We’ve learned nothing about puberty blockers Gids clinicians have left a vacuum of data

For as long as puberty blockers were being offered as an off-label treatment by the NHS, clinicians were both ethically and duty bound to monitor their effectiveness. This fundamental duty was largely ignored by the clinicians at Gids who failed to collect adequate data, and rolled out the experimental treatment regardless. In a sign of just how far outside the bounds of normal clinical practice Gids was operating, one senior clinician appeared to be under the impression that auditing the outcomes of the experimental treatments they offered would actually be illegal.

As a result of their failings, we are left with a vacuum of data on the safety and effectiveness of puberty blockers and are back to square one when it comes to evaluating the medication as a prospective treatment for children with gender distress. It’s one thing to attempt to persuade an ethics committee to allow you to monitor the impact of a treatment already in use, albeit in an off-label capacity, quite another to convince them to give the go-ahead to experiment in children with a powerful treatment that will interfere with a critical stage of maturation. Following the withdrawal of off-label prescribing, anyone attempting to design an NHS trial to explore the efficacy of these drugs will need to convince an ethics committee of a sound rationale for reintroducing the drugs in the first place.

In most clinical trials, identifying the target or primary outcome of the treatment is the easy part: antibiotics reduce infection, epilepsy medications stop seizures, cancer treatments eliminate malignancy. No one needs a trial to prove that puberty blockers block puberty — the drugs are unequivocally effective in this regard. But puberty is neither a disease nor an illness. It is a vital stage in the transition from childhood to adulthood, marked by changes that extend far beyond the development of secondary sex characteristics. The brain undergoes extensive rewiring during puberty, creating the adult capacity for nuanced thought and complex decision-making, a process that isn’t complete until well into the third decade of life. Changes in the brain also allow sexual identity to develop. And elsewhere in the body, respiratory and circulatory systems undergo rapid growth and development. The skeletal system changes, increasing in bone density and musculature. Puberty blockers interfere with all of these processes in ways that may or may not be completely reversible — we can’t be sure, as many have not been studied.

But the importance of puberty as a critical developmental stage is such that any case to block it would need to be exceptionally strong to convince an ethics committee to green light a clinical trial. The bar will be set even higher, given the vulnerability of the target population: children who often present with multiple other psychiatric difficulties.

The rationale for using these drugs in gender clinics has undergone a highly unusual evolution over the past two decades. Initially prescribed to a very small number of boys to help them “pass” more easily as adult women, the drugs later began to be prescribed to the increasing number of adolescent girls presenting to these services. With the change in clinical caseload, the rationale for prescribing puberty blockers morphed into the notion that pausing puberty would give these distressed young people “time to think”. However, it is very clear from the data in the UK and Holland that the drugs did anything but, since more than 97% of children who took the puberty blockers went on to take cross-sex hormones. As Dr Anna Hutchinson, one of the original Gids whistleblowers, pointed out: “What are the chances that everyone given time to think, ends up thinking the same thing?”

As a neuropsychologist, the irony of stopping puberty in an effort to give young people time to think is not lost on me. Puberty is the neurodevelopmental process that literally constructs the neural architecture that allows people to think about complex and nuanced issues. Blocking puberty prevents the critical rewiring in the brain that underpins the ability make complex decisions. Puberty blockers may give children time to think but they simultaneously rob them of their developing capacity to do so.

In a pivot away from the “time to think” narrative, proponents currently argue that puberty blockers are vital to relieve the intense, even life-threatening psychological distress that trans and gender diverse people experience when puberty begins. This positions the treatment as a mental health intervention for acute psychological distress. Yet this distress may be anticipated rather than acute in those started on the medications as young as eight.

This is a world away from the original rationale. Chemically preventing a vital stage of maturation as a pre-emptive treatment for acute psychological distress also represents a major paradigm shift away from every other approach to treating psychological distress. This rationale is even more extraordinary given the evidence that puberty itself may be the best “cure” for gender related distress in many young people. The proportion of children diagnosed with gender identity disorder in childhood who persist into adulthood is contested, but most studies report that the majority (70% or more) no longer meet the diagnostic criteria once they have gone through natural puberty.

For a clinical trial to go ahead, an ethics committee must first be convinced of a solid rationale to override the safety concerns that were significant enough for the NHS to call a halt to off-label prescribing in this a highly vulnerable group. Researchers will also need to present a strong argument for trialling such an unprecedented treatment paradigm for psychological distress in young people.

If the researchers get this far, there is one final ethical barrier to overcome — and it is huge. The presence of detransitioners demonstrates that this medical pathway has the potential to cause significant, irreversible and lifelong harm. This is often minimised by gender clinicians as “treatment regret”, something which is common in many areas of medicine: many patients regret undergoing treatment when something has gone wrong with a procedure, or the results are not as they hoped. This is an inevitable part of all medical practice; results can never be guaranteed. However, detransitioners were given the wrong diagnosis and the wrong treatment for their distress. They represent the failure of the doctors treating them, not the failure of the treatment.

Even the fiercest advocates for puberty blockers acknowledge that there is no way of knowing who will or won’t be helped by medical transition. There is no middle ground; those who aren’t helped are harmed. Without a reliable clinical test to identify those who will benefit in the long run, an ethics committee that gives the go-ahead for a clinical trial does so in the knowledge that at least some of the children who take part will be unnecessarily put on a pathway of lifelong medicalisation with all its attendant risks and harms. Will any ethics committee in the land be persuaded that this is a price worth paying?

In the meantime, the new NHS gender services have a chance to right some of catastrophic wrongs of the original Gids service. Starting afresh, clinicians can ensure the careful record keeping and clinical audit that should be hard baked into every NHS service. Rigorous, standardised assessments and continuous monitoring of outcomes will provide much-needed information on the holistic treatments, including exploratory therapy that will be offered in the new services for young people with gender distress, since these, too, need to be evaluated.

If a puberty blocker trial ever gets past an ethics committee, we will face a further wait for the results. In the meantime, it is likely that vulnerable children will continue to seek these medications in the private sector, a place where puberty blockers have been  marketed anew as “necessary, safe, effective and life-saving” since the NHS announcement. At least parents now have a choice. When it comes to their children, they can believe the experts in the NHS who, having examined all of the evidence for both the safety and clinical effectiveness of puberty blockers, found it sufficiently lacking to withdraw the treatment. Or they can believe those who frame access to these drugs as a fundamental human right, while profiting financially from every prescription they issue. Rights do have a place in the treatment of children with gender distress: these children deserve the same evidence-based treatments as everyone else.

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Sallie Baxendale is a consultant clinical neuropsychologist and a professor of clinical neuropsychology at University College London.

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