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

• チームは、2020年7月から2023年9月に発表された研究について、4つの主要な研究データベースを検索し、NICEが2020年に用いたのと同じ問いと結果、すなわち違和感、メンタルヘルス、生活の質、身体像、日常の機能を用いました。
• NICEの基準を満たす新しい思春期ブロッカーの研究は、主要な結果のいずれについても、発表されていませんでした。
• 基準を満たした新しい異性ホルモンの研究は2件だけでした。テストステロンを使うトランス男子19人と使わない23人を比較した脳スキャン研究と、同様の2件目です。どちらも小規模で、トランス男子のみを含み、低い品質と評価されました。
• 他に29件のホルモンの研究と25件のレビューが見つかりましたが、主に治療を受けた若者と受けていない若者を比較していなかったため、除外されました。
• 著者らは、批判者がNICEは誤って除外したと主張した12件の研究を再確認し、NICEに同意しました。これらの研究は、明確な比較の問いを立てていなかったか、ブロッカーの結果を別に報告していなかったか、すでに研究された患者のグループを再利用していました。
• 著者らは、ブロッカーやホルモンで性別違和やメンタルヘルスが大きく改善することを現在のエビデンスは示しておらず、長期的な研究が欠けていると結論づけています。
• 苦痛を和らげるために心理療法を勧めています。ブロッカーやホルモンの使用は、徹底した評価と他のメンタルヘルスの問題の治療の後に、イングランドのように研究の中で行うべきだとしています。

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.