Summary

This was the UK's own test of puberty blockers, run by the Tavistock's gender clinic for children from 2011. Forty-four carefully chosen 12–15-year-olds were given a blocker drug and followed until they were over 16. The blockers paused puberty as intended. But there was no measurable change in emotional distress, self-harm, quality of life or gender distress, and bone density fell behind other teens their age. Most young people spoke positively about the treatment in interviews, and 43 of 44 went on to cross-sex hormones. The authors call for larger studies. There was no comparison group, numbers fell sharply after the first year, and a later re-analysis found up to a third got worse. So the study offers no evidence that blockers help mental health.

Key findings

• 44名12至15岁（25名出生时为男性，19名出生时为女性）有严重而持久的性别痛苦的年轻人，在诊所通常经过两年评估后，于2011至2015年间开始使用青春期阻断剂。
• 在1年、2年或3年后，无论是家长还是年轻人都没有报告情绪或行为问题或自伤方面的任何变化。
• 生活质量、对自己身体的感受、性别痛苦以及应对情况（由临床医生判断）也几乎没有变化；作者指出，阻断剂不会使身体向所期望的性别转变。
• 下背部的骨密度增长比其他青少年更慢，因此相对于其年龄而落后，身高增长也减慢了。
• 头痛、潮热和疲劳等预期的副作用很常见；38%的人在15至24个月后的访谈中说自己精力不足。
• 44人中有43人（98%）继续使用跨性别激素，这与荷兰的发现一致，即几乎没有人在使用阻断剂后停止。
• 在2年时数据中仍有24名年轻人，3年时有14名（3年时只有6人填写了自己的问卷），因此对于较长期的影响几乎无法下结论。
• McPherson和Freedman 2024年对同一数据的重新分析发现，根据测量指标、时间点和报告者的不同，15%至34%的年轻人明显变差。

Abstract

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.

Conclusion

Treatment with GnRHa was efficacious in suppressing pubertal progression; anticipated effects of sex-hormone withdrawal were common and there were no unexpected adverse events. BMD increased in the lumbar spine and was stable at the hip, while BMD z-scores fell, consistent with delayed puberty. Overall participant experience was positive, but the authors identified no changes in psychological function, quality of life or degree of gender dysphoria. The great majority went on to cross-sex hormones; one did not, which the authors took as evidence that gender identity development continues on GnRHa. Larger, longer-term studies using a range of designs are needed to quantify benefits and harms.