Early Intervention Study shows puberty blockers are a well-received intervention in carefully selected patients

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.