gender dysphoria is different to their licensed use for treating precocious puberty (in young children) and for certain cancers (in older people), and the treatment effectiveness and safety considerations are also different. The normal physiological process of puberty is very complex, including maturing of brain functions as well as physical development. Although CHM did identify evidence that already exists about risks to bone health and fertility in young people associated with puberty suppressing treatments, for patients who are at different stages of life (young children or older adults), the considerations will be different. The wider risks and benefits of taking puberty blockers at this important developmental stage are not well understood. More evidence is therefore needed. It is right that in this instance a clinical trial is being planned to properly study the effect of puberty blockers specifically for children and young people with gender incongruence and/or gender dysphoria to establish the evidence for their efficacy and safety.

A limited evidence base would not always preclude off-label use, but CHM saw evidence that raised clear safety risks to children and young people, including poor medical and prescribing practice that did not fulfil expectations for consent, safe prescribing practice or clinical practice as set out in General Medical Council (GMC) guidance.

See further guidance on:

• consent - Brief guide: capacity and competence to consent in under 18s (Care Quality Commission) (PDF, 81KB)
• prescribing - Good practice in proposing, prescribing, providing and managing medicines and devices (GMC)

Use of puberty blockers for other medical conditions

Both Baroness Cass and the independent CHM found that there is a lack of evidence for the efficacy of these medicines in the treatment of gender incongruence and/or gender dysphoria, and that there is currently an unsafe prescribing environment.

Medicines are only licensed for specific purposes, and access may require patients to meet specific criteria. The new weight loss medicines are a recent example of this  - patients have to be above a certain body mass index (BMI), and there are also qualifying criteria around co-morbidities (where a patient has multiple health conditions which may interact with each other) before they can be accessed in the NHS for weight loss purposes.

In the case of GnRH agonists, they are licensed for the treatment of specific disorders in children where puberty begins too early (precocious puberty). This is not related to gender identity, but is to treat a well understood physical illness and is intended to enable the child to delay the early onset of puberty and then experience a normal puberty at the normal time. Use in the context of gender incongruence and/or gender dysphoria is to have the effect of disrupting (and potentially never completing) the normal puberty process and the evidence relating to the long term effects of that is limited.

The legislation, which followed CHM’s report, ensures that children and young people are protected from unsafe prescribing practice, including from prescribers registered outside the UK, that are going far beyond the normal realm of off-label prescribing.

The government prepared and published a detailed equality and health inequalities impact assessment (available on the consultation page) to inform its decision making around curtailing access to GnRH agonists, including a consideration of the impact to children and young people who may have the protected characteristic of gender reassignment.

Requirements for clinical practice

Clinicians have the full support of the government, especially those working to care for children and young people with complex needs.

CHM have been clear in their report that they saw evidence of unsafe prescribing, and that an indefinite order was justified to stop that, until a safe prescribing environment can be established. They further recommended that a permanent ban on recognition of prescriptions for these medicines from prescribers who are not registered in the UK should be enacted, as they are outside the reach of UK regulators.

The National Institute for Health and Care Excellence (NICE) has been asked by ministers to develop, by 2027, UK-wide standards for all clinicians to follow, and for a safer prescribing environment to be established. MHRA has been asked to develop a risk acknowledgement form for use with patients and/or parents or carers.

Clinicians are still able to prescribe these medicines for their licensed indications, and young people who were already taking the medication before the first emergency order for gender incongruence and/or gender dysphoria can continue their prescriptions, as long as they are now issued by a UK prescriber.

It is also important to note that clinicians outside of specialist gender services cannot initiate puberty blockers as a treatment for children and young people for gender incongruence and/or gender dysphoria, although they can still continue prescribing for those who started before the ban came into effect.

CHM’s views on the proposed clinical trial

Any clinical trial requires a rigorous process of development and approvals, including ethical review, before it can go ahead, and this is especially important in any trial involving children and young people.

In their role providing independent advice for ministers, CHM was provided with information on the proposed clinical trial into puberty blockers being developed by NHS England and the National Institute for Health and Care Research (NIHR).

As the trial was still in development, the information CHM received reflected an interim proposal that was subject to further development and the approvals process being completed.

CHM recommended (recommendation 7) that any trial provide an ‘off ramp’ to provide children and young people still at pubertal age when they completed the trial with continuing puberty blockers.

This has been considered by the trial development team, and will form part of the proposal’s final review and approval stages, including ethical review. As of January 2025, the study team’s application for funding is going through all the usual review and approval stages, including peer review and NIHR funding committee consideration, and full ethical approval processes ahead of set up.

Trial participation and timing

Better-quality evidence is critical if the NHS is to provide reliable, transparent information and advice to support children and young people, and their parents and carers, in making potentially life-changing treatment decisions.

That is why the government is supporting NHS England to set up what would be a world leading study into the potential benefits and harms of puberty suppressing hormones as a treatment option for children and young people with gender incongruence and/or gender dysphoria.

The trial aims to begin recruiting in early 2025.

It is important to give children and young people the opportunity to take part in research that may improve or increase knowledge about childhood conditions and their treatment. This is essential to ensure they can benefit from new interventions designed for their needs.

Research with children and young people, as with all research involving human participants, must ensure that:

• there is an acceptable balance of risk and benefit
• approval is obtained from an independent research ethics committee
• informed consent or assent is secured from participants and/or their parents or carers

Specific ethics principles apply to research with children and young people  - for example, research should only include children and young people where the relevant knowledge cannot be obtained by research in adults, and research aims must be relevant to child health and/or wellbeing.

Timing of publication of CHM’s report

CHM drafted their report for consideration by the Secretary of State for Health and Social Care and Minister of Health for Northern Ireland as required in legislation when making a decision to make an order under section 62 of the Medicines Act 1968. That decision was enacted in December 2024.

Due to the public interest in this legislation the Secretary of State has made the decision to publish the report in the interests of transparency and openness. Time has also been taken to develop an accessible version of the report for publication.

Progress against CHM and Cass recommendations

The government is taking forward CHM’s recommendations with regulators and the devolved governments. The legislation will be reviewed in 2027.

The government and NHS England have made a clear commitment to implement the Cass Review in full.

In line with this commitment, NHS England has opened 3 new children and young people’s gender services in:

• the North West
• London
• the South West (Bristol)

These new services offer a fundamentally different clinical model, embedding multidisciplinary teams in specialist children’s hospitals. This model includes a nominated paediatrician or psychiatrist with overall clinical responsibility for patient safety in these services.

A fourth service will open in the East of England in spring 2025. NHS England is making progress towards its commitment for there to be a specialist children’s gender service in every region by 2026.

In addition to the expansion of these services, NHS England has published a new service specification for the National Referral Support Service for specialist services for children and young people with gender incongruence. This means that a referral for the specialist children and young people’s gender service can be only made by an NHS-commissioned, secondary care-level paediatric service or a children and young person mental health service. This will help ensure that healthcare professionals with the relevant expertise conduct the assessment and help determine any co-existing mental health or other health needs of these children and their onward care.

NHS England’s ambitious 2-year action plan to implement the Cass Review sets out how it will continue to transform and improve services, helping to tackle waiting lists while ensuring safe and holistic care.

Mental health support for children and young people

NHS England has written to all children and young people on the children and young people’s gender service waiting list before 1 September 2024 to offer them a mental health appointment.

In line with NHS England’s new referral pathway, those who are referred from 1 September 2024 will first be seen by secondary care and will be assessed by NHS paediatric teams or mental health services. This will ensure their needs are met holistically.

Those who are not on the waiting list and are affected by the banning order are able to access NHS mental health services through a dedicated single point of contact (SPOC).

The SPOC can be contacted by email at agem.cyp-gnrss@nhs.net or by calling 0300 131 6775 and selecting option 3.

Developing further information about the ban

Ministers agree with recommendation 8 of the CHM report, which states:

An ongoing co-produced patient and/or parents or carers, and GP communication strategy should be prepared by DHSC working in collaboration with the 4 UK health services. This should include a plan detailing the timetable for enacting all the accepted CHM recommendations. The importance of further research in this area to understand the long term efficacy and safety of the GnRH agonists should also be included in the communications plan.

Ministers will be collaborating across the 4 UK health services to take this forward.

Government response to consultation submissions

The government carefully considered all of the submissions that were made during the process of consultation.

In addition to those responses, CHM advised the Secretary of State that the current prescribing environment is unsafe, and that the ban should remain indefinitely to allow time to address that, with recommendations as to how that should be done.

Separately, the Cass review was informed by a large range of sources, including extensive stakeholder engagement of over 1,000 individuals. It met regularly with support and advocacy organisations with a primary or significant goal of supporting gender-questioning young people, and found that that there is a lack of evidence for the efficacy of these medicines in the treatment of gender incongruence and/or gender dysphoria.