Nghiên cứu thuốc chặn dậy thì của Tavistock không thấy lợi ích tâm lý, nhưng 98% vẫn chuyển sang hormone khác giới

Kết quả ngắn hạn của việc ức chế dậy thì trong một nhóm chọn lọc thanh thiếu niên 12 đến 15 tuổi bị khủng hoảng giới tính dai dẳng ở Anh

Nghiên cứu thuần tập & sổ bộ Thuốc ức chế dậy thì Sức khỏe tâm thần & tự sát

Authors: Polly Carmichael, Gary Butler, Una Masic, Tim J. Cole, Bianca L. De Stavola, Sarah Davidson, Elin M. Skageberg, Sophie Khadr, Russell M. Viner
Journal: PLOS ONE
Year: 2021
Source: https://doi.org/10.1371/journal.pone.0243894

Summary

This was the UK's own test of puberty blockers, run by the Tavistock's gender clinic for children from 2011. Forty-four carefully chosen 12–15-year-olds were given a blocker drug and followed until they were over 16. The blockers paused puberty as intended. But there was no measurable change in emotional distress, self-harm, quality of life or gender distress, and bone density fell behind other teens their age. Most young people spoke positively about the treatment in interviews, and 43 of 44 went on to cross-sex hormones. The authors call for larger studies. There was no comparison group, numbers fell sharply after the first year, and a later re-analysis found up to a third got worse. So the study offers no evidence that blockers help mental health.

Key findings

44 người trẻ từ 12–15 tuổi (25 người sinh ra là nam, 19 người sinh ra là nữ) có phiền muộn giới nghiêm trọng, kéo dài đã bắt đầu dùng thuốc chặn dậy thì trong khoảng 2011 đến 2015, sau thời gian đánh giá điển hình hai năm tại phòng khám.
Cả cha mẹ lẫn những người trẻ đều không báo cáo thay đổi nào về các vấn đề cảm xúc hoặc hành vi, hay về tự làm hại bản thân, sau 1, 2 hoặc 3 năm.
Chất lượng cuộc sống, cảm xúc về cơ thể, phiền muộn giới và mức độ đối phó (theo đánh giá của bác sĩ lâm sàng) cũng thay đổi ít; các tác giả lưu ý thuốc chặn không thay đổi cơ thể theo hướng giới tính mong muốn.
Mật độ xương ở lưng dưới phát triển chậm hơn so với các thiếu niên khác, nên tụt lại so với tuổi của họ, và tăng trưởng chiều cao cũng chậm lại.
Các tác dụng phụ dự kiến như đau đầu, bốc hỏa và mệt mỏi là phổ biến; 38% nói trong các cuộc phỏng vấn sau 15–24 tháng rằng họ thiếu năng lượng.
43 trong 44 người (98%) tiếp tục dùng hormone khác giới, khớp với phát hiện của Hà Lan rằng hầu như không ai ngừng sau thuốc chặn.
Chỉ còn 24 người trẻ trong dữ liệu ở năm thứ 2 và 14 người ở năm thứ 3 (chỉ 6 người tự điền bảng câu hỏi ở năm thứ 3), nên có thể nói rất ít về tác động lâu dài hơn.
Một phân tích lại năm 2024 của McPherson và Freedman trên cùng dữ liệu cho thấy 15–34% người trẻ rõ ràng trở nên tệ hơn, tùy theo thước đo, thời điểm và người báo cáo.

Abstract

BACKGROUND: In adolescents with severe and persistent gender dysphoria (GD), gonadotropin releasing hormone analogues (GnRHa) are used from early/middle puberty with the aim of delaying irreversible and unwanted pubertal body changes. Evidence of outcomes of pubertal suppression in GD is limited. METHODS: We undertook an uncontrolled prospective observational study of GnRHa as monotherapy in 44 12-15 year olds with persistent and severe GD. Prespecified analyses were limited to key outcomes: bone mineral content (BMC) and bone mineral density (BMD); Child Behaviour CheckList (CBCL) total t-score; Youth Self-Report (YSR) total t-score; CBCL and YSR self-harm indices; at 12, 24 and 36 months. Semistructured interviews were conducted on GnRHa. RESULTS: 44 patients had data at 12 months follow-up, 24 at 24 months and 14 at 36 months. All had normal karyotype and endocrinology consistent with birth-registered sex. All achieved suppression of gonadotropins by 6 months. At the end of the study one ceased GnRHa and 43 (98%) elected to start cross-sex hormones. There was no change from baseline in spine BMD at 12 months nor in hip BMD at 24 and 36 months, but at 24 months lumbar spine BMC and BMD were higher than at baseline (BMC +6.0 (95% CI: 4.0, 7.9); BMD +0.05 (0.03, 0.07)). There were no changes from baseline to 12 or 24 months in CBCL or YSR total t-scores or for CBCL or YSR self-harm indices, nor for CBCL total t-score or self-harm index at 36 months. Most participants reported positive or a mixture of positive and negative life changes on GnRHa. Anticipated adverse events were common. CONCLUSIONS: Overall patient experience of changes on GnRHa treatment was positive. We identified no changes in psychological function. Changes in BMD were consistent with suppression of growth. Larger and longer-term prospective studies using a range of designs are needed to more fully quantify the benefits and harms of pubertal suppression in GD.

Conclusion

Treatment with GnRHa was efficacious in suppressing pubertal progression; anticipated effects of sex-hormone withdrawal were common and there were no unexpected adverse events. BMD increased in the lumbar spine and was stable at the hip, while BMD z-scores fell, consistent with delayed puberty. Overall participant experience was positive, but the authors identified no changes in psychological function, quality of life or degree of gender dysphoria. The great majority went on to cross-sex hormones; one did not, which the authors took as evidence that gender identity development continues on GnRHa. Larger, longer-term studies using a range of designs are needed to quantify benefits and harms.

Methodological limitations

No comparison group: The authors admit that without a comparison group they cannot say what caused what. Mental health, self-harm and bone density all change naturally during the teenage years, so "no change" cannot be read as either benefit or harm.
Small and shrinking group: Only 44 young people took part. Data were available for 24 at 2 years and 14 at 3 years, and the young people's own questionnaires for just 15 at 2 years and 6 at 3 years. With so few, real changes could easily be missed.
Carefully chosen group: To take part, children had to have felt the other gender all their lives, be mentally stable, have no serious mental illness and have had at least six months of assessment. So the results do not apply to most children the clinic saw at the time.
Therapy at the same time: Regular psychological support was required, and local services treated other problems. So any effect of the drug is mixed up with the effect of therapy.
Averages hide people who got worse: A re-analysis of the study's data (McPherson & Freedman, 2024, Journal of Sex & Marital Therapy) found 15–34% clearly got worse, and the number who clearly improved fell toward zero over time.
Published late, and disputed: The study began in 2011 but was not published in a journal until 2021. Michael Biggs had earlier pointed to unpublished 2015 early results suggesting more self-harm and problems in girls; the authors say those data were incomplete and not yet checked.
Problems with the data: The authors report young people got tired of questionnaires, some refused later follow-ups, missing answers made some data unusable, and some detailed data were lost when hospital computer systems changed.
Measures dropped partway: Planned questionnaires on gender distress and a teacher questionnaire were dropped during the study, so fewer things were measured than intended.
Interview findings not tested: The finding that young people had a "positive experience" comes from simple interviews, with nothing to compare against from before treatment, written up in clinic notes rather than using tested questionnaires.
Almost everyone moved on to hormones: With 98% going on to cross-sex hormones, the study gives no support to the idea that blockers are a neutral pause. It cannot tell whether this was due to who was chosen or to the blockers themselves.
Clinic studying its own treatment: The study had no outside funding, was run inside the clinic, and was led by the clinic's director, whose service gave the treatment being tested.

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Summary

Key findings

Abstract

Conclusion