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Review of evidence for puberty blockers and hormone treatment in youth – Expert Reaction

The BMJ has today released four systematic reviews of clinical guidelines and available research on puberty blockers and hormone treatment for gender transition in children and adolescents, published in the Archives of Disease in Childhood.

The reviews were commissioned to inform the Cass Review, an independent report and recommendations on specialist services for young people with gender dysphoria in the UK, also published today.

The review of 23 clinical guidelines included clinical guidelines from New Zealand.

The research is available here: reviews of puberty blockers, hormone treatment, and clinical guidelines (part 1 and part 2).

The SMC asked third-party experts to comment.

Dr Ben Albert, Paediatric Endocrinologist,Starship Children’s Health, Te Whatu Ora, and Senior Research Fellow, Liggins Institute, University of Auckland, comments:

“The BMJ published a series of papers on the care of young people with gender dysphoria, people who do not feel right with the gender they were born into. This can cause severe distress and young people with gender dysphoria need support. Care for these young people often involves assessment by a multidisciplinary team and may include puberty blockers and hormonal treatments to affirm the gender felt by the young person.

“These reports found that the quality of evidence supporting the use of these treatments, or guidelines for gender dysphoria were poor. There is consensus that these young people need the support of a multidisciplinary team, but whether puberty blockers and hormone treatments improve mental health, body satisfaction and wellbeing has not been established. Puberty blockers used in adolescence can limit the strengthening of bones that occurs at this age.

“This research reminds us that we don’t have strong evidence that the treatments provided for young people with gender dysphoria are helpful. There is a need for high-quality research to understand this better. In the meantime, support should be provided in a multidisciplinary team, and decision making made with young people must acknowledge the uncertainty that treatments are truly beneficial.”

Conflicts of interest: None

Dr Rona Carroll, General Practitioner and Senior Lecturer, University of Otago, comments:

“An individualised and holistic approach to caring for and supporting children and young people who are gender diverse has long been the approach in Aotearoa. When medications are used, these are carefully considered, weighing up risks and benefits with the young person, their whānau and health professionals from different disciplines.

“The reports published today in the UK reflect the challenges and ethical considerations of conducting randomised controlled trials in this field, and the longstanding underfunding of trans health research more generally. In this context it is not uncommon for medical guidelines to utilise available research, together with clinical experience and expert consensus, based on local and international approaches to care. The majority of evidence presented in most medical guidelines would not be classed as high quality, this is not unique to transgender healthcare.

“Whilst more longitudinal research is needed, the evidence that does exist points to improved wellbeing when gender affirming medications are used in line with current guidance, and distress when gender affirming healthcare is restricted. Funding for further research specific to Aotearoa would be welcomed. The report published today again shows how the UK is an outlier in this field, and that our practice in Aotearoa aligns with other countries such as Australia and Canada.”

Conflicts of interest statement: “I am a member of the PATHA executive committee and a trans health researcher. One of the authors of the NZ Guidelines is my husband in his role as an endocrinologist. I am not aware of other conflicts.” *

Dr Paul Skirrow, Clinical Psychologist and Neuropsychologist, Strategic Advisor the New Zealand College of Clinical Psychologists, comments:

“We would urge the public to interpret the findings of these reviews with some caution – many people will assume that this research suggests that puberty blockers and hormone treatments should never be offered, which would be mistaken.

“The authors ultimately conclude that: ‘No conclusions can be drawn [about the effect of puberty blockers].’ This research highlights that we currently do not know how effective these treatments are, or who they are most effective with, but there are many reports of benefit from the people who use them and clinicians who provide them. What research we do have, albeit of limited quality at present, appears to suggest there may be benefits overall- however, we do not currently know who specifically is likely to benefit.

“With regard to hormone treatments, the authors do conclude that ‘There is suggestive evidence from mainly pre–post studies that hormone treatment may improve psychological health.’ However, again, they clearly state that ‘robust research with long-term follow-up is needed.’

“What the public may not be aware of, is that it is relatively common for treatments to be offered in health and mental health, where the research evidence is still emerging and/or limited. The choice for clinicians is frequently whether to offer nothing – which is unlikely to be helpful – or offer something that we agree can be helpful for some people. In doing so, we recommend that the person undergoing these treatments gets the best possible information on what we know about their risks and benefits. For this reason, we very much welcome research studies, such as those released today, which help us fully understand what they may be.”

Conflicts of interest statement: I’m not aware of any potential conflicts of interest. My role with the NZCCP involves speaking on behalf of the organisation- specifically the Executive leadership team. We have approximately 1800 members, who hold a wide range of views, and so my comments may or may not reflect those of individual members. I also hold a Senior Lecturer position at Otago University, specialising in Neuropsychology.

Our colleagues at the UK Science Media Centre also gathered comments.

Professor Ashley Grossman FMedSci, Emeritus Professor of Endocrinology, University of Oxford, comments:

“For many years we have been using puberty blockers in young children who are going into early puberty to delay puberty to a normal time – this has been very successful with much detailed evidence.

“This is a different situation – this set of reviews is looking at using these drugs to delay normal puberty.  This very detailed set of analyses now suggests that there are not enough good data showing the long-term effects in children with gender dysphoria.  Indeed there are some recent early data (although not yet peer-reviewed or published) suggesting some of their effects on testes and sperm may not be reversible.

“One must realise that coming to terms that one may be trans-gender can be extremely distressing, and we certainly need more facilities to assist such individuals, and as adults treat them as rapidly as possible within specialist centres.  However, for children with gender dysphoria, these studies have shown that there is no good evidence for the routine use of puberty blockers, although that is not to discount that in occasional children and young adults they could be helpful.  What it does emphasise is that children in this category, who seem to be of greatly increased numbers, need very careful counselling, assistance and help through this difficult time.  It may be that a small number of these children should in the long term transition to a different sex, but routine puberty blocking treatment for this use has not yet been adequately studied, and many of these children may have other problems for which they need help.  More carefully run clinical trials are needed so that we can understand how and when such agents are justified and of benefit.”

Conflicts of interest: None.

Dr Gavin Stewart, Senior Lecturer in Evidence Synthesis, Newcastle University, comments:

“The reviews meet current methodological expectations and can be considered reliable.  This research synthesis identifies major deficiencies in the evidence base concerning puberty blockers and hormone treatment for gender transition.  It highlights uncertainties that are not reflected in guidelines that are too dogmatic and prescriptive given their reliance on expert judgement.  Little can be said with any certainty regarding puberty blockers and hormone treatment for gender transition and this should be more widely acknowledged by health professionals and advocates alike.”

Conflicts of interest: None.

*Note: Updated 11/4/24 with an amended conflict of interest statement.