The Cass Review and Gender-Related Care for Young People in Canada: A Commentary on the Canadian Paediatric Society Position Statement on Transgender and Gender-Diverse Youth

The Canadian Paediatric Society Position Statement (CPS-PS), “An affirming approach to caring for transgender and gender-diverse youth,” (Vandermorris & Metzger, 2023) requires reconsideration. The CPS-PS describes gender identity as a “critical facet of a young person’s sense of self” (p. 439) that emerges in early childhood and evolves over time. Although it states that gender identity evolves, it makes no mention of the desistance and detransition literature or of the mental health comorbidities that may impact gender identity. The absence of any such discussion implies that gender identity development is linear and stable, reinforcing a model in which transition is understood to be a natural trajectory for youth with gender incongruity. The CPS-PS, therefore, directs pediatricians to center the “adolescent’s expertise in their own life experience” (p. 440) and proposes that doctors affirm a patient’s self-described gender identity and provide access to medical transition. The stated clinical role of the doctor is presumably not to engage in the etiology of gender distress to determine if transition is appropriate, but to facilitate the process by “support[ing] the adolescent in identifying and moving along the trajectory that best aligns with their individual goals” (p. 440).

This approach raises questions about clinical neutrality, diagnostic rigor, and safeguarding of informed decision-making. The endorsement of the treatments outlined in the CPS-PS implies that the benefits of gender-affirming treatments in children and adolescents are known, that they clearly outweigh the risks, and that young people are able to weigh such explicitly described risks and benefits in order to give informed consent. Here, we outline pertinent information Canadian physicians need to know about puberty blockers (PBs) and gender-affirming hormone therapy (GAHT) that are not covered in the CPS-PS. We also discuss critical information that should inform the care of gender-distressed young people, including the rapid rise of gender dysphoria over the last decade, the clinical presentation of these young people, and the literature on identity development, desistance, and detransitioners.

Rights-Based versus Evidence-Based Approach to Treatment

A recent international conspectus of treatment models for gender dysphoria in children and adolescents found that these models lay on a continuum from a rights-based approach to an evidence-based approach (Kozlowska et al., 2024). The CPS-PS adopts a rights-based approach, emphasizing destigmatization, depathologization, centering patient autonomy, and support for the fulfillment of patient goals and self-determination. Under this rights-based model, a comprehensive biopsychosocial assessment prior to medical transition is often considered unnecessary (Ashley, 2019a; Oosthoek et al., 2024). The evidence-based approach emphasizes patient safety and the effectiveness of offered treatments in promoting long-term improvements in health. While this approach highly values patient autonomy, this is balanced by sound scientific research findings (i.e., evidence) and clinical expertise with a strong grounding in beneficence and non-maleficence.

In evidence-based medicine, the best available evidence, ideally from systematic reviews, is used to assess the benefits and risks of interventions. This systematically considered evidence, along with patient values and preferences and clinical expertise, is used to make treatment decisions (Guyatt et al., 2015). In the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, research evidence is evaluated according to factors such as risk of bias arising from methodological limitations, imprecision of estimates, indirectness of the evidence, inconsistency of results, and publication bias. The certainty of evidence is rated as high, moderate, low, and very low based on these factors. Evidence from randomized controlled trials is initially rated high but may be rated down due to factors such as inadequate blinding or missing data. Evidence from observational studies is typically rated low but may be rated up based on large effect sizes, evidence of a dose–response relationship, or the use of methodologies that control confounding. Thus, GRADE may be used to evaluate evidence generated from various research designs. With high certainty evidence, further research is unlikely to change the degree of confidence in the estimates of effects from a treatment. With low certainty evidence, further research is very likely to change the estimates of effect (Guyatt et al., 2008) and “there is very little confidence in the effect estimate and the true effect may be substantially different” (Balshem et al., 2011, p. 404). Thus, with very low certainty evidence, there is no way to rule out benefit or harm for the intervention.

The Cass Review

The Cass Review was an independent evaluation of gender identity services for children and adolescents in the UK, commissioned by the National Health Service (NHS) England in response to concerns about clinical practices at the Tavistock Clinic’s Gender Identity Development Service (Barnes, 2023; Evans, 2020). The review, led by Hilary Cass, a former president of the Royal College of Paediatrics and Child Health (2012–2015) and Chair of the British Academy of Childhood Disability (2017–2020), was the culmination of nearly four years of work consisting of commissioned research, consultations with clinicians and other allied professionals, meetings and focus groups with patients, their parents, and advocacy groups, and a review of international clinics. The final report included both a general discussion of pediatric gender medicine and specific service recommendations for NHS England (Cass, 2024b).

Key findings and recommendations of the Cass Review were as follows:

1. The polarization of transgender issues created a challenging work environment, impeding the ability to consistently provide holistic care.

2. Most clinical guidelines, including the Endocrine Society Guidelines (ESG), World Professional Association for Transgender Health Standards of Care Version 7 (WPATH SOC-7) and 8, and the American Association of Pediatrics Position Statement (AAP-PS), are low quality and not recommended.

3. The evidence for the benefit of social transition, puberty blockers, and cross-sex hormones is very low/low certainty/ quality.

4. There is no evidence on long-term outcomes of children who received gender-affirming care.

5. A new treatment model was recommended, which includes a comprehensive assessment, differential diagnosis and focus on psychological support, with medical transition used with rigorous oversight and only in a research setting.

Criticisms of the Cass Review

The authors of the CPS-PS claimed that the Cass Review suffered from methodological flaws (Vandermorris et al., 2024), stating (falsely) that “[m]any studies were excluded from the systematic reviews commissioned by the Review because they did not meet the ideal methodologic standard–randomized controlled trials, blinded studies, and multi-institutional research” (p. 416). In fact, the systematic reviews considered 103 non-randomized observational studies and used the Newcastle–Ottawa Scale, a tool designed to assess the methodological quality of such studies. Only two of these observational studies were rated high quality, and 58% of them were deemed of sufficient quality and included in the Cass Review's synthesis (Cass, 2024a).

Vandermorris et al. (2024) pointed to critiques of the Cass Review by McNamara et al. (2024) and Noone et al. (2025). A response to these critiques argued that they misrepresented the role and process of the Cass Review and that their methodological critiques were unfounded (Cheung et al., 2024). A central criticism raised by both commentaries was that the Cass Review was led by a single individual with no experience in gender-affirming care. However, Cheung et al. (2024) noted that UK independent reviews are typically conducted by “a respected public figure with no ties to the area under review” (p. 252). Such independence is intended to minimize bias. McDeavitt et al. (2025) fact-checked various critiques of the Cass Review and found that they “made claims which were inaccurate, or which lacked essential clarification/contextualization.” Clayton et al. (2024) responded to some criticisms of the Cass Review and discussed its application to Australia, which has policies and practices like those in Canada. Kingdon et al. 2025 have also responded to the common criticisms of the Cass Review. We do not reproduce all of these responses other than to note here that others have quite adequately defended the Cass Review methodology.

Shortcomings of the Canadian Paediatric Society Position Statement

In reaffirming the CPS-PS, Vandermorris et al. (2024) stated that “the approach to gender-affirming care for adolescents in Canada remains grounded in the tripartite approach to evidence-based practice… available evidence, clinical expertise, and patient and family goals and values…and remains unaltered by the publication of the Cass” (p. 416). However, it is unclear why this should be the case. Evidence-based guidelines must be grounded in a systematic review of the evidence. The Cass Review found that the evidence base for gender-affirming care for youth is “remarkably weak” and brought into question the quality and credibility of the WPATH SOC and ESG positions, which the CPS-PS relied on. The Cass Review highlighted how the results of a single study on the treatment of a narrowly defined group of children became quickly adopted and applied more generally to all young people experiencing gender distress, leading some clinicians to abandon prudent, conventional clinical practice. It also highlighted the lack of consensus among clinicians treating this population, the precipitous rise of gender dysphoria, and the emerging literature on detransition.

The findings of the Cass Review highlight many shortcomings of the CPS-PS. The CPS-PS:

1. Is based on clinical guidelines which the Cass Review found to be unreliable;

2. Treats gender identity as a stable characteristic and, in doing so, ignores the history of the development of gender distress in young people, the research on desistance and detransition, and the interconnection between gender-related distress and comorbid mental health conditions;

3. Has no discussion of the precipitous rise of young people, particularly adolescent girls, most with mental health comorbidities and/or neurodevelopmental conditions, identifying as transgender in the last decade;

4. Has no discussion of the growing literature on regret or detransitioners and how the experiences of detransitioners could inform clinical practice;

5. Overstates the benefits and understates the risks of puberty blockers and gender-affirming hormone therapy; and

6. Ignores the complex issues of obtaining genuine informed consent for gender-affirming treatments.

Reliance on Unreliable Guidelines

The Cass Review commissioned two systematic reviews of all policy documents published between 1998 and 2022 that serve as clinical guidelines for children and young people experiencing gender dysphoria to assess the quality of guideline development and the reliability of treatment recommendations using the Appraisal of Guidelines for Research and Evaluation (AGREE II) (Taylor et al., 2024a, 2024b). The guidelines included the 7th and 8th editions of the WPATH Standards of Care (Coleman et al., 2012, 2022), the AAP policy position (Rafferty et al., 2018), the ESG (Hembree et al., 2009, 2017), national guidelines from Finland (Council for Choices in Healthcare in Finland, 2020) and Sweden (The Swedish National Board of Health & Welfare, 2022), and 18 other guidelines (Hoffmann-Eßer et al., 2018). It was found that “[m]ost clinical guidance lacks an evidence-based approach and provides limited information about how recommendations were developed” (Taylor et al., 2024a). WPATH SOC-8, the most widely cited and most influential of guidelines, scored among the lowest for developmental rigor and editorial independence. Except for the Swedish and Finnish guidelines, which followed rigorous practices, all other guidelines contained high degrees of circular referencing. Rather than conducting independent reviews of evidence, most guidelines relied on the WPATH SOC and the ESG, leading Cass to note: “These two guidelines are closely interlinked, with WPATH adopting Endocrine Society recommendations, and acting as a co-sponsor and providing input to drafts of the Endocrine Society guideline” (Cass, 2024b, p. 130).

Although the CPS-PS was not included in the commissioned systematic review, as it was published after the December 31, 2022 deadline, it relied heavily on the ESG (Hembree et al., 2017), the AAP-PS (Rafferty et al., 2018), and the WPATH SOC-8 (Coleman et al., 2022), all of which failed to follow rigorous, transparent guideline development practices.

WPATH SOC-8 was also criticized for failing to use the systematic reviews that it had commissioned, three of which were on adolescents, that found only low certainty evidence that hormone therapy was associated with improved measures of psychological well-being and quality of life (Baker et al., 2021), but instead, adopted a consensus-based approach to make strong recommendations for hormone therapy that “overstat[ed] the strength of the evidence” (Cass, 2024b, p. 130). As Guyatt, one of the founders of evidence-based medicine, has noted, “systematic reviews are meant to ensure that doctors’ recommendations are based on objective evidence, not ‘habit or misguided expert advice’” (Confessore, 2025). Systematic reviews support sound guideline development and clinical decision-making by countering bias. The lack of reliance on systematic reviews coupled with strong recommendations, which should only be made when benefits of the treatments clearly outweigh the risks, makes WPATH SOC-8 and other guidelines based on it, not evidence based (Confessore, 2025).

Since the publication of the Cass Review, further evidence has emerged that WPATH disregarded the principles of evidence-based guideline development. WPATH SOC-8 first included recommended minimum ages for hormonal treatments and surgeries; however, shortly after publication, a correction was issued, removing all age recommendations, except for a minimum age of 18 for phalloplasty (“Correction,” 2022). Although WPATH did not provide any explanation for the changes, internal WPATH documents disclosed in pre-trial discovery in the United States Federal Court case of Boe v. Marshall revealed that WPATH removed the minimum ages from SOC-8 due to political pressure from the United States Department of Health and the American Academy of Pediatrics (Ghorayshi, 2024; Singal, 2024), and not on the basis of scientific evidence or even expert consensus.

Disclosed documents also revealed that WPATH had commissioned a series of systematic reviews from Johns Hopkins University regarding 13 review questions to inform the development of SOC-8 (Sharma et al., 2018) but had only published two of these reviews. The internal emails revealed that WPATH had restricted the ability of the Johns Hopkins researchers to publish the results of the systematic reviews and, after the first review was published, insisted on an approval process which gave WPATH veto power over the contents of the reviews (Block, 2024; The Economist, 2024).

Limited Conceptualization of Gender Identity

The CPS-PS did not adequately consider the development of a sense of gender identity. While it stated that “emerging theoretical and empirical studies that employ multidimensional and dynamic constructs of gender may afford more nuanced insights into this domain, throughout the life course” (Vandermorris & Metzger, 2023, p. 439), it disregarded these theoretical perspectives, and empirical evidence, and instead endorsed an affirmation model based on the young person’s current understanding of their gender identity.

The underlying assumption of the affirmation model, espoused by WPATH SOC-8 and endorsed by the CPS-PS, is that gender identity is stable or at least stable enough to warrant treatment that can result in permanent changes. This assumption is challenged by desisters, detransitioners, and the recent rapid increase in the number of young people presenting with gender distress. Historically, gender dysphoria emerging post-puberty was rare and most commonly presented in young children with a significantly higher prevalence in natal males (Zucker et al., 2012a). Beginning in the early 2000s, the number of referrals to gender clinics began to rise, with a precipitous rise beginning in 2014 and a sex ratio favoring natal females at ratios from 2:1–3:1 (Aitken et al., 2015; Becerra-Culqui et al., 2018; Butler et al., 2018; Cass, 2024b; Kaltiala-Heino et al., 2018). Figure 1 shows that this pattern has been observed across the Western world, including Canada (Taylor et al., 2024c). Further, these young people present with comorbid mental health and neurodevelopmental conditions or a history of trauma with prevalence rates significantly higher than those observed in the general population of children and adolescents (Taylor et al., 2024c).

Fig. 1.

Number of referrals over time by country.

Source: Taylor et al. 2024c, used by permission

The Cass Review noted that “[t]here is broad agreement that gender incongruence, like many other human characteristics, arises from a combination of biological, psychological, social and cultural factors” (Cass, 2024b, p. 26) and that while greater societal acceptance of trans identities may partially explain the rise of referrals, it is unlikely to explain it entirely. Acceptance cannot explain the sex ratio reversal and why those with mental health and neurodevelopmental conditions are overrepresented. The rapid and dramatic increase in population incidence also suggests that greater societal acceptance is unlikely the main explanation. The dramatic temporal trend highlights further areas of investigation, such as whether mental comorbidities are causal or consequential, as well as the impact of social influences (peer and online) and other stressors. It is worth noting that the gender-affirming model fails to consider how all these factors may contribute to gender experience and distress, as the underlying assumption of the affirmation model is that there is simply a mismatch between one’s sex and one’s gender identity.

Persistence and Desistance

The CPS-PS ignored research that has found that gender-related distress or incongruence in children is rarely permanent, often resolving during puberty or early adulthood, with many individuals later identifying as gay or lesbian (Bachmann et al., 2024; Drummond et al., 2008; Green et al., 1987; Money & Russo, 1979; Singh et al., 2021; Steensma et al., 2011, 2013; Zucker, 2018; Zuger, 1984). If childhood gender dysphoria continues during puberty, some gender-affirming clinicians (de Vries et al., 2014; Rafferty et al., 2018; van der Loos et al., 2023a) have posited that it will persist into adulthood. However, as Byrne (2024) argued, there is no evidence for this conviction and the rate of persistence into adulthood remains unknown. The claim that persistence of gender distress into adolescence is predictive of life-long gender dysphoria is also challenged by detransitioners, who experienced dysphoria through adolescence, but their dysphoria resolved in adulthood (Littman, 2021; Vandenbussche, 2022).

Most studies of gender dysphoria in children were conducted at a time when social transition was discouraged. In a more recent study of children who had socially transitioned, 97.5% continued to identify as transgender 5 years later (Olson et al., 2022). Thus, the high rate of desistance shown in numerous earlier studies may be a reflection of the stigma of the time, or perhaps more likely, as the Cass Review suggested, “it is possible that social transition in childhood may change the trajectory of gender identity development for children with early gender incongruence” (Cass, 2024b, p. 164). This concern has been raised by others (Zucker et al., 2012b) and was raised in the early Dutch literature (Steensma et al., 2011).

We have little data regarding the new cohort whose gender dysphoria first presented post-puberty, but the few studies of detransitioners indicated that an approach that allows for more open-ended exploration and reflection, rather than affirmation, might better serve all individuals to make more informed decisions (Irwig, 2022; Littman, 2021; Littman et al., 2024; Vandenbussche, 2022).

Detransition

The CPS-PS overlooked regret and detransition. The rate of detransition is unknown (Cohn, 2023), especially among recently observed adolescent-onset cases. Studies define detransition in multiple ways leading to widely differing estimates ranging from 0 to 30% (Expósito-Campos et al., 2023). Studies reporting low detransition rates typically suffer from multiple limitations such as short follow-up periods, very high loss to follow-up, highly restrictive definitions, and biased samples (Cohn, 2023). Gender clinic data are likely to underestimate detransition rates as detransitioners are often reluctant to return to clinics that facilitated their medical transition due to fear of judgment or dismissal, and concerns of stigma (Littman et al., 2024; MacKinnon et al., 2023). A recent study of participants referred to an adult Finnish gender clinic for detransition over a 2-year window reported that the number of detransitioners appeared to be growing and that the time to detransition may be decreasing. All the natal female detransitioners experienced major regret (e.g., dysphoria due to new appearance or desire for detransition surgery). None of the detransitioners reported external reasons, such as discrimination, for detransitioning (Kettula et al., 2025).

Biopsychosocial Assessment and Co-Morbidities

The CPS-PS recommended a biopsychosocial assessment prior to commencing PBs or GAHT but fails to specify its purpose, what such an assessment must entail, which clinical discipline is best suited to conduct it, or how a comprehensive assessment seeking to uncover factors contributing to gender distress is consistent with a gender-affirming model. It is worth noting that the cautious comprehensive assessment model advocated by Zucker et al. (2012b), which involves clinical interviews with youth and their families, psychological testing, and input from parents and teachers to develop a multifactorial case formulation that accounts for co-occurring conditions and avoids premature closure—shares key features with the approach recommended by the Cass Review. Cass calls for a holistic evaluation of biological, psychological, and social contributors to gender-related distress, conducted by a multidisciplinary team with careful screening for neurodevelopmental and mental health conditions to ensure individualized care. Despite their clinical rigor, such approaches have been increasingly criticized as non-affirming and even framed as gatekeeping and conversion therapy due to their departure from an affirming approach (Ashley, 2019b; Ehrensaft et al., 2018; Rafferty et al., 2018; Temple Newhook et al., 2018).

Further, legislation targeting “conversion therapy” can hinder clinicians from offering comprehensive care to gender-distressed youth. While psychotherapy—aimed at fostering self-understanding and informed decision-making—is distinct from discredited efforts to change sexual orientation (D’Angelo, 2023), the legal boundaries remain unclear. Despite exemptions in most laws, including Canada’s, the vague scope of both prohibitions and protections leaves clinicians uncertain whether anything short of automatic affirmation qualifies as conversion therapy (Sinai & Sim, 2024). The CPS-PS’s unequivocal endorsement of affirmation may further discourage thorough assessment. The Cass Review highlighted similar concerns in the UK, where clinicians feared that standard therapeutic approaches could be misclassified as conversion practices, and recommended safeguards in legislation to protect clinical judgment (Cass, 2024b, p. 202). The Cass Review’s call for holistic, individualized care—including screening for neurodevelopmental and mental health conditions—has since been adopted by NHS England (Cass, 2024b, p. 148; Hayward, 2025).

The CPS-PS was based on a limited understanding of the interrelation between gender dysphoria and other mental health and neurodevelopmental conditions. The CPS-PS noted that “Transgender or gender-diverse youth are at elevated risk of adverse health outcomes, including depression, anxiety, eating disorders, self-harm, and suicide” (Vandermorris & Metzger, 2023). It asserted that these conditions can be explained “in part” by minority stress, the social stigma associated with gender nonconformity. It failed to consider that gender dysphoria, as pointed out in the Cass Review, may be secondary to these mental health conditions and/or traumatic events preceding the onset of gender dysphoria. The CPS-PS did not address the elevated rates of neurodevelopmental conditions such as autism spectrum disorders and attention-deficit hyperactivity disorder frequently associated with gender distress (Kallitsounaki & Williams, 2022; Lehmann et al., 2020; Warrier et al., 2020), which cannot be explained by minority stress.

In studies of detransitioners, many reported that their gender dysphoria, and subsequent transgender identity, was a result of other factors such as mental health issues, neurodiversity, trauma, difficulty accepting their sexuality, misogyny, or confusing sexuality with transgender identity (Littman, 2021; Littman et al., 2024; MacKinnon et al., 2023; Vandenbussche, 2022). The majority (56.7%) of detransitioners in one study reported they felt they were inadequately assessed before being approved for transition (Littman, 2021). A recent study of detransitioners reported that although patients accurately presented their mental health challenges, and were often diagnosed with multiple psychiatric conditions, they were, nonetheless, cleared for gender transition, highlighting how a focus on affirmation and centering a young person’s request may hinder holistic care and result in diagnostic overshadowing (Kettula et al., 2025).

Although gender-distressed young patients frequently present with mental health comorbidities (Becerra-Culqui et al., 2018; Cass, 2024b), primary care providers typically do not conduct holistic assessments or treat these conditions, opting to refer patients to gender clinics (Bonifacio et al., 2019). Unfortunately, gender clinics typically only assess readiness for PBs and GAHT (Transgender Youth Clinic, n.d.) and do not provide therapeutic open-ended exploration of the causes of the gender distress. Data from 10 hospital gender clinics across Canada showed only 45.6% of patients had been seen by a psychologist or psychiatrist (though it is unclear for how long and whether an exploratory or affirmative approach was used) before visiting a gender clinic; yet, 62.4% received PBs on their first visit (Bauer et al., 2021). An investigation by Radio-Canada found that a 14-year-old girl could get a prescription for testosterone at a private clinic in 10 min (Turbide, 2024). Research has also highlighted detransitioner reports that gender clinic staff had been overly enthusiastic in supporting medical transition (Expósito-Campos, 2021) or even tried to convince patients that they are transgender (Kettula et al., 2025). Although detransitioner accounts are current perspectives of past events, and memories are not always reliable, it is prudent to consider these narratives.

Puberty Blockers

The use of PBs for gender dysphoria is based on two studies of a cohort of carefully selected patients who first experienced gender distress in early childhood. The treatment protocol, known as the Dutch Protocol, consisted of PBs at the age of 12, gender-affirming hormones at age 16, and surgeries at age 18 (de Vries et al., 2011, 2014). Before beginning puberty suppression, all participants were extensively evaluated by an interdisciplinary team to ensure participants’ psychosocial functioning was adequate and to rule out any serious psychiatric comorbidities. All patients received psychological support in addition to medical transition and had the support of parents.

These studies have faced significant criticism for methodological shortcomings. Although the study began with 196 patients, only 70 were reported in the first study, and 55 in the second, with complete data for only 40, resulting in critical attrition bias. Notably, the final group excluded 3 patients who developed diabetes/morbid obesity, and one who died due to postsurgical necrotizing fasciitis. Key limitations included the lack of a control group, concurrent psychiatric support for all patients (a possible confounder compared to current practice), and a lack of physical health outcomes assessments (Abbruzzese et al., 2023). Despite these flaws, the protocol was rapidly extended to a broader population: adolescents whose gender distress emerged during or post-puberty, individuals with unmanaged comorbid mental health conditions (Biggs, 2023; Cass, 2024b), and patients whose parent involvement is considered unnecessary. Increasingly, parent concerns are dismissed as misinformed (Kirby, 2025; Knudson et al., 2022) and their involvement considered unnecessary (Priest, 2019).

The CPS-PS made claims about PBs that are not supported by evidence, overstated their benefits, and understated their risks. It asserted that PBs “provide a young person with time to further explore their gender identity” (Vandermorris & Metzger, 2023, p. 443), a claim rooted in the Dutch research. The Cass Review questioned this assumption, noting that “the vast majority of those who start puberty suppression continue to masculinising/feminising hormones” (Cass, 2024b, p. 176). Multiple studies report continuation rates to subsequent hormone therapy exceeding 95% (Brik et al., 2020; Butler et al., 2022; Carmichael et al., 2021; Kuper et al., 2020; Nyquist et al., 2024) suggesting either near-perfect predictive accuracy or that the treatment itself may influence identity development. Such precision, however, is not achievable in clinical practice (Bridley et al., 2020). If PBs were truly neutral, much greater variability in outcomes would be expected. Cass (2024b) hypothesized that early intervention may prematurely alter the natural trajectory of identity formation and, because there is no true separation of consenting to PBs and GAHT, this “means that young people have to understand their identity and sexuality based only on their discomfort about puberty and a sense of their gender identity developed at an early stage of the pubertal process” (Cass, 2024b, p. 178). Further, since sex hormones are integral to brain development (Aoki et al., 2017; Larsen & Luna, 2018; Romeo, 2013; Sisk & Zehr, 2005), particularly during critical periods of development such as puberty (Ernst et al., 2009), it has been hypothesized that PBs may impair a young person’s ability to assess the subsequent decision to begin GAHT when that time arises (Baxendale, 2024).

The CPS-PS asserted that PBs are reversible, implying their use has limited risk (Vandermorris & Metzger, 2023), which is also not supported by evidence. While PBs used for precocious puberty allow normal development to resume when discontinued at the appropriate time (Soliman et al., 2023), this cannot be extrapolated to the initiation of PBs during the normal window of puberty. While reversibility may refer to the fact that the hormone axes will resume their function once PBs are discontinued, the effects that occurred on end-organs during a critical period of development are an entirely different matter. Early Dutch research raised questions regarding suppressing puberty during the normal period of development, which included the effect on bone density, body composition, and cognitive development (Delemarre-van de Waal & Cohen-Kettenis, 2006), and significant gaps in knowledge still remain regarding how long PBs may be used safely as well as how long-term use may affect neurocognitive development (Chen et al., 2020; Clark et al., 2025). Framing PBs as simply reversible oversimplifies their impact and reflects an atomistic view of adolescent development.

None of the seven citations in the CPS-PS supported the assertion that PBs are reversible when used during the normal window for puberty. The first citation was WPATH SOC-8 (Coleman et al., 2022), which in turn cited a case report of two adolescents, one who was untreated due to insurance denial and the other who progressed to cross-sex hormones (Rosenthal, 2014). The second cited the ESG (Hembree et al., 2017), which cited articles on PBs to treat central precocious puberty (Bertelloni et al., 2000; Magiakou et al., 2010; Pasquino et al., 2008), and two articles on men with gonadotropin deficiency (Büchter et al., 1998; Liu et al., 1999), contexts unrelated to typical adolescent development. The third reference (de Vries et al., 2011) provided no data on reversibility as all patients in this study either proceeded to cross-sex hormones or were lost to follow-up. The remaining citations (Cohen-Kettenis et al., 2011; Costa et al., 2016; Delemarre-van de Waal & Cohen-Kettenis, 2006; Kreukels & Cohen-Kettenis, 2011) were commentaries on the study described in deVries et al. (2011) and contained no new evidence.

Puberty is a critical developmental window involving multiple interrelated physical, cognitive, and social changes. Hormone suppression during this period has risks which have been recognized but not adequately studied. The CPS-PS briefly acknowledged some of these risks but offered limited discussion. Nearly 90% of peak bone mass, an important predictor of the risk of later osteoporosis, is gained during puberty. Administration of PBs disrupts this process, slowing the accrual of bone mineral density (BMD) when it should be increasing most rapidly. While the CPS-PS noted that partial recovery may occur with GAHT (Biggs, 2021; Chuncia-Ileczko et al., 2025; Joseph et al., 2019; Klink et al., 2015; Schagen et al., 2020; van der Loos et al., 2023b; Vlot et al., 2017), findings are mixed. Studies suggest transboys (natal females) who proceeded to long-term testosterone therapy may regain BMD; transgirls (natal males) showed persistent deficits with long-term estrogen therapy (Chuncia-Ileczko et al., 2025; Schagen et al., 2020; van der Loos et al., 2023b). Other studies have found that BMD remained below pretreatment despite hormone therapy (Klink et al., 2015; Stoffers et al., 2019; Vlot et al., 2017). Recent research indicates PBs reduced BMD and that subsequent cross-sex hormone treatment did not compensate for this loss of bone density (Roy et al., 2024; Sanna et al., 2024). No studies examined how the duration of PBs impacts bone health, underscoring the need for further research (Lee et al., 2020).

The CPS-PS discounted concern regarding the effects of PBs on cognitive development, stating that “concerns voiced by opponents of gender-affirming medical care around the potentially permanent impacts on cognitive function … have not been substantiated” (Vandermorris & Metzger, 2023, p. 441). While this may technically be true, as the field of pediatric gender medicine is relatively new, it is well established that puberty is a critical period of brain development, with sex hormones playing significant roles (Koolschijn et al., 2014). Disrupting the actions of hormones during puberty may therefore affect cognitive development. This is supported by studies on both non-human animals (Anacker et al., 2020; Hough et al., 2017, 2019) and humans (Schneider et al., 2017; Staphorsius et al., 2015). While Arnoldussen et al. (2022) may give the impression that PBs do not negatively impact cognitive development, as their study found a strong relationship between pretreatment IQ and post-treatment educational achievement, the methodological design, particularly the lack of post-treatment IQ assessments and evaluation of executive functions (which in particular develop into adolescence and beyond), precludes definitive conclusions (Ferguson et al., 2021; Tervo-Clemmens et al., 2023). Long-term effects remain unknown, and further research is needed to assess the cognitive impacts of PBs (Baxendale, 2024; Chen et al., 2020).

The long-term effect of puberty suppression during normally timed puberty on adult sexual function remains unknown. In natal males, early use of PBs often resulted in an underdeveloped penis, with insufficient tissue to achieve satisfactory depth in a penile inversion vaginoplasty, requiring the use of intestinal tissue—a more complex and risky procedure (van de Grift et al., 2020). Bowers, former president of WPATH and co-author of SOC-8, has publicly stated that she is not aware of any patients who began PBs at Tanner Stage 2 who were able to achieve orgasm after vaginoplasty (Bowers, 2023; Kozlowska et al., 2024). Since most studies of sexual function in transgender people have been of patients who transitioned as adults, little is known about the impact of puberty suppression on orgasmic capacity (Clayton, 2022; Ley, 2021). A retrospective cohort study (van der Meulen et al., 2024) of 37 transfeminine individuals who received PBs between Tanner stages 2 and 5 and vaginoplasty at a mean age of 20.9 years (SD 1.2) found 67% of sexually active participants regularly experienced one or more sexual difficulties such as lack of sexual desire, lack of arousal, difficulty achieving orgasm, premature orgasm, and pain during intercourse. A similar retrospective study (van der Meulen et al., 2025) of 50 transmasculine and 20 transfeminine adults who began puberty suppression before the age of 18 compared outcomes between those who initiated pubertal suppression at early (Tanner stage 2/3) versus late (Tanner stage 4/5) puberty with a cohort of those who initiated medical gender transition as adults and population norms. Sexual dysfunctions such as difficulty initiating sexual contact or achieving orgasm were reported in 58% of transmasculine individuals and 50% of transfeminine individuals. Although the authors suggest that sexual dysfunction and satisfaction were similar across the cohorts, this conclusion is based simply on descriptive statistics; no inferential statistics were conducted. Given the small sample, especially within subgroups, these studies are likely underpowered to detect any differences. Nonetheless, the reported numbers suggest a possible pattern of greater sexual dysfunction among those who began suppression early in puberty. A more rigorous discussion of these studies, their limitations, and their interpretive risks is important to consider (Conway, 2025).

Fertility outcomes differ significantly depending on the treatment path. Research has found that the fertility of children treated with PBs for precocious puberty was not affected, once normal puberty resumes (Bertelloni et al., 2000), but it is not clear that this is the case if puberty is blocked during the normal window for puberty (Stolk et al., 2023). However, those who begin PBs in early puberty and proceed to gender-affirming hormone therapy are likely to be sterile, since PBs halt germ cell maturation required for viable gametes (Bangalore Krishna et al., 2019; Betsi et al., 2024; Stolk et al., 2023). A histology study of orchiectomy specimens found no mature sperm in patients whose puberty had been blocked at Tanner stage 2 or 3 (de Nie et al., 2022). Delaying the initiation of PBs to allow for egg or sperm cryopreservation would mean undergoing many of the physical changes of puberty which PBs are intended to avoid, and, as a result, patients seldom choose this option (Pang et al., 2020). Fertility preservation prior to gamete maturity remains experimental in males, and in females, reproductive success is very limited (Laidlaw et al., 2025).

The systematic review of PBs commissioned by the Cass Review could not draw any reliable conclusions on the effect of PBs on gender-related outcomes, psychological and psychosocial health, cognitive development, or fertility. It found that bone health and height might be compromised (Taylor et al., 2024d). These findings have been confirmed by a more recent systematic review led by methodologists from McMaster University (Miroshnychenko et al., 2025a, 2025b). The Cass Review recommended that PBs should be provided only in the context of a research trial (Cass, 2024b). The National Health Service in the UK has commissioned a clinical trial of PBs which is awaiting regulatory and ethical approval (Feinmann, 2025).

Gender-Affirming Hormone Therapy

The CPS-PS states that “GAHT is considered safe for adolescents, but it can have associated short- and long-term health risks” that “are beyond the scope of this statement” (Vandermorris & Metzger, 2023, p. 442). These risks are important for pediatricians and primary care providers to understand so they can determine if GAHT is appropriate, ensure informed consent, and monitor ongoing health risks.

GAHT is often a life-long commitment. The only study that followed patients from PBs through GAHT to adulthood is the original Dutch cohort study, which did not examine the impact of treatment on physical health (de Vries et al., 2014). More recent studies of adults who have received GAHT have found serious health risks. Tracking of adverse drug reactions from GAHT is complicated by the fact that these medications are prescribed to transgender people off-label, and the risks listed by the drug manufacturer relate to people of the opposite sex to the transgender patient (Gomez-Lumbreras & Villa-Zapata, 2024). Despite the fact that the impacts of GAHT are likely cumulative and may take years to manifest, and few long-term follow-up studies, a growing number of case reports and studies have found associations between GAHT and various morbidities including granulosa cell tumors (Ing et al., 2023; Tumas et al., 2024), invasive breast cancer (de Blok et al., 2019), thyroid cancer (Meci et al., 2025), pelvic floor dysfunction (Silva et al., 2024), and idiopathic intracranial hypertension (Gutkind et al., 2023; Kamboj et al., 2023).

Isolating the effects of GAHT is challenging, as many patients have also received PBs, which may compound health risks. Evidence suggests that combined treatment may increase the risk of metabolic and cardiovascular disease. For example, Klaver et al. (2018) found that patients who took PBs for at least 2 years followed by GAHT for 2–3 years had increased body mass index, high blood pressure, low density lipoprotein and triglycerides and decreased high density lipoprotein and, as adults, higher obesity rates compared to population norms.

A systematic review commissioned by Cass on GAHT found “limited evidence regarding gender dysphoria, body satisfaction, psychosocial and cognitive outcomes, and fertility” (Taylor et al., 2024e, p. 548). While some pre-post studies showed improvements in psychological outcome at a 12-month follow-up, these findings were confounded by concurrent psychological support and psychotropic medications and therefore provided only low certainty evidence. Results for height/growth, bone health, and cardiometabolic effects were inconsistent. Since most studies were of adolescents who had also received PB, the independent effects of GAHT remain unclear (Taylor et al., 2024e). Notably, only those treated with PBs after Tanner stage 4 followed by GAHT were able to produce germ cells regardless of the duration of blockade.

Other systematic reviews and literature reviews have found that the evidence that GAHT leads to improvements in mental health or reductions in suicidality was low or very low certainty and that the observed effect sizes were small with potentially little clinical significance (Baker et al., 2021; Christensen et al., 2023; Ludvigsson et al., 2023; McDeavitt, 2024; National Institute for Health & Care Excellence, 2020; Thompson et al., 2023; Zepf et al., 2024). One systematic review and meta-analysis, however, found strong evidence that transgender people were at higher risk of cardiovascular disease compared to cis-gender people of the same birth sex (Van Zijverden et al., 2024), including an increased risk of stroke, myocardial infarction, and venous thromboembolism. These findings were confirmed by another recent systematic review of GAHT for those under the age of 26, which found high certainty evidence for cardiovascular events in transmen treated with testosterone and very low certainty evidence for improvement in gender dysphoria, global function, and depression. The evidence with regard to bone mineral density and sexual dysfunction was also very low certainty (Miroshnychenko et al., 2025a, 2025b).

A recent systematic review of GAHT on patient-reported outcomes in Canada highlighted the “need to improve standardization of outcome measurement for gender-affirming hormone treatments in order to improve the robustness of the evidence base, thereby contributing to higher quality research and evidence-informed clinical practice” (Jackman et al., 2025). The Cass Review found that the evidence base for psychological benefit from hormones was weak. While the option to provide hormones from age 16 remains available in England, the Cass Review recommended “an extremely cautious clinical approach, a strong clinical rationale for providing hormones before the age of 18” and that “every case considered for medical treatment be discussed at a national Multi-Disciplinary Team” (Cass, 2024b, p. 197).

Informed Consent

The CPS-PS did not discuss informed consent. Under Canadian law (except Quebec, which has a minimum consent age of 14), there is no minimum age for medical consent. Instead, physicians must assess a minor’s capacity on a case-by-case basis to determine whether a child understands the nature and consequences of the proposed treatments (Coughlin, 2018). WPATH SOC-8, which the CPS-PS relied on, had no age restrictions except for a recommended minimum age of 18 for phalloplasty (Coleman et al., 2022).

Concerns about youths’ capability to provide informed consent for GAC are grounded in both developmental science and ethical analysis. It is well documented that the prefrontal cortex, integral for rational decision-making and impulse control (i.e., executive functions), is among the last to mature, leaving adolescence a period of heightened vulnerability to high risk-taking and social pressure (Arain et al., 2013; Casey et al., 2008; Committee on Bio-ethics et al., 2016; Ferguson et al., 2021; Smith et al., 2014; Steinberg et al., 2008; Tervo-Clemmens et al., 2023). It is also generally understood that identity continues to develop and evolve into adulthood (Kroger, 2017) and that adolescence is a crucial stage of identity exploration and development (Erikson, 1968; Marcia et al., 1993; Sokol, 2009). Research suggests the clarity with which individuals perceive their future selves plays a significant role in decision-making. When individuals feel a strong sense of connection to their future selves, they are more likely to make better-informed decisions, prioritizing long-term health and well-being over immediate gratification (Rutchick et al., 2018; Yang et al., 2024).

Given the ongoing development of executive functions and identity during adolescence, GAC presents a complex ethical landscape. Young people are required to make decisions about treatments which have a high degree of uncertainty and potential life-long consequences on fertility, sexual function, bone density, and general health as well as on social life and intimate relationships at an age when their identity and cognitive decision-making capacity have not fully developed—a period when they may be least able to weigh potential risks and benefits. Informed consent requires that the patient has capacity to consent, understand the nature and consequences of the treatment and any alternative treatments including no treatment, and be free of coercion (Brunskell-Evans, 2019, 2020; Canadian Medical Protective Association, 2022). Schachter et al. (2005) noted that informed consent requires both understanding and appreciating the relevant information. They noted that adolescents’ ability to think abstractly and foresee consequences of treatment choices (i.e., executive function) is likely evolving and that adolescents may therefore lack the necessary maturity to sufficiently appreciate treatment decisions necessary to give informed consent.

Vrouenraets et al. (2020) underscored the moral dilemma that arises when there are doubts about the adolescent's ability to comprehend the life-long implications of gender-affirming medical treatments. The dilemma is complicated by the uncertain long-term effects of pubertal suppression, the fact that the treatment is done on a still-developing healthy body, that the young person involved is likely not psychologically or cognitively mature, and the potential negative effects on “physical development, brain growth and the building of a consistent gender identity.” In another study, Vrouenraets et al. (2021) found that 93.2% of patients under the reference standard and 89.2% under the MacArthur Competence Assessment Tool-Treatment (MacCAT-T) were competent to consent to PBs. However, as Levine et al. (2022) argued, the MacCAT-T tool was designed and validated to assess medical consent capacities of adults (not children) suffering from serious mental health conditions, and did not account for how lack of life experience could affect a young person’s ability to comprehend the significance of loss of sexual function and fertility. A subsequent study by Vrouenraets et al. (2022) also raised concerns about the ability of children and adolescents to appreciate the long-term consequences of gender-affirming treatments. This study also highlighted challenges such as the lack of standardized methods for assessing medical decision-making competence and the undue influence of parents on the child’s decision-making. In both of the Vrouenraets et al. studies, all the clinicians, patients, and parents assumed that PBs were largely reversible.

In a WPATH panel discussion, Metzger, a co-author of the CPS-PS, acknowledged that 14-year-olds are unable to understand the impact of loss of fertility and discussing fertility preservation was like talking to a “blank wall” (Hughes, 2024, p. 12), calling into question whether these young people have sufficient understanding of the long-term effects of PBs and GAHT to provide informed consent.

Patients should be made aware of the evidence that gender dysphoria can resolve without treatment and the low certainty of evidence that gender-affirming treatments are beneficial (Levine et al., 2022). While informed consent is often dealt with as a staged process, with the child patient and/or parents being asked for consent separately at each step, in practice the distinction between the stages is often blurred. Starting PBs is associated with a greatly increased probability of proceeding to GAHT which, in turn, leads to an increased probability of surgeries. Fully informed consent requires that the patient understand the ramifications of the entire gender transition process before commencing the first step (Pilgrim & Entwistle, 2020; Steensma et al., 2017). Physicians providing gender-affirming services, therefore, must understand this to engage in shared decision-making.

Patient and family goals, values, and preferences are shaped by the information they receive. In Canada, it is unclear whether patients consistently receive balanced comprehensive information about GAC. Without a full understanding of the medical concepts, risks, benefits, and alternatives, preferences may be misinformed. Moreover, an affirming approach, by its nature, may discourage exploration of underlying causes of gender distress, thereby potentially limiting critical insights and compromising patient autonomy (Sinai & Sim, 2024).

While informed consent is essential to uphold patient autonomy, informed consent alone does not determine the ethical appropriateness of a treatment. Physicians must also consider and weigh the ethical principles of beneficence, non-maleficence, and justice. Ethical practice requires evidence that a proposed intervention offers a potentially positive benefit–harm ratio before consent is relevant (Goodman & Houk, 2022). Currently, this is not the case with gender-affirming medical treatments. As Kingdon et al. (2025) rightly point out, prioritizing autonomy over patient welfare is a departure from well-established bioethical norms (Beauchamp & Childress, 2019). Autonomy does not supersede all other bioethical principles, but must be balanced against the physician’s duty to safeguard the patient’s best interests and right to an open future (Jorgensen et al., 2024; Surendran et al., 2025). There remains great uncertainty in pediatric gender medicine regarding diagnostic reliability and scientific evidence. Autonomy alone, in such cases, cannot ethically justify a treatment that may potentially compromise long-term welfare.

Conclusions

The rights-based affirmation approach for the treatment of gender dysphoria promoted by the CPS-PS is being replaced globally by an evidence-based approach prioritizing non-maleficence and beneficence (Kozlowska et al., 2024), and a neutral psychological exploration rather than immediate affirmation (Hutchinson, 2025; Levine, 2021; Radobuljac et al., 2024). Countries adopting an evidence-based approach include Finland (Council for Choices in Healthcare in Finland, 2020), Sweden (The Swedish National Board of Health & Welfare, 2022), Norway (UKOM, 2023), the UK (NHS England, 2024), New Zealand (Ministry of Health, 2024a, 2024b), Italy (Italian National Bioethics Committee, 2024), and the USA (Department of Health & Human Services, 2025).

Recent developments in psychotherapeutic practice further underscore a shift in the care of gender-distressed youth (Radobuljac et al., 2024). Other jurisdictions are adopting practices grounded in the Cass Review’s recommendations, emphasizing holistic assessment, individualized formulation, and developmentally appropriate care, which reconnects the field with the practice of child and adolescent mental health thereby rejecting the exceptionalization of gender dysphoria that has occurred in recent years. Unlike the affirmation approach of the CPS-PS, psychotherapy for gender-distressed youth informed by the Cass Review recognizes the complexity of identity development, including gender identity, and the need for supportive exploration without foreclosing outcomes (Hutchinson, 2025). While one may argue that the evidence for psychotherapy for gender dysphoria is also likely low certainty, prudent ethical principles recognize that when two interventions are associated with similar certainty of evidence, but one carries a lower risk of harm, a strong recommendation may be made in favor of the safer option (Chong et al., 2023). Meanwhile, the Canadian Pediatric Society continues to uncritically promote the gender-affirming model despite, in other contexts, calling for major reform to improve the safety and efficacy of medications prescribed to Canadian children and despite acknowledging that Canada can learn from the European Union regarding pediatric medicine and research (Hepburn et al., 2019). A recent paper published in Paediatrics and Child Health (Kadoura et al., 2025) provides case presentations and “learning points” for general pediatricians on how to treat gender-distressed youth. The article refers readers to the CPS-PS and resources created by various Canadian gender clinics and groups focused on a rights-based model. Unfortunately, it does not mention the Cass Review, any systematic reviews of the evidence, the debate on how best to care for these youth, or any international developments.

The UK and other jurisdictions have taken steps to safeguard its youth. Canadian gender-distressed youth deserve the same standard of care. As the Editor in Chief of the British Medical Journal pointed out, “the Cass review is an opportunity to pause, recalibrate, and place evidence-informed care at the heart of gender medicine. It is an opportunity not to be missed for the sake of the health of children and young people” (Abbasi, 2024).

Author Contributions

All authors have read and have approved the Letter.

Funding

Open Access fees were provided by the Society for Evidence-Based Gender Medicine (SEGM). SEGM only provided Open Access and had no other role in this work including review of the manuscript before submission.

Availability of Data and Material

(Data transparency): The Letter contains no data.

Code Availability

(Software application or custom code): The Letter contains no code.

Declarations

Conflict of interest

All authors declare no conflict of interest.