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

• הצוות חיפש בארבעה מאגרי מחקר מרכזיים מחקרים שפורסמו בין יולי 2020 לספטמבר 2023, באמצעות אותן שאלות ותוצאות ש-NICE השתמש בהן ב-2020: דיספוריה, בריאות נפשית, איכות חיים, דימוי גוף ותפקוד יומיומי.
• אף מחקר חדש של חוסמי התבגרות שפורסם מאז לא עמד בסטנדרטים של NICE עבור אף אחת מהתוצאות העיקריות.
• רק שני מחקרי הורמונים חדשים של המין השני עמדו בקריטריונים: מחקר סריקת מוח אחד שהשווה 19 בנים טרנס על טסטוסטרון ל-23 שאינם עליו, ומחקר דומה שני. שניהם היו קטנים, כללו רק בנים טרנס, ודורגו באיכות נמוכה.
• עוד 29 מחקרי הורמונים ו-25 סקירות נמצאו אך הושמטו, בעיקר מפני שלא השוו צעירים שטופלו לצעירים שלא טופלו.
• המחברים בדקו מחדש 12 מחקרים שמבקרים אמרו ש-NICE השמיט בטעות, והסכימו עם NICE. מחקרים אלה לא שאלו שאלת השוואה ברורה, לא דיווחו תוצאות חוסמים בנפרד, או עשו שימוש חוזר בקבוצות מטופלים שכבר נחקרו.
• המחברים מסיקים שהראיות הנוכחיות אינן מראות שדיספוריה מגדרית או בריאות נפשית משתפרות הרבה עם חוסמים או הורמונים, ושחסרים מחקרים ארוכי טווח.
• הם ממליצים על טיפול שיחתי להקלת המצוקה. כל שימוש בחוסמים או בהורמונים צריך לבוא אחרי הערכה יסודית וטיפול בבעיות בריאות נפשית אחרות, ולהתקיים במסגרת מחקר, כמו באנגליה.

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.