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

• 研究團隊在四個主要研究資料庫中檢索 2020 年 7 月至 2023 年 9 月發表的研究，使用與 NICE 在 2020 年相同的問題和結果：焦慮、心理健康、生活品質、身體形象和日常功能。
• 自 NICE 之後發表的新青春期阻斷劑研究，在任何主要結果上都沒有達到其標準。
• 只有兩項新的跨性別荷爾蒙研究符合：一項腦部掃描研究比較了 19 名使用睪固酮的跨性別男孩與 23 名未使用者，另一項類似的研究。兩者都規模小、只包含跨性別男孩，並被評為低品質。
• 另外找到 29 項荷爾蒙研究和 25 項回顧但被排除，主要是因為它們沒有比較接受治療與未接受治療的年輕人。
• 作者重新檢查了批評者認為 NICE 錯誤排除的 12 項研究，並同意 NICE 的判斷。這些研究沒有提出明確的比較問題、沒有單獨報告阻斷劑的結果，或重複使用已被研究過的患者群。
• 作者的結論是，目前的證據並未顯示阻斷劑或荷爾蒙能使性別焦慮或心理健康大幅改善，且缺乏長期研究。
• 他們建議以談話治療來減輕痛苦。任何使用阻斷劑或荷爾蒙的情況，都應在徹底評估並治療其他心理健康問題之後，並在研究中進行，就像英格蘭那樣。

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.