Safety gap

The brittle reassurances of the puberty blocker boosters

Known unknowns

The rationale for a research project linked to Australia’s most influential gender clinic admits that “critical gaps” in the scientific understanding of puberty blockers “undermine their safe and effective use.”

This warning, as yet unreported in mainstream media, is at odds with widely publicised claims that puberty blockers—routinely prescribed off-label by Australia’s gender clinics to stop the normal sexual development of children as young as 9-13—are safe and beneficial, even “lifesaving.”¹

A fast and flawed 2024 “evidence check” by the Sax Institute—which Australia’s Health Minister Mark Butler told journalists he had read over the summer break—made the claim that puberty blockers are “safe and work well to delay puberty, and their effects can be reversed if stopped.”

This inspired an ABC News headline asserting that these drugs are “safe, effective and reversible.”²

Such reassurance is at odds with the international findings of multiple systematic reviews—the gold standard for being thorough and minimising bias when assessing the evidence for a health intervention—that the research data favouring this novel use of puberty blockers is very weak and uncertain, meaning one cannot be assured that children will be helped, not harmed.

And now an Australian grant application has come to light which candidly acknowledges the gap between the confident prescribing of puberty blockers for gender distress and the state of the evidence base.

The official description for the successful grant application also states that, “While the mental health benefits of these [puberty suppressing] hormonal interventions are evident, there remain critical knowledge gaps that undermine their safe and effective use.”

The rationale for the grant also notes that, “Increasing numbers of transgender adolescents are seeking specialist gender-affirming medical care.”

The $2.77m study was funded in 2023 by Australia’s National Health and Medical Research Council (NHMRC), the agency asked by Minister Butler to develop new national guidelines for the treatment of gender-distressed minors.

The study, entitled “Ensuring safe and effective puberty suppression for transgender adolescents,” has as its chief investigator Dr Ken Pang, who leads research at the gender clinic of the Royal Children’s Hospital (RCH) Melbourne, which pioneered this controversial hormonal treatment in Australia.

In a December 2023 news item from the Murdoch Children’s Research Institute (MCRI), which is the research partner of the RCH Melbourne gender clinic, Dr Pang said one aim of the new NHMRC-funded study was to determine whether puberty blocker treatment “has any impact on cognitive development so young people and their families can make the best possible decisions.”

The adolescent brain is not fully matured until around the age of 25.

RCH and MCRI did not reply to GCN’s questions about the implications of the safety deficit—acknowledged in the 2023 grant—for clinical practice and informed consent at the gender clinic.

In December, Wes Streeting, the Health Secretary of the UK’s centre-left Labour government, imposed an indefinite ban on private prescribing of puberty blockers for gender distress.

In the House of Commons, Mr Streeting said it was “a scandal that medicine was given to vulnerable young children, without proof that it was safe or effective, or that it had gone through the rigorous safeguards of a clinical trial.”

An end to routine use of puberty blockers in the public NHS had already been announced following England’s 2020-24 Cass review which noted the “remarkably weak evidence” for treatment of gender dysphoria.

In the wake of the Cass review, a group of UK researchers led by child and adolescent psychiatrist Professor Emily Simonoff of King’s College London and paediatric neurodisability consultant Dr Michael Absoud has been awarded a £10,694,900 grant for clinical trials and studies of puberty blocker use with gender-distressed minors—GCN

The summary for the 2024-31 grant says: “The idea was that GnRHa [puberty blockers] might give young people time to think about their identity without worrying about their bodies changing during puberty.

“However, we don’t know if GnRHa are safe and helpful for young people with gender incongruence. We also do not know enough about how identity and feelings develop for young people with gender incongruence as they grow up and what treatment is helpful.”

One line of inquiry for the researchers will be “whether using GnRHa affects young people’s thinking (cognition) and brain development… Young people’s learning will be measured with ‘paper and pencil’ tests/activities several times to chart how these change. Physical brain development will be studied at the same time with brain scans.”

Stop and think

Australia’s state of Queensland, governed by the centre-right Liberal National Party, has paused any further use of hormonal treatment for gender-distressed minors in the public health system, pending an independent review of the evidence.

Like its interstate counterparts, the Queensland Children’s Gender Service follows the “Australian standards of care document and treatment guidelines” issued by RCH Melbourne in 2018, with Dr Pang among that document’s authors.

Puberty blockers, used to suppress the natural sex hormones of a normally timed puberty, are prescribed for children who feel distress in their birth sex and identify as transgender or non-binary.

In 2015, the then RCH gender clinic director, paediatrican Dr Michelle Telfer, told the readers of GQ men’s magazine that puberty blockers “don’t stop growth generally, or your brain from maturing emotionally and cognitively, they just stop the sexual characteristics from developing.”

It is unclear whether adolescents need their natural sex hormones during puberty to take advantage of a “critical window” for cognitive development. If there is such a time-sensitive window, then a patient who stops puberty suppression might not be able to catch up in cognitive development, notwithstanding the (belated) return of sex hormones.

The RCH Melbourne treatment guidelines make the confident claim that puberty suppression “is reversible in its effects.”

That guideline document, now badged as the 2023 Version 1.4, still makes the claim that patients on puberty suppression are “given time to develop emotionally and cognitively prior to making decisions on gender-affirming hormone use which [has] some irreversible effects.”³

In a 2024 review of the scientific literature, British neuropsychologist Professor Sallie Baxendale concluded that, “There is no evidence that cognitive effects are fully reversible following discontinuation of [puberty blocker] treatment.”

The RCH Melbourne treatment guidelines, celebrated last month as “excellent” by Australia’s Assistant Health Minister Ged Kearney, have not been updated to reflect the acknowledgement by RCH and MCRI that the effects of puberty blockers on the still developing adolescent brain are unknown.⁴

However, towards the end of last year, the RCH gender clinic quietly abandoned the long-standing claim on its website that puberty blockers “are reversible in their effects,” substituting without announcement the claim that blockers “are largely reversible.” In what way they might be irreversible is not explained.⁵

In August last year, Dr Pang was co-author of an article in The Conversation which cherry picked studies favouring the use of puberty blockers but did concede that “it remains unclear what effect puberty blockers may have on cognitive development.”

On ABC Radio last month, Jeremy Wiggins, the chief executive of the trans rights lobby Transcend Australia, which works closely with the RCH gender clinic, claimed that puberty blockers are “a hundred percent reversible.”

Mr Wiggins said there was “so much disinformation out there,” and recommended Transcend’s “evidence-based fact sheets.”

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Video: Uncomfortable truths, a documentary from Travis Brown, content producer for Genspect

A US study is under way focusing on “the impact of pubertal suppression on adolescent neural and mental health trajectories.” The $US 3 million study, funded by the Department of Health and Human Services, involves 132 “transgender adolescents” at three children’s hospitals, with half of them on puberty blockers and the other half untreated.

"The rationale for the study is that whatever mental health benefits it confers, pubertal suppression “may also disrupt puberty-signalled neural maturation in ways that can undermine mental health gains over time and impact quality of life in other ways.”

“The overall impacts of [puberty blocker] treatment have not been systematically studied. In order to probe these effects, this project focuses on the assessment of dimensional mental health and three neural systems … cognitive/emotional control, social cognition, and reward responsiveness.

“Existing literature documents marked maturation in these systems during normative adolescent development, and gonadal [sex] hormones are thought to contribute to this maturation.” Begun in 2021, the study is to finish next year—GCN

Trans20

The better-known research project at the RCH gender clinic is the Trans20 longitudinal study of minors given hormonal treatment, which began recruiting participants in 2017.

The implications of Dr Pang’s 2023 “safe puberty suppression” project for Trans20 are unclear.⁶

A 2019 protocol paper describing the Trans20 study acknowledged “a need for more empirical data to inform best practice in important areas such as risk and protective factors and the long-term safety and outcomes of medical interventions.”

The protocol makes no mention of the cognitive uncertainty of puberty blockers.

It does disclose “an urgent need for more evidence to ensure optimal medical and psychosocial interventions.”

Last year, an open letter signed by 31 medical practitioners called on RCH and its research partner MCRI to release key results from Trans20.

“With 4-7 years of data now collected, we believe it’s time for the Royal Children’s Hospital to publish their preliminary outcome findings,” the letter said.

GCN sought comment from the RCH, MCRI, Dr Pang and the Sax Institute. GCN acknowledges that gender-affirming clinicians believe their interventions help vulnerable young people.

1. Puberty blockers are licensed for medical conditions such as central precocious puberty and hormone-fed cancers but not for the psychological distress of gender dysphoria. England’s 2020-24 Cass review warns against the practice of citing the relative safety of pubertal suppression for precocious puberty as if this can be generalised to the quite different intervention of halting a normally timed puberty. One of the concerns about transgender puberty blocking is its potential effect on identity development, including sexual orientation.

2. The Sax Institute promotes its evidence check method as “a fast and accurate summary” of the scientific literature. In its review for New South Wales Health, Sax departed from the evidence-ranking system of the NHMRC, with the effect that the quality of some studies was exaggerated. The fact that puberty blockers “work well to delay puberty” is unsurprising; the key issue is the lack of any good evidence that these drugs are “effective” in producing the mental health benefits claimed by gender clinicians.

3. International data suggests that almost all the children begun on puberty blockers will go on to cross-sex hormones, which are meant to be taken lifelong. This undermines the “time to think” rationale for puberty suppression.

4. Mr Butler said he had asked the NHMRC to undertake a “comprehensive review” of the RCH Melbourne guidelines. Ms Kearney characterised the NHMRC project as merely an “update” of the RCH guidelines at the behest of the gender medicine lobby, the Australian Professional Association for Trans Health (AusPATH). Dr Pang, one of the authors of the RCH guideline, has declared his voluntary membership of the AusPATH research committee as a potential conflict of interest.

5. Archived web pages—and the sharp eye of a contact—revealed the shift in the RCH position on puberty blockers.

6. In 2021, Dr Pang was awarded a $1.57 million NHMRC grant for Trans20 with the promise that this research “will address critical knowledge gaps in this important and emerging area of healthcare so as to maximise health outcomes and minimise harm for this vulnerable group [of trans-identifying minors].”