Unfinished business
Psychiatrists call for urgent tracing of Tavistock youth as the puberty blocker trial stalls
A group of 23 consultant psychiatrists has urged the UK government to pursue a follow-up study of the 9,000 minors seen at the London-based Tavistock gender clinic rather than persisting with the contentious clinical trial of puberty blockers.
“There will be a lot we can learn from this cohort [of ex-Tavistock patients] and this should now be the priority,” the psychiatrists wrote in a letter to The Times newspaper on Monday.
“It was alarming to learn that National Health Service adult clinics refused to co-operate with the research team who were tasked with this follow-up study, and we would hope that a reinvigorated effort would now be undertaken.”
On Friday, it was announced that the PATHWAYS clinical trial of puberty blockers, which was to start recruitment of up to 250 participants as young as age 10, had been put on hold after the Medicines and Healthcare products Regulatory Agency (MHRA) raised safety and ethical concerns.
Those concerns included the risk of “long-term biological harms” including sterilisation, permanent bone damage, and cognitive ill effects. In talks begun this week with the trial researchers, the MHRA is seeking a series of changes and restrictions, most notably a minimum age of 14 for participants.
Detransitioner Keira Bell, who is involved in potential High Court litigation to stop the clinical trial, said evidence of the harm done by blockers to former Tavistock patients such as herself was available.
“They can find all of my medical notes & tests, which I also have in my possession, to add to the list of children already put on [blockers] who suffered negative effects,” she tweeted on Sunday.
She recalled feeling her body “shut down” on puberty suppression, with night sweats, difficulty sleeping and studying at school.
The “data linkage” follow-up study to discover the adult clinic outcomes of ex-Tavistock patients had ethical clearance and, like the clinical trial, was recommended by paediatrician Hilary Cass following her four-year review of youth gender dysphoria treatment. It’s thought that some 2,000 of the 9,000 minors seen at the Tavistock between 2009 and 2020 were prescribed puberty blockers.
On hold: Helen Joyce of the group Sex Matters discusses the pause to the trial
Nothing new here
The Department of Health and Social Care described the MHRA’s concerns as “new” and said the trial would be paused pending “scientific dialogue” with the researchers in charge at King’s College London.
In a statement to parliament, Labour Health Secretary Wes Streeting said the trial “will not start to recruit until the issues the MHRA raised have been resolved. It will only be allowed to go ahead if the expert scientific and clinical evidence and advice conclude it is safe to do so.”
Several commentators have pointed out there is in fact nothing new about the reasons given for halting the trial, prompting the question how the research secured regulatory and ethical approval last November.
Journalist Hannah Barnes, known for her investigative work on the scandal at the Tavistock clinic, noted that the MHRA had belatedly acknowledged the implications of the reality that the vast majority of children begun on blockers would proceed to cross-sex hormones.
Early puberty suppression followed by cross-sex hormones is expected to cause sterilisation. The trial was to recruit children from Tanner Stage 2, the onset of puberty occurring around age 10. But delaying blockers until age 14 means participants, especially females, may be well advanced in puberty.
“Blocking early puberty, the MHRA says, risks sterilising children and is unethical,” Barnes wrote in The Times.
“But what remains [with a minimum age of 14] is a trial purporting to analyse the effectiveness of blocking puberty to treat gender-related distress which only studies participants who have already gone through puberty (at least for girls).
“It is highly questionable whether such a study could tell us anything useful—and therefore might also be unethical. It would be loathed by those who support the medical transitioning of children, too.”
The original protocol for the trial also faced the objection that its poor design meant it could not fill the gaps in evidence lamented by Dr Cass.
Under the protocol, the two-year trial is to recruit minors with a diagnosis of gender incongruence—a depathologised variant of gender dysphoria without any necessary distress. The randomisation of the trial involves merely a difference in timing of the same treatment, with one group starting on blockers straight away and the other beginning after a year’s delay. The outcome measure is a self-reported quality-of-life survey.
One key change proposed by the MHRA is a “much more detailed physiological safety assessment”, given that “the physiological and adverse pharmacological impacts may long outlast and outweigh any detected differences [in subjective quality of life].”
The MHRA also urges greater vigilance for the possibility that suppression of natural sex hormones interferes with development of the adolescent brain.
“We recommend that advice from independent clinical experts in neurocognition and brain imaging should be sought to advise what degree of adverse fMRI signal change between [brain] scans would necessitate withdrawal from the study. We would like to discuss this as a key safety assessment measure at 12 months.”
Puberty blockers are prescribed “off label” by gender clinics, meaning they do not have regulatory approval for use with gender dysphoria or incongruence. Blockers, known as gonadotropin-releasing hormone analogues (GnRHa), overstimulate the pituitary gland until production of the male and female sex hormones required for normal development is suppressed.
GnRHa drugs have been tested and licensed for conditions including prostate cancer, where testosterone can feed tumour growth, and central precocious puberty, when premature sexual development begins in very young children and the hormone suppression drugs are administered until they are old enough to enter puberty in sync with their peers.
Explainer: how do GnRH drugs work?
See you in court
The litigation brought by detransitioner Bell, together with parents’ organisation Bayswater Support Group and psychotherapist James Esses, seeks judicial review of the decisions last November to approval the trial by the MHRA and a research ethics committee (REC). The defendants are listed as the co-ordinating Health Research Authority and Health Secretary Streeting.
“Both decisions were flawed on the basis of irrationally approving a clinical trial on a group that is vulnerable not only because of their age, as children below the age of 16 who may potentially be as young as 10 … but also their vulnerability from a high incidence of other conditions such as autism and ADHD, and social difficulties,” says the statement of facts and grounds for the judicial review application.
“The trial design is inherently flawed; it lacks a rational scientific purpose; and it is incapable of yielding clinically meaningful data.”
The judicial review application, which is yet to go to a hearing, relies in part on expert evidence from neuropsychologist Sallie Baxendale of University College London, the author of a 2024 review paper warning that blockers may interfere with critical windows in development of the adolescent brain.
“Professor Baxendale explains that the trial involves exposing children to an intervention that deliberately interferes with normal development, in the absence of a clear scientific rationale, a testable hypothesis, reliable outcome measures, or any evidence-based method of identifying who is likely to benefit and who is likely to be harmed. Decisions about enrolment [in the trial] are therefore necessarily based on belief rather than evidence,” the statement says.
The judicial review claim also cites the work of Glasgow University’s Professor of Integrative Physiology, Neil Evans, who with Norwegian researchers has demonstrated enduring cognitive impairment in sheep given GnRHa puberty blocker drugs. The implication is that as fellow mammals, humans might suffer similar deficits in thinking and memory.
“There was obviously relevant information [that Professor Evans] could have provided to the MHRA or REC had he been asked, which would have been highly relevant to their decision-making,” the statement says. “Yet no questions appear to have been asked about this issue…”
The statement says the REC appeared to have been misled by the claim of the King’s College researchers proposing the trial that “there was no data at present on the cognitive impacts of puberty blockers”.
Children in the trial were to be promised up to £500 in Love2Shop vouchers for completing psychometric tests which could be redeemed at shops including Currys, Uber Eats and Xbox, according to The Daily Telegraph.
Dr Cass contends that the question of the safety and effectiveness of puberty blockers for gender-questioning minors is one that must be answered.
“These children who are on this trial will be about the most closely monitored you could imagine,” she told the BBC before the MHRA’s February 20 intervention.
“People will be very carefully looking at all aspects—their cognitive development, their psychological development, their bone development—and any hint that there are any significant long-term risks, they would come off the trial.
“So, it’s a very careful trial, but what’s much more worrying is the children outside the trial who are getting these drugs from unregulated and dangerous sources [online, for example] with no monitoring, and possibly for the wrong reasons.
“If we never answer this question [of the evidence for puberty blockers], we’re going to have ongoing charlatans just handing out inappropriate drugs.”
On Sunday, Dr Cass criticised the MHRA-imposed pause in the trial.
“There are no new research findings and the MHRA hasn’t presented any new evidence,” she told The Observer. “It feels to me like they are responding to political pressure rather than to science.”
Conservative Opposition Leader Kemi Badenoch welcomed news that the puberty blocker trial had been paused.
“We know that these drugs are actually a form of conversion therapy on gay kids told they were born the wrong sex,” she tweeted.
“Let’s focus on giving children and young people a positive body image instead of drugging them into oblivion and leading them down the path of irreversible biological changes.
“No child can consent to such treatments. So, it is right that this unethical trial is paused. It should be stopped completely.”
The UK’s Prime Minister Keir Starmer has come under cross-party pressure, including from within his own Labour Party, over the trial as an unacceptable experiment on vulnerable children.
Students at King’s College London have launched a petition and open letter opposing the trial, the premise of which they describe as “ideologically based”.
“[The trial] treats claims associated with gender identity ideology, such as the notion that a child’s asserted gender identity should be affirmed through medical intervention, as established fact, rather than as hypotheses that remain subject to serious debate within medicine, psychology, and the social sciences,” the open letter says.
“When a trial embeds a particular ideological framework as its starting point, it risks shaping research questions, outcome measures, and interpretation of results in a way that favours a predetermined conclusion. Such bias is especially concerning in a field where the evidence base is weak, the population is vulnerable, and alternative explanatory and therapeutic models exist.”