This editorial appears in the June 2025 issue of the American Journal of Bioethics.
Background
The correct approach to the care of children and young people who are questioning their gender or experiencing gender dysphoria is one of the most controversial issues of our time. Most authors agree that gender incongruence and dysphoria arise through a complex interplay of biopsychosocial and cultural factors, although the exact etiology, presentation and long-term outcome will be highly individualized. This makes it challenging to identify the most appropriate treatment for each young person.
Medical history is littered with disagreements over science, evidence and the appropriate management of a range of clinical conditions. However, the care of young people with gender incongruence or dysphoria has been characterized by polarized social and political debate overshadowing the scientific process. This has led to a neglect of the basic tenet of evidence-based medicine that serves as a research and practice lodestar to maximize benefit and avoid harm.
Some of the views are more aggressively voiced than in any other area of clinical care, such that many people are afraid to express an opinion; this is a dangerous situation for both doctors and patients. This problem is exacerbated by modern communication technologies which provide easily accessible tools and routes for the targeted dissemination of dangerously misleading statements and misinformation.
The UK Context
Policy and practice in the management of children and young people in the UK has changed in response to publication of The Independent Review of Gender Identity Services for Children and Young People (“the Cass Review”/“the Review”). In contrast to the situation in the US, where views about the correct approach to this area of medicine are split along partisan lines, the Cass Review has the support of both major political parties, with implementation being started under the previous Conservative government and continued under the current Labour administration. Much of the subsequent disinformation about the Cass Review in the US arises from a fundamental and profound misunderstanding about the commissioning and governance of independent reviews in the UK, lack of knowledge about UK regulatory processes, and disregard for the extensive stakeholder engagement processes. This is evidenced, for example, in a recent opinion piece in the New England Journal of Medicine, and a widely cited essay on the Yale Law School website which has subsequently been extensively debunked by a number of authors. Some of these errors are also reproduced in Kirby’s target paper in this issue.
Independent reviews are used in many countries to provide objective and impartial assessments of a concerning situation or process, ensure transparency and accountability, identify areas for improvement and make recommendations. In the UK, independent reviews are typically nationally commissioned; in the National Health Service (NHS) they are put in place when clinical practice threatens quality of care and patient safety. Review chairs are respected public figures with considerable professional experience and knowledge. In order to ensure independence, they have no ties to the specific area under review. The scope and purpose of an independent review, and the questions that it is required to answer are defined by the commissioning body rather than, as Kirby appears to expect, the chair. Final recommendations are made by the chair and are not pre-approved by either the commissioning body or UK government. The recommendations are written primarily for the commissioners and providers of services, but there is no mandate to develop clinical guidelines or direct regulation.
The Cass Review was commissioned by NHS England (NHSE), which is an arm’s length body, independent of the UK government. Dr Cass was selected because she had previously been President of the Royal College of Pediatrics and Child Health, had no political affiliations and no previous involvement or position on the subject of youth gender medicine. Some North American commentators have represented Dr Cass’s independence from the field of youth gender medicine as a weakness, whereas it is the Review’s key strength.
Dr Cass was initially asked to undertake a narrowly focused task; specifically, to chair a policy working group to evaluate the published literature on puberty blocking medication and masculinizing/feminizing hormones in the treatment of children and young people with gender dysphoria. This literature review was carried out by the National Institute for Health and Clinical Excellence (NICE). When the NICE systematic reviews of evidence revealed an inadequate evidence base for NHSE to form a policy position, the full independent review was commissioned. Further drivers for the commissioning of the Review were the dramatically increasing number of young people presenting to the single national Gender Identity Development Service (GIDS), a marked change in the demographic characteristics of the population and concerns about clinical practice within the service.
The bedrock of the Cass Review was seven systematic evidence reviews addressing key aspects of care for gender dysphoric youth. These were carried out by the University of York, which was appointed through an independent bidding process (known as “tendering” in the UK) based on the quality of their research proposal. The York reviews included an appraisal of the major international guidelines. Contrary to Kirby’s assertion that no new clinical research was performed, the Review also commissioned an audit of international practice, a qualitative study of views of adolescents, young adults, families and clinicians, a prevalence study in primary care and a linkage study to obtain follow up data into adulthood. Unfortunately, the latter could not be completed because the adult clinics refused to cooperate.
The systematic reviews demonstrated a remarkably weak evidence base underpinning current practice in the care of children with gender-related distress. The findings of the systematic reviews on medical treatments were replicated by two recent North American systematic reviews. The guideline appraisal demonstrated that the majority of international guidelines had not followed appropriate guideline development processes. Standards of Care (Version 8) from the World Professional Association for Transgender Health (WPATH), the most commonly cited international guideline, received amongst the lowest scores for rigor of development and editorial independence. Only the Swedish and Finnish guidelines were of sufficient quality to be recommended in practice. Importantly, these differ markedly from those of WPATH and recommend non-medical interventions such as psychosocial support as the first line intervention.
The stakeholder engagement processes utilized by the Cass Review are summarized in the final report and set out in full in the detailed engagement report. Over 1000 individuals were interviewed, including young people and adults with lived experience (either directly or as a family member), as well as professionals practicing in pediatric gender medicine and in broader aspects of child physical and mental health and wellbeing. Those with direct experience included individuals who had gone through a successful medical transition, with positive experiences of the treatment pathway, individuals who had remained gender-fluid or non-binary, and others who had gone through a period of trans identification that had resolved in late teens and/or early adulthood. This is consistent with accounts given to the Review by many national and international clinicians, who stated that they are unable to reliably predict which children/young people will transition successfully, which might regret or detransition at a later date and which might resolve their gender distress in other ways. It is also echoed in published literature. For example, Bachmann et al found diagnostic persistence over the 5-year follow-up period of less than 50% in all age groups, which they interpreted as reflecting the fluidity of gender identity in childhood and adolescence. Rawee et al found that gender non-contentedness peaked at around 19% at age 11 and fell off progressively to less than 2% in mid-twenties. Currently it is estimated that 3.3% of adolescents in the United States identify as transgender, and an additional 2.2% question whether they might be, but only a small minority (0.1%) go on to require medical treatment.
Clinical professionals who were interviewed by the Review were also clear that gender-related distress had be seen within the wider context, noting that there has been a substantial increase in rates of mental health problems in children and adolescents across the United Kingdom over the past decade, with increased anxiety and depression being most evident in teenage girls, and a rise in young people presenting with other bodily manifestations of distress; for example, eating disorders, tics and body dysmorphic disorder. All these factors have potential impacts on young people’s evolving sense of self and identity.
The Review concluded that this group of children and young people had been exceptionalised because healthcare professionals had become fearful about following the same assessment processes that they would for any other young person in distress, instead believing that anything other than unquestioning affirmation would result in them being labeled as transphobic. As a result, many patients had not received the same standard of basic care that would be afforded to other similarly distressed adolescents; for example, treatment of depression or anxiety, diagnosis of neurodiversity, or support when they were unable to attend school or had suffered family breakdown. Furthermore, a lower standard of evidence had been used to guide treatment decisions than would be expected in other areas of pediatric practice.
The Review’s recommendations were aimed at redressing these problems by increasing the number of centers providing assessment and a much more holistic patient-centred model of care for these young people, establishing multi-disciplinary assessment processes, and advising that all interventions—both medical and non-medical—should be given within a research context that would improve the evidence base upon which young people and their families could base life changing decisions. The underpinning aim was that wherever in England a child or young person accesses services, they should receive the same high standard of evidence-based care.
Applying Ethical Principles in Gender Identity Services for Children and Young People
Kirby’s paper applies 4 ethical lenses to the approach to care for children and young people presenting to gender identity services; individual and relational autonomy, comparative patient welfare considerations, health equity, and justice.
Placing autonomy ahead of comparative patient welfare considerations is an unusual stance because certainly in UK practice, patient welfare considerations are paramount. This is not just a UK position; according to Beauchamp & Childress, the most cited US textbook in bioethics, autonomy has no higher status than the other medical ethics principles, such as beneficence and non-maleficence. In the UK, the General Medical Council guidance states that a doctor may only prescribe a medicine if they have adequate knowledge of the patient’s health and are satisfied that the medicine serves the patient’s needs; this is challenging in the face of diagnostic uncertainty and a weak evidence base. The Medicines and Healthcare Products Regulatory Agency (the UK equivalent of the US Food and Drug Administration) advises that “the responsibility that falls on healthcare professionals when prescribing an unlicensed medicine or a medicine off-label [as is the case for puberty blocking medications] may be greater than when prescribing a licensed medicine within the terms of its licence”. The guidance goes on to say that prescribers should pay particular attention to the risks associated with using unlicensed medicines or using a licensed medicine off-label. Furthermore, guidance on assessing best interests in prescribing for children states that the practitioner must take account of multiple factors including which choice, if there is more than one, will least restrict the child or young person’s future options. In other words, if the practitioner believes that the risks outweigh the benefits of a treatment, or that the treatment is not in the best interests of the patient, then autonomy is not a consideration, because the practitioner is professionally unable to prescribe. To do so would equate to considering that smoking cigarettes is not in a child’s best interests but still allowing them to smoke on the basis of autonomy. In fact, smoking is a good example of applying a precautionary approach to safeguarding children’s welfare; sales of tobacco to persons under 16 were prohibited in the Children’s Act 1908 in the UK, but the Doll and Hill report on the relationship between smoking and lung cancer did not appear until 1950.
In assessing the “comparative patient welfare considerations,” Kirby makes an assessment of the risk/benefits of medical treatments based on a personally selected sample of the very large number of publications in this area and concludes that in his opinion “current comparative analysis of the benefits and burdens of GAC for youth supports continued use of a version of the gender-affirming care model for youth who present with significant distress secondary to marked and persistent gender-incongruence.” Several of Kirby’s selected references were assessed to be low quality, and therefore unreliable, by the systematic reviews conducted by the University of York for the Cass Review. Again, Kirby’s approach to assessing the risk/benefit of a treatment is highly unusual, and not one that would be acceptable for other serious life changing medications, such as cancer treatments. Patients would rightly expect that decisions about risk/benefit would be based on a critical analysis of the literature through systematic reviews rather than an arbitrary selection of a handful of papers.
The conclusion of the Cass Review, which was based on both systematic reviews and extensive stakeholder and professional consultation, was much more cautious. It recognized the lack of good quality studies and the inadequate follow-up of the population, and recommended that puberty blockers should only be provided within the context of a research framework, and that extreme caution should be exercised in prescribing masculinizing and feminizing hormones to under-18s. It also recommended that prospective consent should be sought from all patients entering the service to participate in long term research and follow up for the full range of interventions.
Autonomy of the young person and views of parents and carers are of course key strands of the joint decision-making process for any treatment—psychological or medical—that might be offered to patients if the clinician feels that it may be appropriate for their needs. The Cass Review acknowledged that a medical pathway may be the best option for some patients, and discussed some of the practicalities and dilemmas in obtaining informed consent in the face of uncertainty. Getting this right will be crucial in engaging young people and their families in future research.
Patient engagement in planning future research priorities is also essential, and the NHS has engaged the James Lind Alliance (JLA) to help with this. JLA is a nonprofit making initiative bringing patients, carers and clinicians together to identify and prioritize unanswered questions that they agree are the most important, so that researchers and funders are aware of the issues that matter most to the people who need to use the research in their everyday lives.
With respect to any future research, Kirby does not appear to appreciate that blinded randomized controlled trials (RCTs) and unblinded RCTs are two different designs. He states that the Cass Review paid particular attention to the paucity of RCTs, and goes on to say that “RCTs are methodologically inappropriate and cannot be effectively performed as participants in the inactive arm recognize relatively early on that they are not enrolled in the active/experimental arm”. In fact, at no time did the Cass Review call for RCTs—blinded or unblinded—as the only form of high-quality evidence, either in the published literature which underpinned the systematic reviews or in future research. The main deficiency in the published research was not the lack of RCTs, but rather that most of the studies were just poor quality; there were high rates of loss to follow up, inadequate follow up periods, poor descriptions of confounding variables, and inadequate descriptions of comparator cohorts.
Kirby is right to raise the issue of research injustice, but rather than the implied criticism that too high a standard is set for research in this area, the real injustice is that children and young people have been offered interventions based on a lower standard and quality of research than in other areas of pediatric practice. The quality of research in this area would not be deemed acceptable for children and young people receiving chemotherapy, psychotropic medications or cardiac surgery; it should not be acceptable for this already disadvantaged group of young people.
Finally, Kirby’s concern about the injustice of political interference is an important point of discussion. There is clearly extreme politically driven hostility to the trans community in the US, and it is hard to imagine or under-estimate the trauma, distress and fear that this must be causing. Sadly, the US is not alone in this respect, and across the world trans people are at risk politically, socially and in terms of serious health inequalities.
However, while Kirby’s assertion that there is political opposition to gender affirming care in the US is borne out by the facts, he has no basis to make this assertion in relation to care in Scandinavia or the UK, nor does he provide any evidence to support this claim. The common feature in Scandinavia and the UK has been a reliance on independent systematic reviews of the evidence, curiosity about the factors driving an increase in demand for medical treatments, and a cautious research-driven approach to future care. In the UK the Cass Review has had support from the major political parties, and from the medical Royal Colleges, which are responsible for professional standards. The UK government and NHS leadership have committed to a three-year implementation plan.
“More in Common” is an international initiative set up in 2017 to build societies and communities that are stronger, more united, and more resilient to the increasing threats of polarization and social division. In 2022 they conducted targeted quantitative and qualitative research on 20,000 Britons from across the political spectrum to understand their attitudes to gender identity, trans issues and sex- and gender-based rights. They found that few approach these topics from rigidly political, binary, or ideological lenses. Instead, they see a series of practical issues requiring practical solutions. Most people’s instinct is “live and let live”—they believe trans people should be respected, supported and given the space to make their own choices. However, a majority of Britons believed medical interventions toward transition should not start below the age of 18. In the UK, there is a sense of social justice, but also an instinct to protect young people during a vulnerable period in their development.
Disclosure Statement
Camilla Kingdon is chair of the National Provider Network, which is the body overseeing functioning of the new regional children’s and young people’s gender identity services. Hilary Cass was chair of the UK Independent Review of Gender Identity Services for Children and Young People.