An Ethical Design for the UK’s Puberty Blocker Trial?

How should new research into gender interventions on children take place?

Photo by Emily Morter on Unsplash

Britain’s National Health Service (NHS) proposes to inject a new cohort of gender dysphoric children with powerful gonadotropin-releasing hormone agonists (GnRH agonists), known colloquially as puberty blockers. These off-label drugs are more typically used in the treatment of life-threatening diseases such as adult prostate cancer.

In December 2024, Genspect UK called on the British government to stop this puberty blocker trial until, at the very least, a non-medical intervention protocol was designed and data on patient outcomes was available from the linkage of child and adult gender clinic records, as proposed in Recommendation 5 of the Cass Review. Paragraph 15.63 of the Cass Review makes clear that NHS gender clinics had withheld the relevant data from Dr Cass and her team. The usefulness of any patient data that the clinics retained remains to be seen.

Perhaps in reaction to criticism of previous puberty blocker experiments at the disgraced Gender Identity Development Service (GIDS), part of the Tavistock and Portman NHS Foundation Trust based in London, it has been announced that the subjects of the new NHS puberty blocker trial would also receive psychosocial support¹

Any first-year student of science should know that a robust experiment cannot manipulate two variables simultaneously - in this case, puberty blockers and psychosocial intervention - in the same group of test subjects, if we wish to know which variable caused the recorded outcomes. The limited information available on this study includes no mention of a control group, which should also cast the validity of the new experiment into doubt.

The apparent lack of a valid experimental design and the rush for the NHS to recruit a new cohort for puberty blocker prescriptions suggests that the NHS 'trial' being organised by the Children and Young People’s Gender Dysphoria Research Oversight Board could be an attempt to resurrect the discredited 'Dutch protocol' under the guise of research.²

There is no ban on puberty blockers

You may have seen media reports and statements by politicians about a ban on puberty blockers in the UK, but this was never the case. Because gender is political, we need to look at these claims in detail to establish what happened with the British government and that country's health service, regarding policy and legislation on these particular drugs.

The original announcement in March 2024 that the NHS would not routinely prescribe puberty blockers was not in fact a policy change. As far as we know, these GnRH agonist prescriptions for gender dysphoria were only available on the NHS from the hospitals affiliated with the GIDS clinic at the Tavistock and Portman NHS Trust in London and its satellite clinic in the northern English city of Leeds. GIDS also had regional teams focused on patients in the Midlands and south-west of the country.

Even so, Appendix 8 to the Cass Review shows that only a minority of GIDS patients were referred to hospital endocrinology departments. Page 7 of 'The Gender Identity Development Service Audit Report', produced by NHS Arden and Greater East Midlands Commissioning Support Unit in June 2023, states that at GIDS: “34.6% of natal males were referred to endocrinology, compared to 24.2% of natal females. Of the total patients referred into endocrinology, 34% were natal male, and 66% natal female.” This discrepancy occurred because female patients significantly outnumbered males.

Many on the gender critical side of the non-debate around childhood transition assumed the March 2024 NHS announcement meant puberty blockers would no longer be prescribed, but that was never the case. Existing prescriptions of GnRH agonists continued, and the BBC reported at the time that doctors could apply for new prescriptions as required.³

When the previous Conservative government of the UK implemented emergency legislation regulating the supply of GnRH agonists from private and overseas clinics, there was similar optimism that this amounted to a ban, but that wasn't true either. The latest temporary legislation (https://www.legislation.gov.uk/uksi/2024/1319/contents/made) extends regulations for private and overseas clinics to a review taking place no later than 1st October 2027. In content, it is very similar to the previous emergency legislation deployed by the former government.

Of note, all NHS prescriptions for whatever purpose are explicitly exempt from these puberty blocker regulations, in Article 5. While puberty blockers are not a routine NHS treatment for gender dysphoria, as this use was always experimental and was not generally available from local hospitals or family doctors, there is nothing in either UK legislation or government policy to stop the NHS carrying out a non-routine implementation. And so, a new NHS trial of puberty blockers was announced for 2024, now pushed back to recruitment of child patients in early 2025.

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How should this study work?

Before any more children are put at risk of harm by experimental treatments with a weak evidence base, as highlighted in paragraph 24 of the Cass Review, we need proper, reliable and impartial research on elective gender interventions. Even if Genspect UK and its supporters are successful in persuading the NHS to pause the current trial, it would be untenable to argue that there should be no further research on this subject while children continue to be injected with puberty blockers and cross-sex hormones in the UK and around the world.

It has been obvious to many that a double-blind randomised control trial, the gold standard for medical experiments, would not be possible in the case of puberty blockers. The profound effects of disrupting puberty and the lack of effects from a placebo, noticed by study participants, could influence test subjects in both intervention and control groups, biasing the result. The children who were and were not administered puberty blockers would also be obvious to the clinicians running the study, introducing a further source of bias.

Because they do not have financial or ideological investment in the prescription of puberty blockers or cross-sex hormones, Genspect and other organisations working on evidence-based methods in the field of gender dysphoria, including the Clinical Advisory Network on Sex and Gender (https://can-sg.org/) and the Society for Evidence-Based Gender Medicine (https://segm.org/), are in a position to help design a better trial of gender interventions on children.

In the modest proposal which follows, I have set out potential criteria for an ethical puberty blocker trial. Your comments and suggestions would be very welcome, hopefully informing a viable alternative to the flawed NHS trial now beginning.

1. First do no harm, or at least don't do any more harm

One of the factors which would give pause to any critical-thinking person considering the NHS puberty blocker trial would be the prospect of new off-label drug prescriptions to children experiencing the psychological condition of gender dysphoria (Greek for 'bearing badly'). In a conventional trial for a new drug, for example blood pressure medication, we might expect risk of harm to be weighed against the possible benefits of the drug.

In the case of puberty blockers, the risks are well-known but the benefits cannot be taken for granted, because of the weakness of the evidential base in the original Dutch protocol. The University of York systematic review, cited by Dr Cass, found no evidence that puberty blockers improve outcomes for patients with gender dysphoria.

Appendix 9 of the Cass Review, ‘Learning points from the Gender Dysphoria Multi-Professional Review Group’ (MPRG) August 10th 2023, page 15, states it was “estimated that around 4,000 cases were being prepared by Tavistock GIDS for referral to the endocrine service.” Page 11 of this report also expressed concerns about GIDS patients obtaining puberty blockers from other sources, noting “Private providers do not follow the prescribing, administration and investigation/ monitoring protocols agreed and followed by the NHS.”

Based on these estimates, we can assume at least hundreds if not thousands of British children have already been prescribed GnRH agonists by the NHS and private or overseas clinics in answer to the psychological diagnosis of gender dysphoria. If those children are unwilling to desist from puberty blockers and may have already progressed to cross-sex hormones, they could be studied in an ethical puberty blocker trial without introducing further harm iatrogenically.

The reason why retrospective recruitment into a study is potentially useful in this case is that puberty blockers are a pathway to life-long treatment. Outcomes for the individual are not measured a matter of months, as in the example of blood pressure medication. To evaluate the effect of puberty blockers on the well-being of the adult, we might have to wait many years, particularly as there is evidence to suggest gender dysphoria could resolve spontaneously.

A reliable puberty blocker trial would be a longitudinal study comprising genetic tests for differences of sex development, health screening and psychological evaluation, rather than a short-term medical trial, if it is to provide meaningful results. An incidence of gender dysphoria which may diminish after short-term interventions should not be a significantly long period in the patient's whole life, we would hope.

It is not always necessary to manipulate a variable in real-time in order to construct a falsifiable hypothesis. As the available records suggest that only a minority of children who attended GIDS were put on the puberty blocker pathway by the NHS, there should be a control group available within the same cohort.

The MPRG report noted that other children seen by GIDS may have obtained private puberty blocker prescriptions, independently of obtaining a referral to NHS endocrinology or not. The latter group of children could form a subset of the test participants, in case of differences between NHS and private gender services.

Assuming the use of puberty blockers remains detectable after the fact, it should be possible to test a retrospective hypothesis such as "Children attending the GIDS clinic who used puberty blockers between 2014 and 2024 had better physical and mental health outcomes than children in the same cohort who did not use puberty blockers."

2. Use appropriate research methods for the intervention prescribed

Because gender dysphoria's justification for NHS treatment is a psychiatric condition listed in the DSM-5-TR (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision), it is questionable whether a medical model experimental design would be appropriate for evaluating the risks and benefits of puberty blockers.

If someone has high blood pressure an objective evaluation of their symptoms before, during and after a trial is possible. How the patient feels about having high blood pressure is not directly relevant to the efficacy of the drug used in a strictly medical trial, although psychological evaluation could be a useful secondary source of data.

The Children and Young People’s Gender Dysphoria Research Oversight Board refers on its website (https://www.england.nhs.uk/commissioning/spec-services/npc-crg/gender-dysphoria-clinical-programme/implementing-advice-from-the-cass-review/cyp-gender-dysphoria-research-oversight-board/) to “a range of validated tools, questionnaires and user feedback” which will be used in the NHS puberty blocker trial. This statement is vague, and does not indicate the use of any objective evaluation techniques.

To use self-report methods while providing the medical intervention of puberty blockers to treat the psychiatric condition of gender dysphoria is to confuse apples with oranges, and bananas. Those children who have already received puberty blockers in an attempt to resolve gender dysphoria should be fully evaluated for developmental and health side-effects of medical transition, not simply given a questionnaire about their feelings.

Some study subjects may be reluctant to admit that they or their parents have obtained 'gender affirming' drugs from unauthorised or overseas sources, potentially in breach of the current UK legislation. Patient loyalty to an unlicensed gender clinic or dark web drug dealer may be greater than the desire to provide accurate information to the study. Since we cannot be sure if self-reported use or non-use of puberty blockers and cross-sex hormones is accurate information, diagnostic tests might be devised to collect evidence of elective endocrine disruption. Those tests, if possible, could help eliminate a confounding variable from the study.

3. Find out what happened to all the transgender people

Another factor which could be considered in the design of an ethical puberty blocker trial would be the opportunity to correct the weaknesses of earlier studies in loss to follow-up. The authorities which have recorded new patient names without recording previous 'dead names', allowed alteration of birth certificates or assigned entirely new healthcare and social security numbers to transgender people have not helped research into the long-term effects of 'gender-affirming' treatments.

The current difficulty in following up studies previously attempted significantly weakens the ability to draw meaningful conclusions from earlier data. This should be rectified at the earliest opportunity with detective work to track down all those patients treated with puberty blockers and cross-sex hormones since the emergence of the 'Dutch protocol'. We might consider that those clinics have a duty of care to the patients they treated previously.

Collating data on former patients and their health outcomes should provide a baseline for the use of puberty blockers and their efficacy in resolving gender borne badly. Otherwise, we risk repeating harms that have already taken place to the cohort of puberty blocker recipients, girls and boys forgotten about when they aged into adult gender clinic services.

It seems absurd to propose a new set of puberty blocker experiments when data on outcomes for the previous cohort could not be collated, because it was being actively withheld by gender clinics. Using the principle of 'once bitten, twice shy', any clinician or manager who has withheld patient data from legitimate scrutiny should be automatically disqualified from participation in future studies.

4. Establish a psychosocial support cohort

If we are to truly disambiguate the benefits and harms of puberty blockers from other potential treatment options for gender dysphoria, we need a new control group going forward. It should not be difficult to identify a group of children and young people who have received puberty blockers with minimal psychosocial or psychological intervention, such as talking therapies, as that was the business model of GIDS and many other 'gender-affirming' clinics around the Western world.

What is currently missing is an identified control group of children who have received talking therapies only, without instant affirmation of cross-sex or genderqueer identity. Because the only NHS gender clinic for children became committed to a medical model for treating psychological distress, this should be no surprise. We have even less information on the children experiencing gender dysphoria who never attended GIDS.

A further disincentive to talking therapies for this cohort has been the institutional and personal intimidation of therapists by gender identity activists, including those activists with financial interests in the medical model. It should be clear that for any balanced trial of interventions for children with gender dysphoria to take place, this intimidation must stop.

Legal intimidation includes attempts to place restrictions on what a therapist may say to a patient in the privacy of a consulting room. Bans on 'conversion therapy' advocated for by the proponents of radical medical and surgical interventions on children are not only hypocrisy, they are psychological projection by those who would convert predominately gay and lesbian youth at the cost of health and fertility.

Conclusion

NHS plans to forge ahead with a new puberty blocker trial, despite the flaws highlighted by Genspect UK and others, represent a risk to the credibility of both national government and its public healthcare system. Should children be harmed by new prescriptions of puberty blockers, government ministers and NHS officials won't be able to say that they weren't warned. A clinical trial that doesn't acknowledge the mistakes of GIDS is a huge political, financial and legal liability, and the British public is not at all forgiving when children are harmed.

Critics of the 'Dutch protocol' for puberty suppression in gender non-conforming children have a limited window of opportunity to propose a better research design for the NHS and other healthcare providers around the world. I hope organisations and individuals can work together to offer viable, robust, and above all, ethical alternatives.

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Join the Discussion

Join us for a lively panel debate about puberty blockers with guest speakers Professor Michael Biggs, Dr Louise Irvine and psychologist and Tavistock whistleblower Sue Evans.

1. https://www.england.nhs.uk/commissioning/spec-services/npc-crg/gender-dysphoria-clinical-programme/implementing-advice-from-the-cass-review/cyp-gender-dysphoria-research-oversight-board/

2. https://segm.org/20-years-of-the-Dutch-Protocol-critical-analysis

3. https://www.bbc.co.uk/news/health-68549091