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This study has now been published in the peer-reviewed journal PLOS ONE:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243894
Starting in 2011, the Gender Identity Development Service at the Tavistock undertook the Early Intervention Study to provide a research framework to the lowering of the age at which young people could access puberty blockers from 16 to 12. Today, a peer-reviewed paper published in PLOS one, describes the medical, psychological and social outcomes for young people with persistent and severe gender dysphoria treated with puberty blockers.
The paper, by a team of Gender Identity Development Service (GIDS) clinicians and independent researchers, including eminent professors of medical statistics and paediatric endocrinology, reports on the cohort of 44 young people enrolled in the study between 2011 and 2014. The study also evaluated the efficacy of treatment and considered the persistence of gender dysphoria and decisions about future treatment.
The participants attended GIDS at the Tavistock and Portman NHS Foundation Trust where they were assessed and received psychological support. They were referred to University College London NHS Foundation Trust for physical evaluation and treatment. All patients achieved and maintained suppression of pubertal hormones and none experienced pubertal progression. At the end of the study, 43 (98%) chose to start cross-sex hormones whilst one young person chose to stop GnRHa and continue with puberty consistent with their birth-registered sex.
The paper, ‘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’, shows that overall patient experience of changes on gonadotropin releasing hormone analogues (GnRHa) treatment (commonly called ‘puberty blockers’) was positive and there were no unexpected adverse events. Those expected adverse effects reported (headaches, flushes, fatigue, etc) were mainly mild.
The study identified little change in psychological functioning, but the experience of treatment as reported in interviews was positive for most. The majority reported feeling happier and having better relationships with family and peers once treatment had begun. However, some reported negative changes, which were largely related to the anticipated side effects.
For the study, a highly selected group of young people who along with their families were actively seeking this treatment and fulfilled the eligibility criteria were invited to take part after lengthy assessments (two years on average). These young people had been experiencing gender dysphoria which had been consistent and persistent over at least 5 years and had significantly increased with the onset of puberty, with a high likelihood of severe psychological distress on facing full pubertal development. A key purpose of GnRHa treatment is to pause puberty, to avoid a deterioration in wellbeing and allow for further exploration of a young person’s feelings about their gender identity and their wishes for the future, without the pressure or distress which may come from further unwanted bodily changes. The lack of change observed in psychological function can signify one of two things. Either that GnRHa treatment brought no measurable benefit nor harm to psychological function. Or that the lack of change in an outcome that normally worsens in early adolescence may reflect a beneficial change in trajectory for that outcome, i.e. that GnRHa treatment prevented a typical deterioration of psychological function over this period.
The young people involved in this study experienced severe gender dysphoria which had persisted into adolescents and the early stages of puberty. The fact that 43 out of 44 of them went on to access gender-affirming hormones is consistent with other studies internationally where the discontinuation rate varies, but is typically in the 2-5% range. However, one young person did stop treatment without progressing to cross-sex hormones. This provides some evidence that development of gender identity continues on GnRHa treatment and confirms the importance of continuing supportive psychological therapy to allow further exploration of gender identity and a range of future pathways whilst on this treatment. It is also worth noting that three participants had periods off treatment before they were 16 for a range of reasons demonstrating further that patients can and do decide to interrupt treatment.
As anticipated, pubertal suppression reduced growth affecting both height and bone mass density. In both cases (height and bone strength) there was some growth but less than would be expected during those years without hormonal suppression. There was no loss of bone density over the study period and the expectation is that the resumption of growth on both counts would be achieved when puberty resumed either naturally or via cross-sex hormones administered from 16. Further papers on bone strength have been published (inc. by some of the authors) supporting this hypothesis though research into long-term bone mass density recovery on this treatment pathway is underway.
Overall, the paper suggests that larger and longer-term prospective studies using a range of designs are needed to more fully quantify the benefits and limitations of pubertal suppression for those experiencing gender dysphoria. The study size and uncontrolled design were key limitations, meaning small changes in outcomes and causality could not be determined.This cohort will be followed up longer-term to examine physical and mental health outcomes into early adulthood.
Dr Polly Carmichael, Director of GIDS, says: “This paper adds to our understanding of the best way to support these young people. The results show patient experience on the blocker is positive overall and there were no unexpected adverse events, but that more research is needed around this complex issue.”
Professor Russell Viner, Professor of Adolescent Health at University College London (UCL), added: “At all stages of the process we have followed rigorous ethical guidelines. We have published findings in an open access international peer-reviewed journal with open peer review. We have also placed carefully anonymised data from the study in the public domain to allow other researchers to replicate our main findings.”
Professor Tim Cole, Professor of Medical Statistics at UCL, explained: “The formal analysis plan protected against drawing unwarranted conclusions given the small and uncontrolled study sample.”
Professor Gary Butler, Consultant in Paediatric and Adolescent Medicine and Endocrinology at University College Hospital London NHS Foundation Trust said: “We are glad to add to the evidence base for the puberty blocker, showing its safety and the value this treatment has for young people.”
Read the paper on the PLOS ONE website.
The study to evaluate of early pubertal suppression was begun in 2011/12 in response to broadening use of early pubertal suppression treatments across Europe and in the USA and Australia and emerging evidence of benefits and safety from Amsterdam University.
Previous to this study, physical treatment for Gender Dysphoria (previously known as Gender Identity Disorder or GID) for adults in the UK was provided according to the guidance of the Royal College of Psychiatrists (RCPsych). This was published in 1998 and then adopted in the Standards of Care of the Harry Benjamin Gender Dysphoria association, which is now the World Professional Association for Transgender Health (WPATH).
In the Royal College of Psychiatrists Guidelines physical interventions were classed in three groups:
At the time, treatment for young people was provided in accordance with the RCPsych guidelines and restricted to wholly reversible interventions. Routine practice in the London service prior to the early puberty suppression study was that pubertal suppression was available for suitable patients over the age of 16 years, using gonadotrophin-releasing hormone analogues (GnRHa). Patients were considered eligible if they were fully pubertal, had persistent Gender Dysphoria, had no other endocrine disorders and understood the risks and benefits of GnRHa (i.e. could provide informed consent). The use of pubertal suppression was to induce a sex-hormone-neutral environment to provide young people with space to decide whether to progress further with gender reassignment treatment as an adult.
The London service had many years of experience of using GnRHa in young people with Gender Dysphoria who were 16 years or over. Treatment, if instituted, was continued for 18-24 months before commencement of cross-sex hormones (testosterone or oestrogen), i.e. at age 17.5-18 years. Medically, pubertal suppression allowed the institution of cross-sex hormones at low doses which were gradually increased over 2 years. Given that young people moved to adult services at age 18 years, this largely meant that they accessed cross-sex hormones after they were established in adult services.
In the 8 years before the commencement of the study, the London service was involved in extensive exploration of the issues and possible risks and benefits of earlier pubertal suppression. This included a number of national and international meetings. The clinical and ethical issues related to the timing of pubertal suppression in adolescents with Gender Dysphoria in the UK compared with other countries were discussed at the Ethics and Law session of the Royal College of Paediatrics & Child Health (RCPCH) Annual Meeting in March 2005.[1] Issues were discussed again at the Royal Society of Medicine (RSM) on 10 October 2006. A meeting was held between the London service with clinical academics from Amsterdam University (Prof. H. Delamerre; Prof. P Cohen-Kettenis) and from Harvard University (Prof. Norm Spack) (meeting in Amsterdam, 1 June 2007). A further large international meeting was held at the RSM on 1 October 2008. The RSM meeting included a large number of paediatric endocrinologists (Prof. Ieuan Hughes, University of Cambridge; Dr. Liz Crowne, Chair of the British Society for Paediatric Endocrinology & Diabetes (BSPED)) and adult endocrinologists (Prof. John Wass, Oxford University; Prof. Mike Besser, Barts) from the UK as well as clinical academics from the Netherlands, Canada and elsewhere.[2] The meeting included presentations by sociologists, brain scientists (Prof. Sarah-Jane Blakemore, UCL) psychologists (Prof. Ken Zucker, Toronto; Prof. Melissa Hines, University of Cambridge) as well as a presentation on ethics by Dr Vic Larcher, Chair of the Great Ormond Street Hospital Clinical and Ethical Committees and of the Ethics Committee of the Royal College of Paediatrics and Child Health. A separate meeting was hosted by Imperial College on 28 September 2008 by Prof. Richard Green, as he and others claimed that “the UK’s conservative approach will dominate the conference on gender identity disorder in adolescents at the Royal Society of Medicine (RSM)”.[3]
Each of these meetings reviewed emerging data from the Dutch service and elsewhere (e.g. Gent, Boston, Oslo, Toronto, Melbourne) on the increasing use and outcomes of pubertal suppression under age 16 years.[4] In each meeting the Dutch, US and some UK clinicians were clear that they considered the UK service to be an outlier in not supporting pubertal suppression under 16 years as had become standard practice in overseas centres. A review by an ethicist Dr. Simona Giordano, University of Manchester, published in The Journal of Medical Ethics in July 2008, argued that the UK position of not offering early pubertal suppression was unethical.[5]
Much of the debate focused upon whether young adolescents could consent to treatments due to the potential for unknown risks or harms in the future. The Dutch clinicians argued that the consequences of non-treatment (i.e. psychological harms; potential for self-harm) were likely to be greater than those of treatment.[6] Dr. Giordano, an ethicist, argued strongly that it was in the best interests of the child to offer earlier pubertal suppression, that arguments about irreversibility were spurious[7] and that if it were impossible to consent to interventions whose outcome is uncertain, much medical research involving human beings would be unethical.[8]
There was considerable dissatisfaction by patients with the situation in the UK, with a number of parents electing to take their children overseas for treatment, particularly to the USA. This was documented at the time.[9] Service users linked with the Tavistock & Portman NHS Foundation Trust and charities supporting trans groups were strongly supportive of introducing early pubertal suppression.
[1] Viner R, Brain C, Carmichael P, DiCeglie D. Sex on the brain: Dilemmas in the endocrine management of children and adolescents with Gender Identity Disorder. G200: Ethics and law and palliative medicine joint session Archives of Disease in Childhood 2005;90:A77-A81. https://adc.bmj.com/content/90/suppl_2/A77
[2] The meeting was summaried by Assherman H. Gender identity disorder in adolescents. Sexologies Volume 18, Issue 2, April–June 2009, Pages 105-108. https://doi.org/10.1016/j.sexol.2009.02.001
[3] Richard Green. Young transsexuals should be allowed to put puberty on hold. The Guardian Thu 28 Aug 2008. https://www.theguardian.com/commentisfree/2008/aug/28/sexeducation.gayrights
[4] Cohen-Kettenis P, Delemerre-van de Waal H, Gooren L. J Sex Med 2008; 5: 1891-97. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1743-6109.2008.00870.x
[5] Giordano S. Lives in a chiaroscuro. Should we suspend the puberty of children with gender identity disorder?
Journal of Medical Ethics 2008;34:580-584.
[6] Cohen-Kettenis P, Delemerre-van de Waal H, Gooren L. J Sex Med 2008; 5: 1891-97. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1743-6109.2008.00870.x
[7] Giordano S. Lives in a chiaroscuro. Should we suspend the puberty of children with gender identity disorder?
[8] Giordano S. Gender atypical organisation in children and adolescents: Ethico-legal issues and a proposal for new guidelines. International Journal of Children’s Rights. 2007;15 (3):365-390 DOI: 10.1163/092755607X262793
[9] Giordano S. Lives in a chiaroscuro. Should we suspend the puberty of children with gender identity disorder?
There is a considerable and lengthy experience amongst paediatric endocrinologists of the use of GnRHa for suppression of puberty. Some GnRHa are licensed in the UK for use in children for precocious puberty i.e. conditions where children began puberty early. GnRHa were not licensed for use in Gender Dysphoria, and thus their use would be ‘off-license’. Note that at the time, it was estimated that over half of drugs prescribed by Paediatricians for children were ‘off-license’. This situation had developed because drug companies were reluctant to seek a license for use in children for many common drugs for a variety of reasons, and despite considerable action on this across children’s medicine in the last decade, this remains substantially the case. Thus, use of a drug for a child ‘off-license’ was a relatively routine event.
In the UK, it became clear during and after the 2008 RSM meeting that there was a considerable body of opinion amongst paediatric endocrinologists and some adult endocrinologists that: i) given the considerable experience of safe use of GnRH analogues for pubertal suppression in precocious puberty in young children; and ii) that the effects of GnRH analogues on pubertal hormones were rapidly reversible; that strong consideration should be given to introduction of pubertal suppression under 16 years.
It was noted in later applications to the ethics committee that we had consulted with eminent academics such as Professor Peter Fonagy (Psychology, UCL) and Professor Ieuan Hughes (Paediatrics & Paediatric Endocrinology, University of Cambridge). It was also noted that we had consulted with some young people and families attending the London service and had sought their views about the proposed research, which were highly supportive.
Prof. Ieuan Hughes, a paediatric endocrinologist and then Professor of Paediatrics at the University of Cambridge, was consulted extensively in the years running up to the study. He was strongly supportive of enabling the availability of early pubertal suppression in the UK, as evidenced by a lecture he gave at the British Endocrine Society on 17 March 2010 in Manchester. Hughes in this talk was interested in identifying when the physical changes of puberty became irreversible – making the argument that there was a window of opportunity for intervention between Tanner stage 2 (early puberty) and Tanner stage 4 (late puberty). In particular he noted that voice-breaking occurred suddenly between Stage 3 and 4, and that treatment should be instituted before this in male-to-female patients.
The Endocrine Society (USA) together with the European Society of Endocrinology, European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society (USA), published a new position statement in 2009 advocating that GnRHa be used to suppress puberty in adolescents at Tanner stage 2 or above until age 16 years old, after which cross-sex hormones could be given.[1]
In April 2010, Prof. Hughes provided considerable advice on a proposed UK early intervention study from an endocrine point of view, noting “I am pleased that the Tavistock Clinic intends to undertake this project as there is abundant evidence from longstanding correspondence of the widespread dissatisfaction with the disconnect between the London practice and other centres around the world.”[2]
The British Society for Paediatric Endocrinology and Diabetes (BSPED) was involved and supported the early intervention study, particularly given the support for the 2009 Endocrine Society guideline from the European Society of Paediatric Endocrinology (ESPE). Prof. Hughes noted that “BSPED had encouraged the development of research in conjunction with supporting the case for the Tavistock clinic to be NCG recognised.”[3]
The proposed study was further discussed as part of a seminar at the Royal College of Paediatrics and Child Health Annual Meeting in Warwick on 8 April 2011, Sex and Development in Children and Young people: from DSD to Gender Dysphoria.
In 2012, clinical academics from the Royal Children’s Hospital in Australia published outcome data on small numbers of young people who had begun early pubertal suppression (10-16 years) in Melbourne Australia, with no young people ceasing hormone treatment.[4] This provided evidence that early pubertal suppression was increasingly being used outside early adopter services in Amsterdam and Boston.
In essence, as noted in the ethics application, the ethical issue that had arisen is that young people and their families wished to exercise choice to begin a treatment which was then offered in major centres internationally and was endorsed by authoritative international guidelines but for which the evidence base was low. There were theoretical risks but no evidence of harms in published data. The London service proposed to offer early pubertal suppression in the UK according to the Endocrine Society guidelines but initially only within a research protocol. This therefore offered families a choice of treatments within a framework with a robust system of outcome monitoring and in the safest possible way.
[1] Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2009; 94(9): 3132-54
[2] Correspondence, I. Hughes to D. Di Ceglie, April 2010.
[3] Correspondence, I. Hughes to S. Khadr, 25 September 2012.
[4] Hewitt JK, Paul C, Kasiannan P, Grover SR, Newman LK, Warne GL. Hormone treatment of gender identity disorder in a cohort of children and adolescents Med J Aust 2012; 196 (9): 578-581. || doi: 10.5694/mja12.10222
We undertook an uncontrolled treatment cohort study of 12-15 year old young people with established and persistent Gender Dysphoria in England. This study design was appropriate to evaluate the central question of the study, i.e. whether a timing modification of standard treatment (GnRHa for pubertal suppression), was safe and effective.
A number of study designs were considered for evaluating the effects of early pubertal suppression. We consulted various clinical trial experts on this; e.g. Prof. Ian Wong, then professor of Paediatric Pharmacy at the Institute of Pharmacy. After much discussion within the team and with colleagues (e.g. at BSPED, Prof. Hughes, Prof. Wong) and some discussions with patient groups, a decision was made that we did not feel that a randomised controlled trial (RCT) was feasible in this situation. An RCT would have compared early pubertal suppression with standard treatment (i.e. pubertal suppression after 16 years). Whilst this would have theoretically provided the highest level of evidence, it would require young people and families to accept they had a 50:50 chance of being assigned to standard treatment. At the time, there was long-term criticism of the service for not offering early pubertal suppression and there was evidence of increasing numbers of families going overseas for private treatment. Further, recruitment would only be offered to highly motivated individuals who had demonstrated many years of persistence in their gender identity disorder, that is, in their belief and wish to change their body to match their internal perception. We believed that people in this state of mind and with this level of conviction about their identity were therefore unlikely to accept randomisation to something other than the treatment they desired. We concluded that few patients would accept randomisation to standard treatment, which would either majorly compromise recruitment or alternatively collapse the trial (by drop out from the control arm after randomisation). We noted that the same conclusion had been reached by the Amsterdam clinical academics.[1]
The likely small numbers of patients eligible or desiring early pubertal suppression also made us believe that a randomised trial would not be feasible, particularly if recruitment would be very problematic. We estimated that around 15 patients per year would fulfil criteria for treatment – an estimate later proved accurate as we recruited 44 patients to the study over 3 years. An RCT with only 20-25 subjects per arm would be very underpowered to identify any but very large effect sizes and would be very vulnerable to recruitment difficulties. At the time of these discussions, the Dutch service were publishing outcome data on 70 young people given early pubertal suppression[2] and the null or small effects shown did not support undertaking an RCT with the projected sample size and indeed published outcome data out to 22 years after early pubertal suppression.[3].
We concluded that it would be unethical to embark on an RCT which was unfeasible. We further concluded that a prospective uncontrolled treatment cohort was the only feasible study design.
We inquired with the MHRA regulatory body on 14 April 2010 which confirmed on 15 April that an evaluation of timing change (i.e. earlier) use of a drug (GnRH analogue, Triptorelin) routinely used within our clinical practice at 16 years plus, did not constitute a clinical trial of an investigational medicinal product and thus did not need MHRA authorisation.
[1] De Vries, A. L., Steensma, T. D., Doreleijers, T. A. and Cohen-Kettenis, P. T. Puberty suppression in adolescents with gender identity disorder: A prospective follow-up study. The Journal of Sexual Medicine 2011; 8: 2276-83
[2] De Vries, A. L., Steensma, T. D., Doreleijers, T. A. and Cohen-Kettenis, P. T. Puberty suppression in adolescents with gender identity disorder: A prospective follow-up study. The Journal of Sexual Medicine 2011; 8: 2276-83
[3] Whilst only a case study, this report shows the length of time the Dutch had been evaluating early pubertal suppression. More detailed data on the Dutch series were published elsewhere. Cohen-Kettenis, P. T., Schagen, S. E., Steensma, T. D., de Vries, A. L., & Delemarre-van de Waal, H. A. (2011). Puberty suppression in a gender-dysphoric adolescent: a 22-year follow-up. Archives of sexual behavior, 40(4), 843–847. doi:10.1007/s10508-011-9758-9
Ethics approval for the study was granted by the National Research Ethics Service Central London Research Ethics Committee 2, on 28 February 2011 (REC reference no: 10/H0713/79). The lead sponsor was the UCL Institute of Child Health, with UCL Hospitals NHS Trust as the lead R&D office.
The ethics application outlined potential risks and benefits of early pubertal suppression and consideration of different research designs.
A previous application to the Central London Research Ethics Committee (REC) 1 had not been approved. The reason given for this was that REC 1 advised that they believed that a randomised controlled trial should be the chosen study design: they noted that “Whilst there was a range of opinions expressed by individual committee members including some who were happy to approve the study, there was a significant number who felt that to proceed on the basis proposed without due consideration of alternative study design was unethical.”
We subsequently duly considered the alternative study designs suggested. We concluded again that a randomised controlled trial was not practical as:
i) numbers were likely to be too small; we anticipated recruiting only 10-15 young people per year at that time, very likely to provide an underpowered study even if fully recruited;
and
ii) we were very unlikely to be able to retain young people in the control group, given that increasing numbers were opting for private treatment overseas. A delayed start control situation was not a potential alternative in this situation, as the treatment protocol relied on commencing treatment in the narrow window between puberty stage 2-3 and full puberty, and a delayed start control would have meant that those in the control situation were allowed to fully enter puberty. Again this would have very likely been unacceptable to young people and families, whose aim was to avoid full puberty. Novel designs which included giving patients choice of treatment regimen were also infeasible as we believed it extremely unlikely that any families would choose the control for reasons given above.
We believed that a failed trial would be an inevitable result of opting for a randomised controlled design of any type, and that this was not in the best interests of patients as it would not provide data to advance the field. We noted that the same conclusion was reached by the Dutch group who had published longitudinal follow-up. We also noted that the Amsterdam University VU Medical Centre ethics committee had approved the Dutch approach on this.[1]
The options after an unfavourable opinion are to submit again to the original REC or to seek an opinion from another REC, providing all information from the first application. The investigators had attended the REC1 meeting and discussed the issues relating to study design. After further consideration of the alternative study designs suggested, we decided not to appeal to REC1 but concluded that a different REC with greater experience of dealing with rare conditions in children and issues relating to parent and child choice would better understand the issues. We elected to submit a revised application to REC 2. We wrote to the REC2 Chair outlining the responses to the decision by REC1 and why we disagreed with their conclusions. REC2 were supplied with the original application to REC1, their decision letter and the response. Protocol version 1.0 was the accepted version.
After the favourable opinion from REC2 was received, recruitment to the study began in April 2011.
An amendment was submitted and approved in October 2011 to modify the eligibility criteria for body mass index (BMI) and bone mineral density (BMD). The original criteria excluded those with BMI or BMD below 15th centile, which effectively excludes 15% of the population and thus excludes a number with normal BMI and BMD. The ethics committee approved modification of eligibility to <2% (i.e. <z-score of -2) for BMI and BMD.
An amendment (Protocol version 1.2; 4-7-2012) was submitted and approved in July 2012 to modify the then current exclusion criteria to allow young people with BMD >2SD for age below mean to participate if they were able to give informed consent to the risks entailed upon entering treatment with a relatively low bone mineral content for age. It was noted that the investigators believed that the then current method of assessing BMD (two dimensional assessments) were likely to underestimate BMD in slim slender-boned young people.
Informed consent for participation was obtained from young people themselves and from a parent with parental responsibility. All young people and families were given more than 1 month between discussion of the study and risks and benefits and signing consent to participate – in practice this was always 2 months or more. The Patient Information Sheet was approved by the Research Ethics Committee as part of the application.
No funding was received for this study from outside the NHS. There was also no specific NHS funding received – however the study was conducted within the NHS, using NHS resources (clinician time, data storage) where available.
In September 2012, we updated BSPED through Prof. I. Hughes on progress of the study, noting that 15 young people had been recruited, and provided a report to BSPED for their November 2012 meeting.
The following outputs from the study have been prepared, presented and/or published:
It stated in the ethics application that some data would be analysed at the end of 3 years and an interim report produced. A number of interim outputs and reports from the study were presented and published as follows:
1. Di Ceglie et al. Psychosocial aspects of adolescents with Gender Identity Disorder carefully assessed for early pubertal suppression. Royal College of Psychiatrists Faculty of Child and Adolescent Annual Meeting, 18-21st September 2012, Manchester Conference Centre. This presented data on the first 18 young people recruited to the study.
2. Gunn H, Goedhard C, Butler G, Khadr S, Carmichael P, Viner R. Early medical treatment of Gender Dysphoria: baseline characteristics of a UK cohort beginning early intervention. Archives of Disease in Childhood 2015;100:A198. https://adc.bmj.com/content/100/Suppl_3/A198.1. This examined the early outcomes from 61 young people referred for consideration of pubertal suppression. This included the 44 from the early intervention study plus other young people who were not eligible for this study due to being further developed in puberty and were treated at 15 years. Additional young people were included to improve the sample size for analyses. The presentation noted that all who began GnRHa achieved full gonadatropin suppression. No young people withdrew from GnRHa treatment in the first 2 years.
3. Carmichael P, Viner R. Seminar: Physical intervention in early puberty in the UK: Report from a research study. Transgender health from global perspectives. WPATH Symposium, Bangkok 14-18 Feb 2014. This reported qualitative data on early outcomes of 44 young people who received early pubertal suppression. It noted that 100% of young people stated they wished to continue on GnRHa, that 23 (52%) reported an improvement in mood since starting the blocker but that 27% reported a decrease in mood. Noted that there was no overall improvement in mood or psychological wellbeing using standardized psychological measures.
4. Carmichael P, Viner R. Early pubertal suppression in GID. Turin University, 27 January 2015. This was a presentation of outcomes thus far from the study, at a scientific meeting in Turin, Italy.
5. Carmichael P. Time to reflect: Gender Dysphoria in children and adolescents, defining best practice in a fast-changing context. Plenary Lecture on 18 June 2016: WPATH 24th Scientific Symposium, Amsterdam, 17-21 June 2016.
Joseph T, Ting J, Butler G.
The effect of GnRHa treatment on bone density in young adolescents with Gender Dysphoria: findings from a large national cohort Endocrine Abstracts (2018) 58 OC8.2 | DOI: 10.1530/endoabs.58.OC8.2
Joseph T, Ting J, Butler G. The effect of GnRH analogue treatment on Bone Mineral Density in very young adolescents with Gender Dysphoria from a large national cohort.
J Ped Endo Metab (In press).
These showed that there is no actual change in bone mineral density in young transgender adolescents on long-term GnRHa therapy (when measured as BMAD or tBMD). This confirms that long-term GnRHa treatment has minimal impacts upon bone health, one of the major concerns about treatment.
Matteo Catanzano, Gary Butler. Effect of Pubertal Blockade and Cross-sex Hormone Treatment on the Growth Spurt in Young Transgender Adolescents: A First Report
Horm Res Paediatr 2018;90(suppl 1):p505 P1-P211. DOI: 10.1159/000492307
This showed that only 14 of the cohort of 44 in the study had reached final adult height at time of data collection. Data were therefore insufficient to comment on impact of GnRHa on final height.