Summary

This review collected every study it could find, up to September 2023, on puberty blockers for young people with gender distress, and rated how trustworthy the evidence was. Only 10 studies qualified, and none was a randomised trial, where people are assigned to treatment by chance. The studies were small and often missing results for many people. Every result on mental health, gender distress and bone density was rated very low quality. Bone density seemed lower after treatment, and nearly all young people went on to cross-sex hormones. The authors conclude we cannot tell whether blockers help or harm, and call for better studies. Its findings match other independent reviews, including those for England's Cass Review. But it was funded by SEGM, a group critical of youth transition, it only searched English-language studies, and it misses newer studies.

Key findings

• مرور 10 مطالعه یافت: 3 مطالعه جوانانی را که بلوکر مصرف کردند و نکردند مقایسه کردند و 7 مطالعه فقط همان افراد را پیش و پس سنجیدند.
• هیچ کارآزمایی تصادفی وجود نداشت، که در آن افراد به‌صورت شانسی به درمان اختصاص می‌یابند.
• همهٔ شواهد دربارهٔ ناراحتی جنسیتی، عملکرد روزانه و افسردگی بسیار کم‌کیفیت ارزیابی شد، پس نه فایده و نه آسیب را نمی‌توان رد کرد.
• در مطالعات مقایسه‌ای، نمرات عملکرد روزانه پس از 12 ماه با بلوکرها تا حدی بهتر به نظر می‌رسید، اما نتیجه چنان نامطمئن بود که می‌توانست از کمی بدتر تا بسیار بهتر را معنا دهد.
• تراکم استخوان در لگن و ستون فقرات پس از بلوکرها از همسالان عقب افتاد، هرچند این شواهد نیز بسیار ضعیف ارزیابی شد.
• در دو مطالعه، 92% جوانانی که بلوکر گرفتند ظرف 1 تا 3 سال به هورمون‌های جنس مخالف ادامه دادند.
• چند مطالعه نتایج کمتر از نیمی از جوانان را داشتند و هیچ‌کدام به‌درستی درمان گفتاری، سایر شرایط روانی یا حمایت خانواده را در نظر نگرفتند.
• نویسندگان خواستار مطالعات دقیقی هستند که جوانان را در زمان به‌جلو پیگیری کنند و، اگر اخلاقی باشد، کارآزمایی‌های تصادفی.

Abstract

Aim Gender dysphoria (GD) refers to the psychological distress associated with the incongruence between one's sex and one's gender identity. To manage GD, individuals may delay the development of primary and secondary sex characteristics with the use of puberty blockers. In this systematic review, we assess and summarise the certainty of the evidence about the effects of puberty blockers in individuals experiencing GD. Methods We searched Medline, Embase, PsychINFO, Social Sciences Abstracts, LGBTQ+ Source and Sociological Abstracts from inception to September 2023. We included observational studies comparing puberty blockers with no puberty blockers in individuals aged <26 years experiencing GD, as well as before-after and case series studies. Outcomes of interest included psychological and physical outcomes. Pairs of reviewers independently screened articles, abstracted data and assessed risk of bias. We performed a meta-analysis and assessed the certainty of a non-zero effect using the grading of recommendations assessment, development and evaluation (GRADE) approach. Results We included 10 studies. Comparative observational studies (n=3), comparing puberty blockers versus no puberty blockers, provided very low certainty of evidence on the outcomes of global function and depression. Before-after studies (n=7) provided very low certainty of evidence addressing gender dysphoria, global function, depression, and bone mineral density. Conclusions There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing GD. Methodologically rigorous prospective studies are needed to understand the effects of this intervention. Trial registration number PROSPERO CRD42023452171.

Conclusion

The best available evidence reporting the effects of puberty blockers in individuals with GD was mostly very low certainty and therefore we cannot exclude the possibility of benefit or harm. There was evidence available for the outcomes of global function, depression, GD, bone mineral density and progression to gender affirming hormone therapy. High certainty evidence from prospective cohort studies and, if ethical, RCTs, is needed to understand the short and long term effects of puberty blockers in individuals experiencing GD.