CAN-SG submission to NHS England Interim Clinical Policy: Puberty Suppressing Hormones for Children and Adolescents who have Gender Incongruence/Dysphoria

The Clinical Advisory Network on Sex and Gender has contributed to NHS England’s consultation on puberty suppressing hormones, and welcomes the proposal to stop the routine prescription of puberty suppressing hormones (PSH) to children and young people with gender dysphoria or gender incongruence and to offer psychological approaches instead.

We still however have concerns, both about the proposal to offer PSH as part of research, and the exceptions to the policy which would allow the continued use of PSH outside research conditions.

NHS England is consulting until 1 November 2023 on its interim policy on puberty suppressing hormones (PSH), otherwise known as puberty blockers.

The Clinical Advisory Network on Sex and Gender welcomes the proposal to stop the routine prescription of puberty suppressing hormones (PSH) to children and young people with gender dysphoria or gender incongruence and to offer psychological approaches instead.

Nevertheless we have several serious concerns, both about the proposal to offer PSH as part of research, and the exceptions to the policy which would allow the continued use of PSH outside research conditions.

The NICE systematic review found “very low certainty” evidence of benefit or harm, meaning that we do not know whether Puberty Suppressing Hormones are effective or safe when used to treat gender dysphoria. This underpins the proposed policy which is to no longer routinely offer PSH to children and young people with gender dysphoria, but it also underpins the proposal to do more research on PSH in this group. Information about the proposed research is contained in the health inequalities impact assessment section where it says that prospective research is being planned on use of PSH in “early onset” gender dysphoria.

We are concerned about the prospective interventional research on PSH and think that if wider evidence of harm had been taken into account there would be more caution about proposing prospective research on PSH. We believe there are safer, more ethical and potentially more informative avenues of research.

The consultation has three questions about the proposed policy:

Question 3 Has all the relevant evidence been taken into account?

We would like to comment on the limitations of the research evidence. We also think there is some more evidence that could be taken into account.

NICE systematic review lacked a clear conceptual framework and did not evaluate rationale and aims of treatment with Puberty Suppressing Hormones (PSH)

The use of PSH in gender dysphoria does not have a clear clinical aim, and this is not addressed by the NICE systematic review (National Institute for Health and Care Excellence 2020) or the Interim Clinical Policy on PSH. As stated in the Cass Interim Review (Cass 2022), there is a lack of conceptual agreement about the meaning of gender dysphoria. Treatment is even proposed by some based on “gender identity” (which also has a lack of conceptual agreement) without the presence of distress or gender dysphoria, an approach which is unevidenced and in our view completely unjustified.

The interim PSH policy background document attempts to explain why PSH have been used as treatment for gender dysphoria/incongruence, but fails to give a coherent rationale. The document starts with explaining gender dysphoria/incongruence as a

“condition where a person experiences discomfort or distress that is caused by a discrepancy between a person’s gender
identity (how they see themselves regarding their gender) and that person’s natal sex (and the associated gender role, and/or primary and secondary sex characteristics)”

The document then acknowledges that gender is a social construct by citing the WHO definition of gender.

“Gender refers to the roles, behaviours, activities, attributes and opportunities that any society considers appropriate for girls and boys, and women and men.”

WHO website Health Topics: Gender, at

There is no explanation of gender identity that does not involve reference to social constructs.The document provides no evidence that gender identity exists as something innate, unchanging and uninfluenced by society (despite acknowledging that gender is a social construct), and it provides no rationale for why if there is a mismatch between one’s gender identity and one’s sex it is the body that should be altered by medication.

The NICE review does not address the question as to why suppressing puberty would be a preferred option for managing psychosocial distress and improving well-being in this cohort when there are other interventions with a better established safety profile.

We believe the evidence review should have gone back and reviewed the evidence for PSH from when they were first proposed as a treatment for gender dysphoria, in the process elucidating the nature and aetiology of the condition being treated, its natural history, the rationale for using PSH, and the intended outcomes.

Changing aims of treatment

According to the Cass Interim Review, the PICO (population, intervention, control, and outcomes) on which the systematic review was based lacked a definition of the intended outcomes of puberty blockers and suitable comparators for the intervention.

This reflects the uncertainty, lack of clarity and changing nature of the objectives of treatment with PSH, which would impact an assessment of the evidence. The clinicians who developed the Dutch protocol theorised that by stopping puberty, this would make subsequent ability to “pass” as the opposite sex easier following cross-sex hormones and surgery, and that PSH would allow a “pause” in pubertal development to give the young person time to think about their gender identity (Delemarre-van de Waal & Cohen-Kettenis, 2006). These were the explicit justifications by those who pioneered PSH use, yet the NICE systematic review did not address research on whether or not these aims were achieved or were beneficial. The aim of “passing” better no longer seems to be an aim of treatment with PSH, and there is no evidence that PSH provide a “pause” that gives young people “time to think” as nearly all of children given PSH go on to gender affirming hormones. These aims of the original Dutch pioneers that provided the rationale for PSH use in the UK were not considered by NICE.

Instead the NICE review looked at the impact on gender dysphoria, mental health, quality of life, and body image. They found only “very low certainty” evidence. It is worth asking why these were the outcomes under consideration in the first place, given that it is known that they are factors which, in adolescence, may fluctuate considerably over time even without intervention and may change due to social factors. Given the subjective nature of these outcomes, one might expect a significant placebo effect from any intervention.

Diagnostic categories should be reviewed

Research on any condition requires valid and stable diagnostic categories. We do not believe the current diagnostic categories serve that purpose. We urge NHSE to review the development of the diagnosis of ‘Gender Dysphoria’ (DSM-V) and ‘Gender Incongruence’ (ICD-11). The definitions and descriptions of gender identity disorders have changed significantly over the years. From our perspective, they do not support what we are seeing in our practice, and the difficulties with research and clinical practice in this area are amplified by the way ICD and DSM have taken up an ideologically driven understanding of these disorders/identities which have led to the diagnostic categories that we are now obliged to work with. We would recommend that these diagnostic categories be re-examined, and that this be done with the input of a range of clinical perspectives.

For those reasons, we suggest that a review of the literature that led to the use of PSH, including the original Dutch protocol and associated literature, focusing on the conceptual framework used by the clinicians and researchers, would be very useful to better understand the original assumptions and aims, and how these might now have changed.

Evidence from Swedish systematic review

Since the publication of the NICE systematic review, Sweden conducted a systematic review (Ludvigsson et al, 2023) that led to a change in policy on use of puberty suppressing hormones, involving restricting access to PSH to a research context only.

The Swedish researchers assessed more than 9900 abstracts  from fifteen scientific databases and identified 24 relevant studies. They focused on psychosocial effects, bone health, body  composition and metabolism, and therapy persistence in children (<18  years of age) with gender dysphoria undergoing treatment with gonadotropin-releasing hormone analogues (GnRHa).

It would have been helpful to have included the Swedish systematic review in the updated evidence review for comparison and to ensure all primary studies were included. 

Failure to consider animal studies on brain development

When considering novel treatments, it is usual to start with animal studies of safety, in particular where the treatment has major effects. No animal studies are cited in the systematic reviews, despite the fact that several studies have demonstrated harmful effects on the adolescent animal brain which are relevant to one of the greatest risks that PSH may carry – that of harmful effects on the developing adolescent human brain. We think that relevant animal studies should be considered.

The hormones used to suppress puberty are Gonadotrophin Releasing Hormone Agonist (GnRHa). Experimental studies on the physiological impacts of GnRHa have been conducted in 17 species of animals. Eleven studies have reported the impact of pharmacological puberty suppression with GnRHa on indices of behavioral function in the animal. The behavioural and cognitive measures used in these animal studies can be broadly divided into three categories:

  1. Interactions with the environment
  2. Responses to stress
  3. Performance on cognitive tasks.

The results from these studies indicate that treatment with GnRHa has a detrimental impact on learning and the development of social behaviours and responses to stress in mammals. Sex-specific effects were observed in multiple studies (Anacker et al., 2021; Nuruddin, Krogenaes, et al., 2013; Wojniusz et al., 2013).

Significant effects of treatment were also evident on measures of brain structure including overall volume (Godfrey et al., 2023), functional connectivity (Pincus et al., 2021), and neuronal density (Anacker et al., 2021). The results from these studies are generally consistent and indicate that the suppression of puberty impacts brain structure and the development of social and cognitive functions in mammals, but the impacts are complex and often sex-specific consistent with the MRI evidence of sex-specific differences in neurodevelopment in human adolescence (Giedd et al., 2012). There is no evidence in the animal literature that these effects are reversible following discontinuation of treatment (Hough et al).

In a single case study, Schneider et al. (2017) examined the impact of pubertal suppression on brain white matter and cognitive function in an 11-year-old treated for gender dysphoria (male-to-female). On admission, at the age of 11 years and 10 months, the patient was assessed to have a global IQ of 80. Treatment with GnRHa was instigated at age 11 years, 11 months. The patient was reassessed age 13 and 3 months, at which time, a loss of 9 IQ points had occurred, and the IQ had dropped to 71. A loss of 15 points was evident in working memory. At 14 years and 2 months, a loss of 10 global IQ points and 9 points in working memory remained apparent. The verbal comprehension index (a measure that depends on the expansion of vocabulary and conceptual thinking in adolescence, for the standardized score to remain stable) deteriorated progressively over the follow-up, falling from the initial baseline of 101 to 91 (age 13) and 86 (age 14), a loss of 15 points over 3 years (Schneider et al., 2017).

Other evidence of harm from puberty suppressing hormones

We also think that research evidence of PSH harms from treatment of precocious puberty should be considered, such as reduced IQ (Hayes, 2016 and Mul, 2001). PSH has also been used to delay normally timed puberty in children of short stature with the intention of increasing adult height but studies have warned of reduced bone density outweighing benefit (Yanovski et al., 2003). Research from GnRHa use in prostate cancer has highlighted the risk of diabetes and cardiovascular events (Keating et al., 2006). GnRHa use as “antilibidinal medication” in sex offenders has yielded evidence of osteoporosis, increased risk of diabetes and cardiovascular risk (Giltay and Gooren, 2009), and all these additional sources of information about harms should also be considered.

Evidence for PSH and masculinising/feminising hormones should have been reviewed together.

The NICE systematic reviews looked at evidence for both PSH and gender affirming hormones (masculinising / feminising hormones), and came to similar conclusions about the poor quality of evidence for both.

‘This evidence review found limited evidence for the effectiveness and safety of gender affirming hormones in children and adolescents with gender dysphoria, with all studies being uncontrolled, observational studies, and all outcomes of very low certainty. Any potential benefits of treatment must be weighed against the largely unknown long-term safety profile of these treatments.’

NICE gender affriming hormones evidence review 2020

Given that nearly all children who are given PSH go on to take masculining/feminising hormones and that in practice both PSH and masculining/feminising hormones are part of the same care pathway (either consecutively or concurrently), we think it would have been helpful for the proposed new service to have considered the evidence for them in a combined way, in order to answer the question about whether medical transition overall, with PSH and gender affirming hormones, helps or harms children and young people with gender dysphoria.

Adolescent onset gender dysphoria

The NICE review did not include any evidence about the increasing numbers of young people with adolescent onset gender dysphoria, especially teenage girls, some of whom have been prescribed PSH. If no evidence about this cohort exists then it is vital that it be commissioned. It would be important to know the reason for the 4000% increase in referrals to gender clinics of teenage girls with no history of gender dysphoria prior to puberty, and to study the natural history of gender dysphoria in this cohort.

Question 4 Does the equality and health inequalities impact assessment (EHIA) reflect the potential impact that might arise as a result of the proposed changes?

We think the EHIA lacks balance, with too much emphasis on the potential negative effect of the policy of no longer routinely prescribing PSH, and not enough recognition of the potential positive effects of no longer routinely prescribing PSH. This over-emphasis on potential negative effects of PSH no longer being routinely available could inadvertently lead to pressure on clinicians to allow more “exceptions” to the policy. Given the risk of harm from PSH and the lack of evidence of benefit, the proposed policy to no longer routinely prescribe may well have a beneficial protective effect on the children and young people who would otherwise have been administered PSH, including vulnerable groups: teenage girls, children in care, children with neurodiversity, children with mental health problems, and children and young people with emergent same-sex sexual orientation. There should be more balance in the EIA and more recognition of the benefits to these groups of being protected from potential harm.

Children and Young People’s Gender Dysphoria
Research Oversight Board

It is odd that the information that the proposed research on PSH will be on early onset gender dysphoria is located in the EHIA and not in the interim policy consultation document. Its location in the EHIA means it is likely to be missed, yet it is important.

The EHIA says that the Oversight Board has approved the
development of a study into the impact of GnRHa on gender dysphoria in children and young people with early-onset gender
dysphoria, and that the definition of ‘early onset’ and ‘late onset’ will be developed by the clinical study team in due course. There is no explanation for why this distinction was made or why the “early onset” group was chosen as the focus of research. This group is already known to have a high level of natural resolution of gender dysphoria once they have gone through puberty, many being boys who grow up as same sex attracted (Singh et al, 2021). It is important that the research oversight board takes account of this and recognises the risks of PSH to those with an emergent same sex orientation. We go back to the points we made at the beginning of our contribution which is that any research on use of PSH first has to elucidate the nature and aetiology of the condition being treated, the natural history without intervention, the rationale for using PSH, and the expected outcomes.

Question 5: Are there any changes or additions you think need to be made to this policy?

Overall, CAN-SG members welcome the decision that puberty blockers will not be available for routine treatment due to a lack of evidence on safety and effectiveness, and that the  primary intervention will focus on psychological approaches.

However, CAN-SG members have several concerns about the proposal to continue providing access to PSH to children and young people with gender incongruence/dysphoria, either as part of research or as one of several exceptions within the policy.

The NICE evidence review assessed the evidence for the risks and benefits of PSH as “very low certainty” using modified GRADE. This means that we do not know whether Puberty Suppressing Hormones are effective or safe when used to treat gender dysphoria.

The NHSE proposal on puberty-suppressing hormones (PSH) aims to protect children and young people from harm by advocating for less invasive treatments until more is known about the risks and benefits of PSH.

Given the above, we are concerned that the unevidenced and potentially harmful use of PSH will continue in several situations. Depending on various conditions, this could amount to continued substantial use of PSH in a context where there are serious concerns about safety and efficacy. We believe the PSH prescribing policy should explicitly address these concerns.

The situations where PSH will continue to be prescribed include:
  1. As part of research
  2. In exceptional cases
  3. Continuing prescriptions for those already taking PSH
  4. For those who have already been referred to an endocrinologist but not yet started PSH
  5. For those for whom PSH is a precursor to masculine/feminine hormones
  6. For those receiving PSH from private sources
Prescribing PSH as Part of Research
Prescribing PSH in a research setting means that children and young people will be experimental subjects in an intervention with profound effects on physical, psychological, and developmental processes, about which little is known. Puberty involves sexual maturation, brain and cognitive development, social and personality development, as well as physical development.

We recognise that the question of whether or not the benefits of PSH in children with gender dysphoria outweigh the risks is a difficult research challenge. We think that the main reason we are facing this problem is that the proponents of this intervention have repeatedly avoided doing comparative research, often leveraging the circular argument that preventing some children from having access to this unproven treatment in a comparative trial is unethical (Biggs 2023). Given the fact that these drugs have been in widespread use for some time now in several countries, it is tempting to regard them as a ‘standard’ treatment despite the lack of any good evidence of their efficacy and safety. This would be wrong. We should use an evidence based approach for the efficacy and safety of this intervention just as we would for any other intervention.

CAN-SG believes that the grounds that might justify prospective research in which children and adolescents are given PSH have not been established for the following reasons:

  1. There is a dispute regarding the causes and natural history of gender dysphoria, and reasonable concern that epidemiological trends indicate that social contagion is a driver for at least some cases (Hutchinson A., 2020; Sinai J., 2022). Given these disputes, a trial of an invasive intervention like PSH is premature.
  2. There is no clear scientific rationale for puberty suppression leading to better health outcomes in children with gender dysphoria, so it is not clear what benefit such a trial would be looking to measure.
  3. There is some evidence of harm when PSH is given in this context, and there is further theoretical risk based on human and animal data.
  4. It is highly doubtful that children could give informed consent to such an intervention, which could lead to loss of fertility and sexual function. In a trial context, parents would be expected to consent to treatment knowing these possible risks. This has significant ethical implications. It also raises child safeguarding concerns.

Crucially, although estimates vary between cohorts, and a small study shows a correlation with the “intensity” of gender dysphoria in childhood and persistence (Steensma 2013), there is evidence that most children with gender dysphoria experience spontaneous resolution of their symptoms by late adolescence/early adulthood. There is no reliable way to discern which children will or will not desist (Zucker 2018).

The fact that 96%–98% of children who undergo puberty suppression continue to cross-sex hormones and other interventions (Brik et al., 2020; Carmichael et al., 2021; Wiepjes et al., 2018) strongly suggests that puberty itself is important in bringing about the resolution of gender dysphoria for some (perhaps most) children who experience it. It is therefore possible that puberty suppression promotes persistence of gender dysphoria and increases the likelihood that children will go on to seek yet more invasive and risky medical and surgical interventions in adulthood.

In this context, it seems unlikely that it would ever be ethically sound to conduct a prospective trial. As we don’t know which children, if any, are likely to benefit, such a trial would knowingly expose many children to potentially harmful intervention that would be of no benefit to them.

Other areas of research that could inform policy

We propose that research on the use of puberty suppression hormone (PSH) for gender dysphoria should consist of retrospective observational studies looking at patients who have already received PSH, as well as the natural history of gender dysphoria in those who did not receive medical intervention. Notwithstanding the limitations of retrospective non-comparative studies, every effort should be made to gather data from previous cohorts, in the UK and internationally, and these should be carefully analysed before any prospective study is contemplated.  It is paramount that clear hypotheses regarding the aim of treatment and potential benefits of PSH are formulated, and that these are revisited in the light of all available retrospective data.

There should also be research into the new and very large cohort of young people, mainly teenage girls, presenting to gender clinics in adolescence to elucidate the contributions of comorbidities and social contagion to this phenomenon, and to what extent gender dysphoria spontaneously remits in adolescents who have not presented with gender incongruent behaviour in childhood.

In recent years, detransitioners have become more visible and vocal about their experiences with medical interventions (Irwig 2022; Littmann 2021). We believe that carefully designed and compassionately conducted research into detransitioners’ experiences and health outcomes, as well as the experiences and outcomes of those who remain trans-identified, should be a priority and should inform policy decisions in a timely manner.

There should be long term follow up and analysis of outcomes (physical, psychological and social) for all children and young people referred to gender clinics, now and in the past, both those who received PSH and masculinising/feminising hormones, and those who did not. It would be useful to review the evidence and do further research on the natural history of gender dysphoria in the “early onset” group of children with gender dysphoria, which predominantly affects boys, especially as it is being proposed to conduct prospective interventional research in this group.

As said in response to Question 3 it would have been helpful to have considered the evidence and consulted on the policy on masculinising/feminising hormones at the same time as the consultation on PSH because, in practice, they go together and there are similar concerns about lack of evidence of benefit, and about irreversibility, risks and long term effects.

Finally, there are now many clinicians from diverse training backgrounds working with children and adults who have experienced gender dysphoria.

As many of our members know from firsthand experience, this field is subject to extraordinary clinical, cultural, and political challenges.

We would support research that sought a diverse range of views from clinicians in this field to understand clinical decision-making and identify areas of clinical equipoise.

Prescribing PSH outside of research

We don’t think initiating or continuing PSH prescription in the other groups (2-6 listed above) is justified because these children and young people should be equal beneficiaries of the caution that has led to the decision to restrict PSH to research settings only.

Not only will children and young people continue to be subject to potentially harmful treatments with no known benefit, but also, being outside of a research setting, they will not contribute to the collective improvement in knowledge about the use of PSH, which is the only possible justification for using them.

Exceptional cases

It is difficult to see what would qualify as an exceptional case of gender dysphoria sufficient to justify giving an unevidenced and potentially harmful drug. No examples of what would count as an exception have been given. Whatever the exception, one can be sure it would act as a precedent for others to claim that they too have exceptional status, and this could undermine the whole idea of only giving PSH as part of a research program.

It is especially concerning that the interim policy proposal states that while there is no research planned on use of PSH in what it calls (without definition) “late onset gender dysphoria” such young people may still be prescribed PSH under “exceptional circumstances.” Given that the PSH policy endeavours to be evidence based we think it is contradictory to envisage any cirumstances where it may be appropriate to prescribe PSH to the group about which there is even less reliable research than there is for the “early onset” cohort. This is the group that includes the rapidly increasing cohort of adolescent girls presenting to gender clinics with puberty onset gender dysphoria, about whom almost nothing is known.

We think there should be no exceptions.

Continuing or initiating PSH for those already being prescribed or referred to endocrinology

Given the concerns and lack of evidence for PSH it would expose children to continuing risk with no known benefit to continue to prescribe or initiate these. Those already on PSH should have their treatment reviewed and only continued under the same conditions as any child where PSH is being considered. This would also apply to those who have not yet started PSH, but who have been referred to an endocrinologist. Just because a child has already been referred to an endocrinologist is no reason not to provide them with the protection of the proposed policy. It should not be the decision of an endocrinologist to give these children PSH. Instead any proposal to prescribe them PSH should be under the same conditions as for all other children where PSH is being considered, and the first line of treatment shouild be psychological support .

PSH as a precursor or co-prescription with masculinising/feminising hormones

The statement in the consultation document that

“puberty-suppressing hormones may be considered for some individuals to suppress puberty to be followed later with gender-affirming hormones and possibly gender-affirming surgery from the age of 18”

is very concerning. This use of PSH would apply to children or young people aged 16 and 17, and possibly as young as 15, depending on the policy for gender affirming hormones (not yet published).

Giving PSH as a precursor or co-prescription with masculinizing or feminizing hormones (referred to in the NICE evidence review as gender affirming hormones) also carries risks and lacks evidence of benefit. The NICE evidence review (NICE 2020) of gender affirming hormones for children and adolescents with gender dysphoria, which informed the Cass interim review, concluded:

‘This evidence review found limited evidence for the effectiveness and safety of gender affirming hormones in children and adolescents with gender dysphoria, with all studies being uncontrolled, observational studies, and all outcomes of very low certainty. Any potential benefits of treatment must be weighed against the largely unknown long-term safety profile of these treatments.’

NICE Evidence Review 2020

PSH use in conjunction with masculinising/feminising hormones should be subject to the same constraints and caution as PSH used alone. 

Failure to publish gender affirming hormone policy

A clinical policy on gender affirming hormones or masculinising/feminising hormones, and the use of PSH as a precursor to to those hormones, is referred to in the draft clinical policy on PSH.

A gender affirming hormone policy is also referred to in NHS England’s Interim Service Specification for Specialist Gender Incongruence Services for Children and Young People (NHS England 2023). The service specification states that the approach for onward referrals to endocrinology clinics are described in separate NHS England clinical commissioning policies for puberty suppressing hormone treatment and gender affirming hormone treatment.

Despite these references to its existence, no clinical policy on gender affirming hormones has been published.

It is clear that policies on PSH and on gender affirming hormones cannot be considered in isolation, given the way that they are inter-related and used together in practice. If a policy on gender affirming hormones does exist it should have been published and consulted on with the PSH consultation.

Private prescribing of PSH

All NHSE commissioning policies should include child safeguarding concerns and we believe this policy is no exception. For that reason we believe NHSE should raise the issue of private prescribing with the appropriate authorities, with a view to legislation to ban this. The EHIA recognises that one risk from the proposed PSH policy is that more children and young people may try to obtain PSH from private sources. The risk of harm with unregulated use of PSH is so significant as to amount to self-harm if initiated by the child or child abuse if initiated or supported by others. Although private prescribing is not explicitly part of this consultation, we don’t think it should be ignored by those with responsibility for the health and safety of children and young people, including NHSE.

Comments on background consultation document

Language and definition of concepts

The background statement in the draft policy states that, “it is likely that the development of gender identity is multifactorial and influenced by both biological and social factors.” We think it is important to recognise that gender identity is a contested concept with different meanings used in different contexts. We propose instead, “Children develop an awareness of their sex and of the gender roles and expectations that society imposes depending on sex. It is likely that this process is multifactorial and influenced by both biological and social factors”.

We think the use of the term “assigned gender” is inaccurate, ambiguous, and that it represents gender identity ideology, a belief system, instead of scientific fact.

The consultation document should have been explicit about the meaning of the outcomes in the NICE review being assessed as “very low certainty” using modified GRADE, and explained that this means that we do not know whether Puberty Suppressing Hormones are effective or safe when used to treat gender dysphoria.

Wrong service specification link in consultation document

The consultation document provides a link to the previous service specification for gender services for children and young people published in 2020


and not to the new interim service specification for gender services for children and young people published in 2023.


We think that is an error as it is obvious that the draft PSH clinical policy is related to the new interim service specification, and not the previous one. People should have been able to refer to the new interim service specification when considering the draft PSH clinical policy consultation.


Anacker, C., Sydnor, E., Chen, B. K. et al : (2021). Behavioural and neurobiological effects of GnRH agonist treatment in mice – Potential implications for puberty suppression in transgender individuals. Neuropsychopharmacology, 46(5), 882–890.

Biggs, Michael (2023) The Dutch Protocol for Juvenile Transsexuals: Origins and Evidence, Journal of Sex & Marital Therapy, 49:4, 348-368, DOI: 10.1080/0092623X.2022.2121238

Brik, T., Vrouenraets, L. J. J. J., de Vries, M. C., & Hannema, S. E. (2020). Trajectories of adolescents treated with gonadotropin-releasing hormone analogues for gender dysphoria. Archives of Sexual Behavior, 49, 2611–2618.

Carmichael, P., Butler, G., Masic, U., Cole, T. J., De Stavola, B. L., Davidson, S., Skageberg, E. M., Khadr, S., & Viner, R. (2021). Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK. PLoS One, 16, e0243894. 10.1371/journal.pone.0243894 16 [Crossref] [PubMed], [Google Scholar]

The Cass Review (2022). Independent review of gender identity services for children and young people: Interim report.

Delemarre-van de Waal, H. A., & Cohen-Kettenis, P. T. (2006). Clinical management of gender identity disorder in adolescents: A protocol on psychological and paediatric endocrinology aspects. European Journal of Endocrinology, 155(suppl_1), S131–S137. doi:10.1530/eje.1.02231 [Crossref] [PubMed], [Google Scholar]

Giedd, J. N., Raznahan, A., Mills, K. L., & Lenroot, R. K. (2012). Review: magnetic resonance imaging of male/female differences in human adolescent brain anatomy. Biology of Sex Differences, 3(1), 19.

Giltay EJ, Gooren LJ. Potential side effects of androgen deprivation treatment in sex offenders. J Am Acad Psychiatry Law. 2009;37(1):53-8. PMID: 19297634.

Godfrey, J. R. J., Howell, B. R., Mummert, A., Shi, Y., Styner, M., Wilson, M. E., & Sanchez, M. (2023). Effects of social rank and pubertal delay on brain structure in female rhesus macaques. Psychoneuroendocrinology, 149, 105987.

Hayes, P. (2017). Commentary: Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty. Frontiers in Psychology, 8, 44. doi:10.3389/fpsyg.2017.00044 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]

Hough D, Bellingham M, Haraldsen IR, McLaughlin M, Robinson JE, Solbakk AK, Evans NP. A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep. Psychoneuroendocrinology, 77, 1-8. doi: 10.1016/j.psyneuen.2016.11.029. Epub 2016 Nov 30. PMID: 27987429; PMCID: PMC5333793.

Hutchinson, A., Midgen, M., & Spiliadis, A. (2020). In Support of Research Into Rapid-Onset Gender Dysphoria. Archives of Sexual Behavior, 49(1), 79–80.

Irwig, M. S. (2022). Detransition among transgender and gender diverse people – an increasing and increasingly complex phenomenon. The Journal of Clinical Endocrinology & Metabolism, dgac356.

Keating NL, O’Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006 Sep 20;24(27):4448-56. doi: 10.1200/JCO.2006.06.2497. PMID: 16983113.

Littman, L. (2021). Individuals Treated for Gender Dysphoria with Medical and/or Surgical Transition Who Subsequently Detransitioned: A Survey of 100 Detransitioners. Archives of Sexual Behavior.

Ludvigsson, JF,  Adolfsson, J,  Höistad, M,  Rydelius, P-A,  Kriström, B,  Landén, M.  A systematic review of hormone treatment for children with gender dysphoria and recommendations for research. Acta Paediatr.  2023; 00: 1–14.

Mul D, Versluis-den Bieman HJ, Slijper FM, Oostdijk W, Waelkens JJ, Drop SL. Psychological assessments before and after treatment of early puberty in adopted children. Acta Paediatr. 2001 Sep;90(9):965-71. doi: 10.1080/080352501316978011. PMID: 11683207.

Newhook et al. (2018). International Journal of Transgenderism, 19(2), 231–245.

National Institute for Health and Care Excellence (2020). Evidence Review: Gonadotrophin Releasing Hormone Analogues for Children and Adolescents with Gender Dysphoria. Available from: Nice Evidence Reviews – Cass Review

National Institute for Health and Care Excellence (2020) Evidence Review Gender Affirming Hormones

NHS England 2023 Interim Service Specification for Specialist Gender Incongruence Services for Children and Young People

Nuruddin, S., Krogenaes, A., Brynildsrud, O. B. et al (2013). Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep. Psychoneuroendocrinology, 38(12), 3115–3127.

Pincus, M., Godfrey, J. R., Feczko, E., Earl, E., Miranda-Dominguez, O., Fair, D.,Wilson, M. E., Sanchez, M. M., & Eric;, K. (2021). Chronic psychosocial stress and experimental pubertal delay affect socioemotional behavior and amygdala functional connectivity in adolescent female rhesus macaques. Psychoneuroendocrinology, 127, 105154.

Schneider, M. . A., Spritzer, P. . M., Soll, B. M. . M. B., Fontanari, A. M. . M. V, Carneiro, M., Tovar-Moll, F., Costa, A. . B., Da Silva, D. . C., Schwarz, K., Anes, M., Tramontina, S., & Lobato, M. I. R. (2017). Brain maturation, cognition and voice pattern in a gender dysphoria case under pubertal suppression. Frontiers in Human Neuroscience, 11, 528.

Sinai, J. (2022). Rapid onset gender dysphoria as a distinct clinical phenomenon. The Journal of Pediatrics, S0022347622001858.

Singh D, Bradley SJ, Zucker KJ. A Follow-Up Study of Boys With Gender Identity Disorder. Front Psychiatry. 2021 Mar 29;12:632784. doi: 10.3389/fpsyt.2021.632784. PMID: 33854450; PMCID: PMC8039393.

Steensma, T. D., McGuire, J. K., Kreukels, B. P. C., Beekman, A. J., & Cohen-Kettenis, P. T. (2013). Factors Associated With Desistence and Persistence of Childhood Gender Dysphoria: A Quantitative Follow-Up Study. Journal of the American Academy of Child & Adolescent Psychiatry, 52(6), 582–590.

Wiepjes, C. M., Nota, N. M., de Blok, C. J. M., Klaver, M., de Vries, A. L. C., Wensing-Kruger, S. A., …den Heijer, M. (2018). The Amsterdam cohort of gender dysphoria study (1972–2015): Trends in prevalence, treatment, and regrets. Journal of Sexual Medicine, 15, 582–590. doi:10.1016/j.jsxm.2018.01.016 [Crossref][PubMed][Web of Science ®], [Google Scholar]

Wojniusz, S., Ropstad, E., Evans, N., Robinson, J., Solbakk, A. K., Endestad, T., & Haraldsen, I. R. H. (2013). Sex-specific development of spatial orientation is independent of peripubertal gonadal steroids. PSYCHONEUROENDOCRINOLOGY, 38(9), 1709–1716.

Yanovski JA, Rose SR, Municchi G, Pescovitz OH, Hill SC, Cassorla FG, Cutler GB Jr. Treatment with a luteinizing hormone-releasing hormone agonist in adolescents with short stature. N Engl J Med. 2003 Mar 6;348(10):908-17. doi: 10.1056/NEJMoa013555. PMID: 12621135

Zucker, K. J. (2018). The myth of persistence: Response to “A critical commentary on follow-up studies and ‘desistance’ theories about transgender and gender non-conforming children” by Temple Newhook et al. (2018). International Journal of Transgenderism, 19(2), 231–245.