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

BACKGROUND: In adolescents with severe and persistent gender dysphoria (GD), gonadotropin releasing hormone analogues (GnRHa) are used from early/middle puberty with the aim of delaying irreversible and unwanted pubertal body changes. Evidence of outcomes of pubertal suppression in GD is limited. METHODS: We undertook an uncontrolled prospective observational study of GnRHa as monotherapy in 44 12–15 year olds with persistent and severe GD. Prespecified analyses were limited to key outcomes: bone mineral content (BMC) and bone mineral density (BMD); Child Behaviour CheckList (CBCL) total t-score; Youth Self-Report (YSR) total t-score; CBCL and YSR self-harm indices; at 12, 24 and 36 months. Semistructured interviews were conducted on GnRHa. RESULTS: 44 patients had data at 12 months follow-up, 24 at 24 months and 14 at 36 months. All had normal karyotype and endocrinology consistent with birth-registered sex. All achieved suppression of gonadotropins by 6 months. At the end of the study one ceased GnRHa and 43 (98%) elected to start cross-sex hormones. There was no change from baseline in spine BMD at 12 months nor in hip BMD at 24 and 36 months, but at 24 months lumbar spine BMC and BMD were higher than at baseline (BMC +6.0 (95% CI: 4.0, 7.9); BMD +0.05 (0.03, 0.07)). There were no changes from baseline to 12 or 24 months in CBCL or YSR total t-scores or for CBCL or YSR self-harm indices, nor for CBCL total t-score or self-harm index at 36 months. Most participants reported positive or a mixture of positive and negative life changes on GnRHa. Anticipated adverse events were common. CONCLUSIONS: Overall patient experience of changes on GnRHa treatment was positive. We identified no changes in psychological function. Changes in BMD were consistent with suppression of growth. Larger and longer-term prospective studies using a range of designs are needed to more fully quantify the benefits and harms of pubertal suppression in GD.