Summary

In 2020 England's NICE found the evidence on puberty blockers and cross-sex hormones for under-18s with gender dysphoria to be of very low quality. This German team repeated NICE's search method for studies published from July 2020 to September 2023. No new puberty-blocker study met NICE's standards. Only two small hormone studies qualified. Both were brain-scan studies of trans boys, not designed to test whether treatment helps, and both were rated low quality. Many other studies were left out because they had no comparison group. The authors conclude the evidence does not show that dysphoria or mental health improve much with treatment. They suggest talking therapy for distress, and say any hormone treatment should happen within research. This matches other reviews. But the 'no new studies' result depends on strict rules, and several authors had publicly opposed Germany's guideline.

Key findings

• 研究团队在四个主要研究数据库中检索了2020年7月至2023年9月发表的研究，使用的问题和结局与NICE在2020年使用的相同：焦虑、心理健康、生活质量、身体形象和日常功能。
• 自NICE以来发表的新的青春期阻断剂研究，没有任何一项在任何主要结局上达到其标准。
• 只有两项新的跨性别激素研究合格：一项脑部扫描研究，比较了19名使用睾酮的跨性别男孩与23名未使用者，以及另一项类似研究。两项研究规模都小，只包括跨性别男孩，并被评为低质量。
• 另外发现的29项激素研究和25篇综述被排除，主要是因为它们没有将接受治疗的年轻人与未接受治疗者作比较。
• 作者重新检查了批评者说NICE错误排除的12项研究，并同意NICE的做法。这些研究没有提出明确的比较问题，没有单独报告阻断剂的结果，或重复使用了已研究过的患者群体。
• 作者的结论是，目前的证据没有表明阻断剂或激素能使性别焦虑或心理健康有明显改善，并且缺少长期研究。
• 他们建议用谈话治疗缓解痛苦。任何阻断剂或激素的使用都应在彻底评估并治疗其他心理健康问题之后，并像英格兰那样在研究中进行。

Abstract

Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria Abstract: Objective: The suppression of physiological puberty using puberty-blocking pharmacological agents (PB) and prescribing cross-sex hormones (CSH) to minors with gender dysphoria (GD) is a current matter of discussion, and in some cases, PB and CSH are used in clinical practice for this particular population. Two systematic reviews (one on PB, one on CSH treatment) by the British National Institute for Clinical Excellence (NICE) from 2020 indicated no clear clinical benefit of such treatments regarding critical outcome variables. In particular, these two systematic NICE reviews on the use of PB and CSH in minors with GD detected no clear improvements of GD symptoms. Moreover, the overall scientific quality of the available evidence, as discussed within the above-mentioned two NICE reviews, was classified as "very low certainty" regarding modified GRADE criteria. Method: The present systematic review presents an updated literature search on this particular topic (use of PB and CSH in minors with GD) following NICE principles and PICO criteria for all relevant new original research studies published since the release of the two above-mentioned NICE reviews (updated literature search period was July 2020-August 2023). Results: The newly conducted literature search revealed no newly published original studies targeting NICE-defined critical and important outcomes and the related use of PB in minors with GD following PICO criteria. For CSH treatment, we found two new studies that met PICO criteria, but these particular two studies had low participant numbers, yielded no significant additional clear evidence for specific and clearly beneficial effects of CSH in minors with GD, and could be classified as "low certainty" tfollowing modified GRADE criteria. Conclusions: The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data. The electronic supplement (ESM) 1 is an adapted and abreviated English version of this work.

Conclusion

The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data.