03-07-2025
A landmark study of gender medicine is caught in an ethics row
ONE REASON that transgender medicine is such a fraught topic is that there is little evidence behind the arguments. When Hilary Cass, a British paediatrician, reviewed the field for an influential report published in 2024, she noted that most of the science underlying the prescription of puberty blockers and cross-sex hormones to teenagers (an approach called 'gender-affirming care") was 'remarkably weak".
One of her recommendations was that doctors and scientists should try to gather some better data. Britain's National Health Service (NHS) forbade the prescription of puberty blockers following Dr Cass's report, except as part of a clinical trial designed to explore whether they are genuinely beneficial. One such clinical trial, called PATHWAYS, is being led by researchers at King's College London. Originally scheduled for 2024, it is now supposed to begin later this year.
Running a clinical trial to settle the question might seem like a straightforward good idea. Its conclusions would be read around the world, as many countries are grappling with how best to regulate gender medicine. But a chorus of campaigners, including doctors' groups and parents' organisations, argue that the trial would be impractical, unethical and should not be allowed to go ahead.
As their name suggests, puberty blockers act on the brain to stop the release of sex hormones such as testosterone in males and oestrogen in females. When given to children with gender dysphoria, the drugs are supposed both to relieve psychological distress and buy patients 'time to think": to pause puberty while they consider if they want to go ahead with opposite-sex hormones (and possibly surgery) designed to make them more closely resemble the opposite sex. The trial plans to follow teenagers on puberty blockers for two years, with regular assessments of their 'physical, social and emotional health".
The trial has yet to receive ethical approval, and only bare-bones information about its design is available (King's College London told The Economist that it would not comment until the study had been approved). But even that is enough to worry critics. Some of the opposition comes from groups that are strongly in favour of gender-affirming care. The World Professional Association for Transgender Health, which writes guidelines for gender-affirming care, disagrees with Dr Cass on the lack of evidence for puberty blockers, and argues that it is unethical to limit them to participants in clinical trials.
Those doubtful of the merits of the gender-affirming approach are also sceptical. One frequently cited objection is that a clinical trial of puberty blockers seems hard to square with medical rules that require extra protections for trials involving children. David Bell, a psychiatrist and former board member of the Tavistock and Portman NHS Trust, which ran the biggest gender clinic in England and Wales until it was shut down in 2024, said in an article published in January that British law requires that trials minimise risks to a child's 'state of development"—something with which puberty blockers are specifically designed to interfere.
Many (though not all) doctors argue that, to be ethical, a clinical trial requires researchers to be in a state of 'equipoise": genuinely uncertain as to whether a treatment will be helpful or harmful. Louise Irvine, who helps run the Clinical Advisory Network on Sex and Gender, a group of medics who believe that gender-affirming care poses serious risks to patients, argues that what little evidence does exist for puberty blockers suggests they can cause harm. One study published in 2020, for instance, found significant decreases in bone-mineral density in children given puberty blockers. Reports from patients prescribed one such medication called Lupron for precocious puberty (in which puberty begins too early), rather than gender dysphoria, talk of serious problems with joints and skeletons in young adulthood.
Animal trials, meanwhile, suggest that blocking the production of sex hormones may hinder brain development in adolescence. One study in humans, again in children with precocious puberty rather than gender dysphoria, followed 25 female patients for three years and found an average decline in IQ of seven points. (Other studies have not found a detrimental effect.) And although puberty blockers are intended merely as a 'pause button", Dr Cass had concerns that children who take them almost always go on to further treatment. Data from the Tavistock suggest over 90% of children prescribed the drugs will go on to take cross-sex hormones—testosterone for females and oestrogen for males. If those are prescribed early enough in puberty, they can cause irreversible sterility.
The Tavistock data also suggest that the psychological effects of puberty blockers are hit-and-miss, with 34% of children seeing their mental health worsen and 29% seeing it improve. For Dr Irvine, all this is enough to tilt the balance away from equipoise—and thus from running the trial.
Others worry about the practicalities. The best clinical trials are blinded, in which neither doctors nor patients know who is receiving the treatment and who is not. But the effects of puberty blockers are dramatic enough to make blinding impossible. What's more, children with gender dysphoria have higher-than-normal rates of anxiety, depression and autism-spectrum disorders, all of which can muddy a trial's results. The Bayswater Support Group, an organisation for parents of gender-dysphoric children, argues that two years is too short a follow-up time for a treatment with lifelong effects.
Those practical worries can themselves shade into ethical problems, says Dr Irvine, who points out that, since all clinical trials expose patients to a risk of harm, they can be justified only if they add usefully to the sum of medical knowledge. 'If you've designed a bad trial that can't answer the question, it would be unethical to run it," she says.
Not everyone is opposed. Gordon Guyatt is an expert in evidence-based medicine at McMaster University in Ontario, Canada who has taken an interest in the subject. He argues that the possibility of producing useful data should weigh heavily on the ethical scales, even if the trial is imperfect. 'If it were to prove feasible it would be unethical not to do [a trial]," he says, 'because there is such polarisation, and the lack of high quality evidence is…making it hard to move forward."
There are options besides testing the drugs in humans. Stephanie Davies-Arai, who runs Transgender Trend, a campaigning group sceptical of gender-affirming care, thinks more animal studies should be done. Another idea is to make use of the fact that puberty blockers have been given to gender-dysphoric children for many years already. A 'data-linkage" study would look at the modern health records of those who had been given puberty blockers as teenagers, to see what had happened to them later in life. (A previous attempt to do just such a study was thwarted when British gender clinics refused to co-operate).
For now, the trial looks likely to go ahead. By the time a trial has been funded, says Dr Irvine, ethical approval is usually routine. But then again, few attract this much publicity and controversy.
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