Guidelines in the balance
Can evidence-based medicine survive gender-affirming treatment?
Opinion | Australia has been promised interim advice on puberty blockers by the middle of 2026. Are these drugs effective for gender distress? Is it safe to suppress the natural puberty of teenagers?
Will this new treatment advice mirror the UK, which has prohibited routine use of blockers for gender-distressed minors, or Germany, which recently issued a “gender-affirming” guideline encouraging such medicalisation?1
Australia’s federal Health Minister Mark Butler had the UK in mind when he sought urgent advice on the safety of blockers from his health bureaucrats, according to documents obtained under Freedom of Information law. This fact is not well known.
Mr Butler, from the centre-left Labor party, asked for this advice on 13 December 2024—one day after news that his UK Labour counterpart, the then Health Secretary Wes Streeting, had imposed an indefinite ban on routine prescription of blockers following the 2020-2024 Review of gender dysphoria care led by the distinguished paediatrician Dr Hilary Cass.
In the House of Commons, Mr Streeting said: “The Cass Review made it clear that there is not enough evidence about the long-term effects of using puberty blockers to treat gender incongruence to know whether they are safe or beneficial.”
“That evidence should have been established before they were ever prescribed for that purpose. It is 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.”
The cautious UK position is based on “gold standard” systematic reviews of the evidence base for youth gender dysphoria. Such reproducible reviews—independently commissioned in countries including the UK, Sweden and Finland since 2018—have found the evidence for blockers and hormones to be very weak and uncertain. In other words, gender clinicians have no firm basis for recommending this hormonal treatment as beneficial for minors with gender distress. And these drugs come with known and unknown risks of harm.
In Germany, however, the guideline development group of clinicians decided not to persist with a full systematic review assessing the quality of the evidence for treatment. They would have been acutely aware that such an assessment would weaken any advice recommending blockers and hormones for minors.
And so, the German guideline was downgraded. It was not to be evidence-based after all, but consensus-based, meaning merely the opinion of some selection of experts. The gender-affirming members of the guideline group, already in favour of these hormonal treatments, agreed with one another. Two members worried about the poor evidence—prominent psychiatrists and researchers Dr Alexander Korte and Professor Florian Zepf—resigned from the guideline group in protest.2
The German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN) registered a detailed dissent from the guideline. “[T]he question is raised ‘How should the right to self-determination and the underlying ethical principle of promoting autonomy be weighed against the protection of minors from treatment decisions that extend far into their future and have potentially fatal consequences?’ One searches in vain [through the guideline] for answers to such and many other relevant medical-ethical questions…”3
Yes, Minister
In January 2025, Australia’s Minister Butler announced that the National Health and Medical Research Council (NHMRC) would develop new national treatment standards and undertake “a comprehensive review” of the current, de facto national guidelines. The latter, first issued in 2018 by the gender clinic of the Royal Children’s Hospital (RCH) Melbourne, have been misleadingly promoted as “Australian Standards of Care and Treatment Guidelines for Trans and Gender-Diverse Children and Adolescents”.
Like the RCH Melbourne guidelines, Mr Butler used language unhelpful for an open-minded inquiry into the unprecedented spike of minors seeking hormonal treatment. The minister’s statement was headlined, “Health care for trans and gender-diverse children and adolescents [Emphasis added]”. As Dr Cass emphasised, there are many potential pathways into and out of gender distress, and a minor’s declaration of a trans identity should not foreclose ethical consideration of underlying causes or non-invasive treatment alternatives. Consistent with the minister’s narrow, identity-politics framing of the task at hand, the NHMRC says it is developing “National clinical practice guidelines for the care of trans and gender-diverse people under 18 with gender dysphoria [Emphasis added]”.4
However, Minister Butler’s announcement did have reassuring elements. He stressed that “vulnerable” young people were entitled to “the best medical advice and care available”. The new guidelines, he said, would be developed in accord with NHMRC standards and the international GRADE system for rating the quality of the evidence said to favour treatment advice.
Those NHMRC standards require “well-conducted systematic reviews” of the evidence base. Every credible systematic review since 2018 has confirmed the poverty of the evidence base relied on by paediatric gender clinics.5 At a media conference in January 2025, Butler said the NHMRC had described the gender dysphoria field as “contested and evolving”.
Surely, therefore, the NHMRC project is bad news for the gender medicine lobby? Yet the Australian Professional Association for Trans Health (AusPATH) has stated its opinion that the NHMRC is “best placed” to review the RCH Melbourne guidelines, which AusPATH itself had fulsomely endorsed as if they were rigorous national standards.
In January 2025, Butler’s then deputy minister, Ged Kearney, put a rather different spin on the job assigned to the NHMRC. Ms Kearney said it was not a “national inquiry”—the great fear of gender clinicians—but simply an update of the “excellent” current guidelines. And this update, she said, had been requested by AusPATH and the lobby group Transcend, both of which would be consulted by the NHMRC.
She made no reference to any input by Genspect or the Society for Evidence-based Gender Medicine, both of which are critical of the risk-to-benefit profile of gender medicalisation for minors.
What explains the muted response of trans activists to an NHMRC project which will potentially confirm the lack of rigour in the RCH Melbourne guidelines—the very document that entrenched the gender-affirming treatment model in Australia without any firm foundation in scientific evidence? Should gender clinicians in our children’s hospitals steel themselves for NHMRC-endorsed guidelines that apply the GRADE system, confirming the evidence for their treatment regimen of blockers and hormones to be of “low” or “very low” certainty?6
The chosen
The key body driving the new NHMRC standards is the Gender Guidelines Development Committee. Part of its role is “prioritising topics and questions for a systematic evidence review”. This committee is to develop draft guidelines for public consultation, consider the feedback and put a final draft to the NHMRC Council, with the chief executive officer to issue the complete, approved guidelines in 2028.
What should this guideline development committee look like? It should “[b]e composed of an appropriate mix of expertise and experience, including relevant end users”, according to NHMRC standards.
Of the 18 members of this committee, four were appointed because of their “lived experience of accessing gender services”. There is also a Gender Guidelines Reference Panel “to provide a diversity of perspectives on topics and priorities relevant to the end users of the guideline”. However, this reference panel does not have decision-making authority.
“Lived experience” can be a mask for gender-affirming groupthink. I asked the NHMRC if the Gender Guidelines Development Committee, the key decision-maker, included anyone who had desisted, detransitioned or decided that puberty blockers or cross-sex hormones were not necessarily the right response to gender distress.
The NHMRC’s answer blurred process with outcome, and the key guideline development committee with the less consequential reference panel: “NHMRC engaged directly with individuals with a variety of personal experiences of seeking gender services while under 18 in Australia, including those who have continued, paused, or discontinued aspects of their care, as well as their parents and carers. There is a range of experiences amongst the lived experience members of the Gender Guidelines Development Committee and the Reference Panel.”
Were those with lived experience contrary to the claims of the gender-affirming model, confined to the reference panel?
What about the balance of expert appointees? Of those 14 committee members, there is not a single clinician or researcher known to be sceptical of the gender-affirming model.
There is no counterbalance to Dr Ken Pang. On the NHMRC guideline webpage, he is described as a “Consultant paediatrician and research lead at the Department of Adolescent Medicine, Royal Children’s Hospital Melbourne [and a] Senior Principal Research Fellow and Transgender Health Research Group Leader, Murdoch Children’s Research Institute”.
No mention of the RCH Melbourne gender clinic, Australia’s most influential.
If you go to that clinic’s website, you will see Dr Pang’s photo with the following description: “Ken joined the Gender Service in December 2015, and brings to the role a strong clinical focus on child and adolescent mental health and extensive research experience. Ken is excited to assist and learn from children, adolescents and families dealing with gender issues, and is leading the service’s research efforts…”
The RCH gender-affirming clinic and its de facto national treatment guidelines are at the dead centre of a highly contested debate about the ethics and evidence for puberty blockers, cross-sex hormones and trans surgery offered to minors.
On the NHMRC guideline webpage, Dr Pang’s profile lists 14 potential conflicts of interest, including co-authorship of the RCH Melbourne guidelines; multiple grants from the Medical Research Future Fund, the NHMRC, and RCH Melbourne; receipt of an NHMRC Leadership Fellow award; and membership of gender-affirming lobby groups, both the World Professional Association for Transgender Health (WPATH) and AusPATH.7
True, Dr Pang is just one among 14 experts on the guideline development committee, but it is reasonable to suppose he will have an outsized influence as a subject matter specialist. And the committee will, in effect, have to evaluate the record of Dr Pang, the RCH Melbourne clinic and its sub-standard treatment guidelines.
Tipping the balance?
I asked the NHMRC if it believed the guideline development committee was balanced. A spokeswoman said: “NHMRC recognises the importance of incorporating a diversity of perspectives and experiences as part of a robust guideline development process.”
“Members were not selected based on their personal views but for their expertise, experience, and ability to contribute to rigorous, evidence-based decision-making. Including a wide range of expertise also helps to minimise the risk of any one member’s bias or influence.
“As part of NHMRC’s commitment to transparency, disclosures for committee members have been made available on the website and will continue to be updated should new disclosures arise throughout the process.”
Recall that Minister Butler gave the NHMRC two jobs: to review the RCH Melbourne guidelines and to develop new, truly national guidelines. I searched the NHMRC gender guideline webpages but couldn’t find any reference to the RCH review.
Was the “comprehensive review” going ahead?
“A review of the [RCH] Australian Standards of Care and Treatment Guidelines for Trans and Gender-Diverse Children and Adolescents will form part of a review of existing guidelines and evidence that will inform the new guidelines,” the NHMRC spokeswoman said.
A missing review
How are Dr Pang’s multiple conflicts of interest to be managed? What does his record show about the tension between the gender-affirming worldview and evidence-based medicine?
The RCH Melbourne treatment guidelines, with Dr Pang as a co-author, cite no systematic review of the evidence base; such a review is a necessary foundation for a trustworthy guideline.
And yet Dr Pang was among the researchers who ran a pioneering 2018 systematic review of hormonal treatment for gender-distressed adolescents, undertaken with money from the RCH Foundation. Was this review intended to be part of the guideline development process at the RCH gender clinic—until its disappointing results proved inconvenient?
The review appeared in a leading journal, Pediatrics, and was promoted as the “first systematic review” of its kind. Its conclusion: “Low-quality evidence suggests that hormonal treatments for transgender adolescents can achieve their intended physical effects, but evidence regarding their psychosocial and cognitive impact [is] generally lacking [Emphasis added].”
There are serious questions about how the arguably experimental gender-affirming model became routine treatment at RCH Melbourne and thereafter the de facto national standard in Australia for responding to gender-distressed minors.
In 2019, Dr Pang was co-author of a planning paper for a longitudinal study of RCH gender clinic patients. That paper declared “an urgent need for more evidence to ensure optimal medical and psychosocial interventions” with this group of gender-distressed minors.
In 2022, the RCH gender clinic stated that the effect of puberty blockers on the still-developing adolescent brain was unknown. This was not a public acknowledgement; it was confined to a clinic newsletter for patients and families.
Although the RCH treatment guideline is badged as Version 1.5, suggesting updates have kept it up to date, it still claims puberty blockers to be a “reversible” treatment that allows children “time to develop emotionally and cognitively” before embarking on lifelong cross-sex hormones. No mention of the possibility that blockers interfere with critical windows in adolescent cognitive development. (In late 2024, the webpage of the RCH clinic abandoned its previous, confident claim that puberty blockers were “reversible” in their effects. This was changed to “largely reversible” without explanation or further detail.)
This knowledge gap about blockers and the brain has been on the public record for some time. In October 2019, I reported that Dr Pang had advertised a PhD project with the pitch that puberty blocking typically lasts “several years, and provides an opportunity to learn how the teenage brain develops in the absence of sex hormones [which are suppressed by puberty blockers].”
In April 2025, Family Court judge Andrew Strum highlighted evidence that RCH “has only recently employed a PhD candidate to study possible effects [on the brain] despite blocking children’s puberty for several years”. Justice Strum made orders that “Devin”, a 12-year-old gender non-conforming boy, be protected from proposed puberty blocking at the RCH gender clinic.
Cass controversy
And yet, when later researchers—for example, the University of York authors commissioned by Dr Cass—followed Dr Pang in applying systematic reviews to the field of paediatric gender medicine, he rallied to the defence of the evidence base he had found threadbare just a few years beforehand.
He has put his name to gender-affirming polemics against Dr Cass’s 2024 report, which found the evidence for blockers and hormones to be “remarkably weak”. Dr Pang should have been the last person to be surprised by such a finding, given his publications from 2018-19.
In a 2024 amicus brief for America’s landmark Skrmetti case, which involved a challenge to a state ban on paediatric medical transition, Dr Pang and other gender clinicians claimed that the University of York’s systematic reviews, critical to Dr Cass’s conclusions, were “unreliable, inter alia, because they arbitrarily exclude much of the evidence showing that gender-affirming medications are safe and effective treatments for gender dysphoria. Indeed, researchers have found that the York [systematic reviews] inappropriately exclude nearly half of studies on puberty blockers and more than a third of studies on cross-sex hormone treatments.”
“The Cass Review commits another fundamental error by holding this area of medicine to an evidentiary standard that is not required or typical in pediatrics.”
Dr Cass has rejected this claim as misinformation. “There has been the question of ‘Have we set a higher bar for this systematic review [of paediatric gender medicine]?’ And we absolutely haven’t,” she told Scotland’s parliament. “These young people should get the same standard of evidence in their care as every other young person.”
As for supposedly arbitrary exclusion of evidence, the Cass criterion was the quality of the research. Low-quality studies with a high risk of bias were excluded from the synthesis. It’s true there were very few high-quality studies in the field but, as Dr Cass told the BBC, there were “quite a number of studies that were considered to be moderate quality, and those were all included in the analysis. So nearly 60 per cent of the studies were actually included in what’s called the synthesis.”
In an interview with The New York Times, Dr Cass said: “I can’t think of any other situation where we give life-altering treatments and don’t have enough understanding about what’s happening to those young people in adulthood.”
Speaking to the BBC, she said: “Adults who deliberately spread misinformation about this topic are putting young people at risk, and in my view that is unforgivable.” She did not dispute that some patients appeared to have benefitted from blockers and hormones. “But what we need to understand is what’s happening to the majority of people who’ve been through these treatments, and we just don’t have that data,” Dr Cass said.
“I certainly wouldn’t want to embark on a treatment where somebody couldn’t tell me with any accuracy what percentage chance there was of it being successful, and what the possibilities were of harms or side effects.”
It’s worth keeping in mind that Dr Cass also commissioned a peer-reviewed evaluation of treatment guidelines, including the RCH Melbourne document authored by Dr Pang and his gender clinic colleagues. The RCH guideline was rated 19/100 for the rigour of its development, 14/100 for editorial independence, and judged not fit for use.
Medical politics
Dr Pang was also a co-author of the so-called Yale white paper critique of the Cass Review. Its complaint was partly political. “In the short time since its release, the [Cass] Review has been used to justify restrictions on healthcare for transgender youth [in Republican-run US states]. In March 2024, [England’s National Health Service] announced that it would deny puberty-pausing medications to those under age 18 outside of a research setting,” the 2024 white paper says.
And, again, the gender-affirming focus is on the sheer number of studies favouring hormonal treatment, not their inconveniently poor quality, as if clinicians could go forth and recommend these medical interventions more confidently when there are 100 badly designed studies, as opposed to 10 badly designed studies.
“Amongst our author group, we have 86 years of experience in caring for more than 4,800 transgender youth and have published 278 peer-reviewed studies, 168 of which are in the field of gender-affirming care. The holistic care that the clinicians among us provide is rooted in decades of research; it is not controversial in the world-class pediatric health centers where we practice,” the white paper says.
This white paper was not peer reviewed and although it involved two Yale academics (one of them a lawyer), it lacks the university’s imprimatur. It does not appear on the NHMRC webpage listing Dr Pang’s declaration of interests. The Yale white paper itself has been critiqued in a peer-reviewed article published in 2025 and co-authored by a veteran psychiatrist in the gender dysphoria field, Professor Steven B Levine.
Which Dr Pang has been appointed to the NHMRC guideline development committee? The version who was one of the first to run a systematic review and acknowledge the lack of good evidence for the medical transition of minors, or the version who has more recently talked up the strength of the evidence in a political context?
The NHMRC did not directly answer GCN’s question about how it would handle the conflict of interest created by Dr Pang’s role as co-author of the RCH treatment guidelines.
But the spokeswoman said: “NHMRC has a range of conflict-of-interest management strategies in place for meetings and discussions regarding the evidence, including review and consideration of declarations of interest at each meeting. Management strategies will be determined where required, in line with best practice in guideline development.”
“Being affiliated with certain organisations did not automatically preclude appointments, however types of positions, such as board membership, constituted a higher risk of bias.
“Declarations of interest from potential candidates of the Gender Guidelines Development Committee were assessed by the Gender Guidelines Governance Committee using an established risk rating matrix.”
What, then, is the purpose of the governance committee? The NHMRC webpage says this committee was “established to provide advice on the composition of the Gender Guidelines Development Committee, including reviewing disclosure of interest declarations of prospective members, and to advise NHMRC on approaches if governance issues arise during the guideline development process. The Gender Guidelines Governance Committee includes four experts in bioethics, health law, and systematic reviews.”
Is this a case of who guards the guards? One of the governance committee’s four members is the editor-in-chief of the Medical Journal of Australia (MJA), Professor Virginia Barbour. The issue is the institution, not the person.
In 2018, under a previous editor-in-chief, this journal published a peer-reviewed version of the RCH gender clinic guidelines with Dr Pang as a co-author. The peer reviewers and journal editors let through the startling RCH claim that, “The scarcity of high-quality published evidence on the topic prohibited the assessment of level (and quality) of evidence for these recommendations.”
I put this formula to a pioneer of the evidence-based movement in medicine, Gordon Guyatt, who was also central to the development of the GRADE system for rating evidence. For Professor Guyatt, the claim that evidence could not be rated was enough to conclude that the RCH guideline was untrustworthy. After all, GRADE ratings range from “high” and “moderate” certainty to “low” and “very low” certainty, with certainty meaning the level of confidence that the reported treatment effect is close to the true effect.
Everything about us
On Professor Barbour’s watch, the MJA published an October 2024 critique of the Cass Review, with Dr Pang as a co-author. This article complained that Dr Cass’s “Review team were explicitly selected for their absence of experience in trans health care, supposedly to avoid bias. Remarkably, in the era of nothing about us without us, no Review authors were trans people.”
The structure of the Cass Review was consistent with the UK tradition of an independent inquiry run by someone reputable with no skin in the game. But the Cass team did have various engagements with gender clinicians, setting up a Clinical Expert Group involving experts in child/adolescent development, gender-related issues, physical/mental health, safeguarding, and endocrinology. Dr Cass took responsibility as the author of the report, but during the Review her team also listened to the accounts of trans-identifying young people.
Another complaint in the 2024 MJA article was that the Cass Review “appeared to misunderstand the young person’s primary goal of puberty blocker treatment, which is to prevent progressive irreversible incongruent pubertal changes. It did not acknowledge the benefits of prevention of breast development for trans males, and prevention of facial masculinisation for trans females. Instead, the Review focused on secondary mental health outcomes.”
Is this a shifting of the goalposts, now that the shoddy state of the evidence base for the mental health promises of gender clinics has been exposed by multiple systematic reviews? The “transition or suicide” narrative can hardly be satisfied with only the predictable physical effects of blockers and hormones. In May 2022, the US assistant secretary of health, Dr Rachel Levine, expressed the orthodox view succinctly: “Gender-affirming care is medical care. It is mental health care. It is suicide prevention care. It improves quality of life, and it saves lives.”
Could it be that the NHMRC advice on puberty blockers and cross-sex hormones will try to compensate for the weak evidence by valorising a teenager’s “autonomy” in the medical pursuit of subjective “embodiment goals”?
And yet Dr Pang is not alone among gender clinicians in seeming unwilling to totally abandon the origin story of improved mental health. In September 2024, The Conversation website—with its motto “Academic rigour, journalistic flair”—published another gender-affirming polemic by Dr Pang and colleagues. They cited an unnamed systematic review and plucked from it the only high-quality (cross-sectional) study which “found significantly improved psychological outcomes. Puberty blockers reduced suicidal thoughts and actions in transgender adolescents compared to those who had not accessed the treatment.”
The article failed to mention that this systematic review was one of those assigned to the University of York by Dr Cass—and criticised elsewhere as unreliable by Dr Pang and other gender-affirmers. Now, for The Conversation, Dr Pang and colleagues had cherry-picked one study and ignored the York review’s overall conclusion. (Of 50 studies, 24 low-quality papers were excluded from the synthesis).
The first page of the York review delivers the verdict: “No high-quality studies were identified that used an appropriate study design to assess the outcomes of puberty suppression in adolescents experiencing gender dysphoria/incongruence.”
“There is insufficient and/or inconsistent evidence about the effects of puberty suppression on gender-related outcomes, mental and psychosocial health, cognitive development, cardiometabolic risk, and fertility.
“There is a lack of high-quality evidence to support the use of puberty suppression in adolescents experiencing gender dysphoria/incongruence, and large well-designed research is needed.”
The NHMRC webpage acknowledges Dr Pang’s foray into America’s health politics as a potential conflict. Why not also declare his MJA polemic and the cherry-picking article for The Conversation?
Can gender-affirming care and evidence-based medicine be reconciled?
GCN does not dispute that gender-affirming clinicians believe their interventions benefit vulnerable young people. GCN sought comment from Dr Pang.
In Queensland’s 2025 Vine Report on youth gender care, a report that arguably exaggerated the evidence, there are 77 references to the German guideline. This low-quality guideline is bracketed with the Cass Review as if it were equally credible, whereas Dr Cass based her findings on multiple systematic reviews.
In 2023, Professor Zepf and colleagues undertook an updated version of the 2020 systematic reviews of the evidence for blockers and hormones run by the UK National Institute for Health and Care Excellence (NICE).
The passage of time had not improved the very uncertain evidence base: “Current evidence does not clearly suggest that [gender dysphoria] symptoms and mental health significantly improve when [blockers] or [hormones] are given to minors with [gender dysphoria]. Children and adolescents with [gender dysphoria] should therefore primarily receive psychotherapeutic interventions that address and reduce their experienced burden.”
In response to the 2024 draft for Germany’s S2k guideline, the 126th German Medical Assembly passed a resolution in which the German Medical Association called on the country’s federal government to restrict puberty blockers, cross-sex hormones and trans surgery for minors to ethically controlled clinical trials with at least ten years’ follow-up.
Like other federal agencies, the NHMRC labours in the long shadow cast by the 2013 Australian Government Guidelines on the Recognition of Sex and Gender following amendments to the Sex Discrimination Act, which introduced the subjective concept of self-declared gender identity as a protected characteristic.
In 2025, the NHMRC issued a Statement on Sex, Gender, Variations of Sex Characteristics and Sexual Orientation in Health and Medical Research. This document’s circumlocutions betray the influence of gender ideology. For example: “A collection [of data] may instead ask for a person’s sex at the time of completing a survey, rather than their sex recorded at birth. However, there are advantages of sex recorded at birth as the sex question and further data that can be derived when using sex recorded at birth as the sex question.”
There is no clear statement that our reproductive sex is binary and immutable. The ill-defined term “non-binary” makes multiple appearances in the document.
In response to questions from GCN, the NHMRC confirmed that the interim advice on puberty blockers will be based on a systematic review. “The systematic evidence review will include a number of topics, including puberty suppression and gender-affirming hormones,” the council’s spokeswoman said. “NHMRC has contracted an external party to conduct a systematic review of evidence. They will be identified in both the interim advice and the full guideline.”
In the gender medicine lobby’s response to the NHMRC project, there is no sense that they have been caught out after several years’ promotion of the low-quality RCH guideline as a national benchmark, an undeserved status also conferred by the federal health bureaucracy until Mr Butler’s January 2025 intervention.
Another AusPATH member on this key committee is Simon Denny. That potential conflict is declared on the NHMRC guideline webpage, but there is no acknowledgment of the fact that Professor Denny is a member of the board of the Queensland Children’s Hospital, which has been responsible for a large gender clinic. A senior clinician of that hospital, child and adolescent psychiatrist Dr Jillian Spencer, has been raising concerns about the safety of the gender-affirming model. She has been issued with a termination notice, but is pursuing various legal options.
Very interesting article Bernard. Thank you for the work you do.