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

• 연구팀은 2020년 NICE가 쓴 것과 같은 질문과 결과(불쾌감, 정신 건강, 삶의 질, 신체상, 일상 기능)를 사용해, 2020년 7월부터 2023년 9월 사이에 발표된 연구를 주요 연구 데이터베이스 네 곳에서 검색했습니다.
• NICE 이후 발표된 새 사춘기 차단제 연구 중 어떤 주요 결과에서도 NICE의 기준을 충족한 것은 없었습니다.
• 새 반대 성 호르몬 연구는 두 건만 자격을 갖췄습니다. 테스토스테론을 쓰는 트랜스 남아 19명과 쓰지 않는 23명을 비교한 뇌 스캔 연구 한 건과 비슷한 두 번째 연구입니다. 둘 다 작았고 트랜스 남아만 포함했으며 낮은 품질로 평가되었습니다.
• 다른 호르몬 연구 29건과 검토 25건도 찾았지만, 주로 치료받은 청소년과 받지 않은 청소년을 비교하지 않았기 때문에 제외되었습니다.
• 저자들은 비판자들이 NICE가 잘못 제외했다고 주장한 연구 12건을 다시 확인했고 NICE에 동의했습니다. 이 연구들은 명확한 비교 질문을 하지 않았거나, 차단제 결과를 따로 보고하지 않았거나, 이미 연구된 환자 집단을 재사용했습니다.
• 저자들은 현재의 근거가 차단제나 호르몬으로 성별 불쾌감이나 정신 건강이 크게 좋아진다는 것을 보여주지 않으며 장기 연구가 없다고 결론짓습니다.
• 고통을 덜기 위한 대화 치료를 권고합니다. 차단제나 호르몬의 사용은 철저한 평가와 다른 정신 건강 문제의 치료 이후에, 잉글랜드처럼 연구 안에서 이루어져야 합니다.

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.