Tavistock’s Experimentation with Puberty Blockers: Scrutinizing the Evidence

by Michael Biggs, Dept of Sociology, University of Oxford

(2 March 2019)

In 2010, Tavistock and Portman NHS Trust’s Gender Identity Development Service (GIDS) launched a trial of puberty blockers for children in their early teens with gender dysphoria. This was—and remains—an experimental treatment. These drugs, Gonadotropin-Releasing Hormone agonists (GnRHa), have not been certified as a safe or effective treatment for gender dysphoria by their manufacturers, nor by the National Institute for Clinical Excellence.

The Director of GIDS, Polly Carmichael, was keenly aware of the controversy over these drugs. ‘The question is, if you halt your own sex hormones so that your brain is not experiencing puberty, are you in some way altering the course of nature?’ (Guardian, 14 August 2008). ‘[T]he debate revolves around the reversibility of this intervention—physical and also psychological, in terms of the possible influence of sex hormones on brain and identity development’ (Carmichael and Davidson 2009). Before 2010, GIDS administered blockers to children only when they reached 16; this is the age at which young people have the presumptive capacity to consent to medical treatment.

This cautious approach was vociferously opposed by two organizations devoted to transgendering of children, Mermaids and the Gender Identity Research and Education Society. As Carmichael later recounted: ‘There was a lot of pressure coming from certain group [sic] to introduce it—families were travelling abroad because they knew it was available in Holland and America. As a service, we didn’t have the evidence one way or the other, so the best way to do it was as part of a research study’ (Vice, 16 November 2016).

Tavistock Trust announced the study on its website in April 2011. It stated that GnRHa treatment ‘is deemed reversible’. This assertion contradicted the study’s own research protocol (which I obtained under Freedom of Information from the NHS Health Research Authority). ‘It is not clear [my emphasis] what the long term effects of early suppression may be on bone development, height, sex organ development, and body shape and their reversibility if treatment is stopped during pubertal development’ (Early Pubertal Suppression in a Carefully Selected Group of Adolescents with Gender Identity Disorder, 4 November 2010, Research Ethics Committee number 10/H0713/79). A paediatrician on the study team, Russell Viner, frankly acknowledged the risks. ‘If you suppress puberty for three years the bones do not get any stronger at a time when they should be, and we really don’t know what suppressing puberty does to your brain development. We are dealing with unknowns’ (Daily Mail, 25 February 2012).

The study received considerable publicity, being reported in the Mirror, the Daily Telegraph, and the Times. As Carmichael observed, ‘as professionals we need to be looking at the long term and making sure this treatment is safe’ (Daily Telegraph, 15 April 2011). The bare outlines of the study can be gleaned from a conference presentation and a half-page published abstract (Gunn et al. 2015a; Gunn et al. 2015b). From May 2010 to July 2014, 61 children were recruited; puberty blockers were administered to 50 of them, aged between 10 and 16.

Even before the final patient was enrolled, Carmichael announced success to the tabloid press. ‘Now we’ve done the study and the results thus far have been positive we’ve decided to continue with it’ (Daily Mail, 17 May 2014). In fact the decision had already been made, at least six months earlier (Daily Mail, 17 November 2013). Tavistock Trust then embraced the drug regime with enthusiasm. Three years later, GIDS (and its satellite operation in Leeds) had prescribed puberty blockers for a total of 800 adolescents under 18, including 230 children under 14 (Daily Mail, 30 July 2017). By 2018, new prescriptions were running at 300 per year (BBC News, 2 July 2018). Freedom of Information requests have failed to elicit more recent figures because GIDS does not collate basic data on this experimental treatment—and neither does the University College London Hospitals NHS Foundation Trust, which provides its endocrinology services.

Over a thousand adolescents have been given puberty blockers on the basis that the 2010–14 study yielded ‘positive’ results. Tavistock is surprisingly reticent to share these results with the scientific community. GIDS has a webpage on the evidence base for puberty blockers. It notes that ‘research evidence for the effectiveness of any particular treatment offered is still limited.’ There is no mention of its own study; it cites only research from the Netherlands. The former director of GIDS stated last year that the ‘project is ongoing and the results are yet to be published’ (De Ceglie 2018).

Diligent searching does, however, uncover some unpublished results. Most revealing is an appendix within a report to Tavistock’s Board of Directors (Carmichael 2015). It tracks the first 44 children on GnRHa, measuring changes after one year of the drug regime. The text is sometimes internally inconsistent and occasionally contradicts the tabulated figures, suggesting that it was prepared in haste. But we can summarize those changes that were reported as statistically significant (p-value < .05). Only one change was positive: ‘according to their parents, the young people experience less internalizing behavioural problems’ (as measured by the Child Behavior Checklist). There were three negative changes. ‘Natal girls showed a significant increase in behavioural and emotional problems’, according to their parents (also from the Child Behavior Checklist, contradicting the only positive result). One dimension of the Health Related Quality of Life scale, completed by parents, ‘showed a significant decrease in Physical well-being of their child’. What is most disturbing is that after a year on blockers, ‘a significant increase was found in the first item “I deliberately try to hurt or kill self”’ (in the Youth Self Report questionnaire). Astonishingly, the increased risk of self-harm attracted no comment in Carmichael’s report. Given that puberty blockers are prescribed to treat gender dysphoria, it is paradoxical that ‘the suppression of puberty does not impact positively on the experience of gender dysphoria’ (measured by the Body Image Scale). When differentiated by sex, the impact was positive for boys on one aspect of body image, but negative for girls on two aspects.

These preliminary results (44 children after one year on GnRHa) were also presented at a symposium at the World Professional Association for Transgender Health (Carmichael et al. 2016). Only the abstract is available. ‘For the children who commenced the blocker, feeling happier and more confident with their gender identity was a dominant theme that emerged during the semi-structured interviews at 6 months. However, the quantitative outcomes for these children at 1 years time suggest that they also continue to report an increase in internalising problems and body dissatisfaction [my emphasis], especially natal girls.’ Why were these negative results never published?

The study apparently contributed data on outcomes to one publication, coauthored by Carmichael (Costa et al. 2015). The abstract proclaims that ‘adolescents receiving also puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa … compared with when they had received only psychological support’. The article is treated in the literature (e.g. Heneghan and Jefferson 2019) as providing evidence in favour of puberty blockers. But the abstract is misleading: the analysis actually failed to detect any difference between children who were given blockers and those who were not. To understand this, we need to scrutinize the article in detail. (Statistically minded readers will recognize the fallacy described by Gelman and Stern 2006.)

The analysis starts with 201 adolescents diagnosed with gender dysphoria. The children were divided into two groups: those deemed eligible for puberty blockers immediately, and those who needed more time due to ‘comorbid psychiatric problems and/or psychological difficulties’. This second group did not receive any physical intervention during the time of this analysis, and so serves as a control group. Both groups received psychological support. The article chooses one outcome, psychosocial functioning as measured by the Children’s Global Assessment Scale (CGAS). This scale was administered at the outset, and then after six, twelve, and eighteen months. It is intriguing that the article omits the outcomes that were negative in the preliminary results: the Child Behavior Checklist, the Youth Self Report Questionnaire, the Health Related Quality of Life scale, and the Body Image Scale.

The authors graph the CGAS results, but without confidence intervals—which indicate the extent of random statistical variation or noise. The smaller the sample, the greater this noise. These samples shrank over time: after eighteen months, the group getting puberty blockers numbered only 35, and the control group 36. The article does not explain why two thirds of the subjects disappeared. Presumably they did not stop the medication, because all 50 children given blockers in the 2010–14 study continued the drug regime for two years (Gunn et al. 2015b).

My graph plots the results with standard 95% confidence intervals. The group given puberty blockers from six months onwards showed improvement at eighteenth months: the average CGAS score had increased from 61 to 67 (coloured red on the graph). This improvement is statistically significant, and it is the one that the authors chose to highlight. However, these children also received psychological support, and so attributing this improvement to medical intervention is unjustified. The crucial comparison is between the group receiving blockers and the control group. The latter’s average CGAS score (coloured blue) after eighteen months was lower, 63 compared to 67. But this difference is not statistically significant; the 95% confidence intervals substantially overlap. (For statistically minded readers, a two-tailed t-test for the difference between group means yields a p-value of .14, far beyond the conventional .05 threshold.) In other words, the samples were so small, and there was such wide variation in scores within each group, that we can draw no conclusions. There is no evidence that puberty blockers improve psychosocial functioning. Presumably this is why GIDS omits the article from its own evidence base.

The abstract describing the baseline characteristics of the children in the 2010–14 study concluded: ‘Assessment of growth, bone health and psychological outcomes will [my emphasis] be important to assess the medium and long-term safety and effectiveness of early intervention’ (Gunn et al. 2015b). However, GIDS apparently failed to collect any data on its experimental subjects after they turned 18. In a startling admission, Carmichael and coauthors blame ‘the frequent change in nominal and legal identity, including NHS number in those referred on to adult services’—‘to date they have not been able to be followed up’ (Butler et al. 2018). (Transgender activists successfully lobbied the NHS to provide new numbers to patients as well as to change the ‘gender’ on their medical records.)

To summarize, GIDS launched a study to administer experimental drugs to children suffering from gender dysphoria. Between 2010 and 2014, puberty blockers were given to 50 children. This study yielded only one published scientific article on outcomes. It showed no evidence for the effectiveness of GnRHa: there was no statistically significant difference in psychosocial functioning between the group given blockers and the group given only psychological support. In addition, there is unpublished evidence that after a year on GnRHa children reported greater self-harm, and that girls experienced more behavioural and emotional problems and expressed greater dissatisfaction with their body—so puberty blockers exacerbated gender dysphoria. Yet the study has been used to justify rolling out this drug regime to several hundred children aged under 16. Almost five years after the last patient was enrolled in the experiment, there is no evidence to substantiate Carmichael’s claim ‘that the results thus far have been positive’.

The Director of GIDS needs to answer these questions about the 2010–14 experimentation with puberty blockers:

On what evidence did you claim in 2014 that ‘the results thus far have been positive’?

When preliminary results in 2015 showed that children after a year on blockers showed a statistically significant increase in reported self-harm, was this ever investigated?

Why did you never publish the negative results reported to Tavistock’s Board of Directors in 2015 and to WPATH in 2016?

Why did your only published article (Costa et al. 2015) using data from the study omit all the outcomes that were negative in the preliminary results (Child Behavior Checklist, Youth Self Report questionnaire, Health Related Quality of Life scale, and Body Image Scale)?

In your article, why did the abstract and conclusion not report the finding that there was no statistically significant difference between the group given GnRHa and the control group?

In your article, what accounts for the reduction in the number of subjects from 201 to 71 over eighteen months?

What steps have you taken to monitor the ‘long-term safety and effectiveness of early intervention’, as these experimental subjects become adults?

Note

How many subjects from the 2010–14 study are included in Costa et al. (2015) is unclear. The 2010–14 study gave GnRHa to 50 adolescents, starting at ages from 10 to 16 (Gunn et al. 2015a, 2015b). One would expect all of them to be included in the ‘immediately eligible’ group in Costa et al. (2015), along with some older adolescents to boost the sample size. The article counts 101 children in this group at 6 months when GnRHa commenced (Table 2), starting at ages from 13 to 17 (Table 1). The age range indicates the exclusion of some children from the 2010–14 study: those who commenced GnRHa from ages 10 to 12. Why? Another puzzle is worth noting. When I requested the Research Ethics Committee number from Tavistock and Portland NHS Trust under Freedom of Information, it provided the number 10/H0718/62. According to the NHS Health Research Authority, however, this number refers to a study that was given an ‘unfavourable opinion’ and therefore could not proceed.

References to the 2010–14 GIDS Study

Carmichael, Polly, 2015, ‘Preliminary Results from the Early Intervention Research’, Appendix 7 in ‘Service Line Report: Gender Identity Development Service (GIDS)’, Tavistock and Portman NHS Trust, Board of Directors Part One: Agenda and Papers … 23rd June 2015, pp. 50–55.

Carmichael, Polly, Sally Phillott, Michael Dunsford, Amelia Taylor, and Nastasja de Graaf, 2016, ‘Gender Dysphoria in Younger Children: Support and Care in an Evolving Context’, World Professional Association for Transgender Health 24th Scientific Symposium.

Costa, Rosalia, Michael Dunsford, Elin Skagerberg, Victoria Holt, Polly Carmichael, and Marco Colizzi, 2015, ‘Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria’, Journal of Sexual Medicine, vol. 12, pp. 2206–14.

Gunn, H.M., C. Goedhart, G. Butler, S.N. Khadr, P.A. Carmichael, R.M. Viner, 2015a, ‘Gender Dysphoria: Baseline Characteristics of a UK Cohort Beginning Early Intervention’, presented to the Youth Health Conference, Australia.

Gunn, H.M., C. Goedhart, G. Butler, S.N. Khadr, P.A. Carmichael, R.M. Viner, 2015b, ‘Early Medical Treatment of Gender Dysphoria: Baseline Characteristics of a UK Cohort Beginning Early Intervention’, Archives of Disease in Childhood, vol. 100, supp. 3, p. A198.

Acknowledgements

Valuable information was provided by Stephanie Davies-Arai, Susan Matthews, Heather Brunskell-Evans, and Twitter’s @neverfallingfo1.

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