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by Michael Biggs

Transgender Trend first examined the effects of Gonadotropin-Releasing Hormone agonist (GnRHa) on bone density in 2019. This was prompted by a study co-authored by Professor Gary Butler, the lead clinical endocrinologist for the Gender Identity Development Service (GIDS) at the Tavistock and Portman NHS Foundation Trust (Joseph, Ting, and Butler 2018; Joseph, Ting, and Butler 2019). The authors emphasized that adolescents administered with GnRHa had not experienced any decline in absolute bone density. As endocrinologists Dr William J. Malone and Dr Michael Laidlaw pointed out on Twitter, however, adolescence is a period of increasing bone density—this is the developmental stage when an individual lays down the bone mass that will last them the rest of their life. What matters, then, is the individual’s bone density relative to the norm for their age and sex, which is measured by the Z-score (standardized deviation from the population mean). The Z-scores of the patients at the GIDS had fallen significantly. Spurred by Laidlaw’s and Malone’s comments, I produced a graph to illustrate how these Z-scores had declined (the graph was crude because it had to be derived from the mean and standard deviation of Z-scores alone, because nothing more was reported by Butler’s study). My conclusion: ‘It is obvious that a substantial minority of the girls on GnRHa suffered from abnormally low bone density.’

This claim can be vindicated now that the Tavistock finally released a subset of data from their experiment with GnRHa on children aged 12 to 15. The data were released following Transgender Trend’s lengthy campaign to disclose the outcomes of the experiment, which included a formal complaint to the Health Research Authority. My reanalysis of these data is now published by the Journal of Paediatric Endocrinology and Metabolism. I find that after two years on GnRHa, the Z-scores for up to a third of the children had declined to below -2. Only about 2% of the population fall below this threshold, and this is the threshold of clinical concern. Indeed, the Tavistock’s 2011 experimental protocol initially excluded any child with a Z-score below -2. This restriction was subsequently relaxed, with the stipulation that the patient must understand the ‘risks of later osteoporosis’ (Amendment 1.2, 3 July 2012). The Patient Information Sheet, however, never mentioned osteoporosis; it stated merely ‘We do not know how blocker treatment in early puberty will affect bone strength …’ The experimental protocol provides evidence that Butler—one of the investigators in the project, led by Professor Russell Viner and Dr Polly Carmichael—understood that such low bone density indicates a risk of osteoporosis.

The graphs show my results in detail. The blue line shows the normal distribution of bone density in the population. For hip bone mineral density,the Z-scores of one third of the patients had fallen below -2. For spine bone mineral density, over a quarter of Z-scores had declined below this threshold. Some had even fallen below ‑3; such low bone density is extremely rare, found in only 0.13% of the population. Adjusting for height—bone mineral apparent density—does not attenuate the lowest values.

Does such abnormally low bone density increase the risk of bone fractures? One of the Tavistock’s patients who started GnRHa at age 12 then experienced four broken bones by the age of 16. We have no idea whether this was unusual because Butler and the other researchers collected no data on fractures. Dutch studies show that the accrual of bone density recommences when cross-sex hormones are taken from age 16, and so Z-scores increase (Klink et al 2015; Stoffers et al. 2019). But in many cases the recovery is partial, and the Z-scores do not return to the level registered at the onset of GnRHa. The Tavistock has given GnRHa to a child as young as 10 years old, and so the failure to accrue bone mass could last up to five years. The Tavistock never follow up GIDS patients once they turn 18—not even those who graduate to the adult Gender Identity Clinic in the Tavistock Trust itself—and so there is no way of knowing whether patients who experience abnormally low Z-scores for years in adolescence have experienced osteoporosis as adults.

The fact that adolescents undergoing puberty suppression failed to accrue bone mass—to the point where a significant minority ended up with abnormally low bone density—inspired Butler and his coauthors to make two recommendations (Joseph, Ting, and Butler 2019). One is to reduce the monitoring of bone density, which has ‘significant financial implications for healthcare providers’. The other is to change the computation of Z-scores; ‘reference ranges may need to be re-defined for this select patient cohort’. When a measure provides inconvenient results, stop measuring or choose another scale: that is how transgender medicine is practiced at the Tavistock.

The Tavistock’s Dutch counterparts at least provide practical advice: ‘Adolescents should be counseled on the importance of weight-bearing exercise, an adequate dietary calcium intake, sufficient sunlight exposure to ensure adequate vitamin D levels, or vitamin D supplementation’ (Schagen et al. 2020). But the Dutch researchers also apparently omitted to collect data on fractures. Their latest article (which acknowledges a research grant from Ferring Pharmaceuticals, the manufacturer of the GnRHa drug used in the Netherlands and Britain) suggests that future studies should ‘investigate clinically important outcomes such as fracture risk’ (Schagen et al. 2020).

Fifteen years ago the exponents of the Dutch protocol for transgendering children admitted that their patients could ‘end with a decreased bone density, which is associated with a high risk of osteoporosis’ (Delemarre-van de Waal & Cohen-Kettenis 2006). It is remarkable that the proponents of puberty suppression are only now contemplating collecting evidence on this key clinical outcome at some future date.