荷蘭奠基性阻斷劑研究：情緒改善但性別焦慮沒有改善——無對照組，樣本經過挑選

性別認同障礙青少年的青春期抑制：一項前瞻性追蹤研究

Authors: Annelou L.C. de Vries, Thomas D. Steensma, Theo A.H. Doreleijers, Peggy T. Cohen-Kettenis
Journal: The Journal of Sexual Medicine
Year: 2011
Source: https://doi.org/10.1111/j.1743-6109.2010.01943.x

Summary

This was the first published study of the "Dutch protocol", the model that spread puberty blockers for teens with gender distress around the world. Amsterdam clinic researchers compared questionnaire scores of the first 70 teens given blockers, when they first came to the clinic and again just before cross-sex hormones. Behaviour problems and depression scores went down and clinicians rated them as coping better. But gender distress, feelings about their body, anxiety and anger did not change, and every teen went on to cross-sex hormones. The authors concluded blockers are a valuable option. But there was no comparison group, teens were picked for being stable with supportive families, and all got ongoing psychological care. So the study cannot show the blockers caused the improvements. England's health evidence body (NICE) rated its evidence as very weak in 2020.

Key findings

研究追蹤了 2000 至 2008 年間在阿姆斯特丹門診被開立青春期阻斷劑的 111 名青少年中的前 70 人；被轉介的 196 名青少年中有 140 人被判定適合醫療處置。
從首次門診到開始使用跨性別荷爾蒙之間，行為和情緒問題、憂鬱以及臨床人員評定的應對能力都有改善。
家長的回答顯示落在需要臨床協助範圍內的青少年比例，從 44% 降至 22%。
在青春期暫停期間，性別困擾、對身體的感受，以及一般的焦慮和憤怒都沒有改變。
沒有青少年停用阻斷劑，全部 70 人都接續使用跨性別荷爾蒙，因此這個「暫停」每次之後都接著醫療過渡。
沒有對照組，因此這些改變無法與成長、每位青少年所得到的心理支持，或人們從低潮中自然恢復區分開來。
這個群體經過心理穩定性和家庭支持度的篩選，與今天的轉介者非常不同，今天的轉介者更常是在青春期才開始出現困擾的女孩，且常有其他心理健康問題。
英格蘭 NICE 的證據審查（2020）將這項研究的發現評為非常薄弱的證據，但它卻成為國際指引的基石。

Abstract

INTRODUCTION: Puberty suppression by means of gonadotropin-releasing hormone analogues (GnRHa) is used for young transsexuals between 12 and 16 years of age. The purpose of this intervention is to relieve the suffering caused by the development of secondary sex characteristics and to provide time to make a balanced decision regarding actual gender reassignment. AIM: To compare psychological functioning and gender dysphoria before and after puberty suppression in gender dysphoric adolescents. METHODS: Of the first 70 eligible candidates who received puberty suppression between 2000 and 2008, psychological functioning and gender dysphoria were assessed twice: at T0, when attending the gender identity clinic, before the start of GnRHa; and at T1, shortly before the start of cross-sex hormone treatment. MAIN OUTCOME MEASURES: Behavioral and emotional problems (Child Behavior Checklist and the Youth-Self Report), depressive symptoms (Beck Depression Inventory), anxiety and anger (the Spielberger Trait Anxiety and Anger Scales), general functioning (the clinician's rated Children's Global Assessment Scale), gender dysphoria (the Utrecht Gender Dysphoria Scale), and body satisfaction (the Body Image Scale) were assessed. RESULTS: Behavioral and emotional problems and depressive symptoms decreased, while general functioning improved significantly during puberty suppression. Feelings of anxiety and anger did not change between T0 and T1. While changes over time were equal for both sexes, compared with natal males, natal females were older when they started puberty suppression and showed more problem behavior at both T0 and T1. Gender dysphoria and body satisfaction did not change between T0 and T1. No adolescent withdrew from puberty suppression, and all started cross-sex hormone treatment, the first step of actual gender reassignment. CONCLUSION: Puberty suppression may be considered a valuable contribution in the clinical management of gender dysphoria in adolescents.

Conclusion

Puberty suppression may be considered a valuable contribution in the clinical management of gender dysphoria in adolescents. The authors report that behavioural and emotional problems and depressive symptoms decreased and general functioning improved during puberty suppression, while gender dysphoria and body satisfaction did not change, and that no adolescent withdrew from puberty suppression — all went on to start cross-sex hormones.

Methodological limitations

No comparison group: Teens were only compared with themselves before treatment. So improvements could be due to growing up, time passing, people naturally drifting back from a bad patch, or the therapy given alongside, not the blockers. NICE's 2020 evidence review rated all its results as very weak evidence.
Therapy at the same time: All teens got ongoing psychological support from the gender team while on blockers. Abbruzzese, Levine and Mason (2023, Journal of Sex & Marital Therapy) point out this makes the drug's own effect impossible to separate.
Carefully chosen teens: Only 140 of 196 referred teens were judged suitable. They had to have had gender distress all their lives that got worse in puberty, be mentally stable without serious other conditions, and have a supportive home. So the study looks at a pre-screened group most likely to do well.
Small group and missing data: Only 70 of the 111 teens given blockers in this period were studied, and for some measures (such as gender distress and anger) data were available for only about 41 teens, according to NICE's re-analysis.
The main problem did not improve: Gender distress and body image, the very problems blockers are meant to ease, did not change, and nor did anxiety or anger. The benefits reported were on general behaviour and mood.
Most were not very distressed to start with: Average scores for behaviour and depression were mostly in the normal range at the start, so the reported drops are small shifts within normal levels, not recovery from severe distress.
Timing of questionnaires: The first questionnaires came at the first clinic visit, and the second just before cross-sex hormones, when teens had been approved for the next step they wanted. That approval may itself have made them feel better.
No real "time to think": Every teen went on to cross-sex hormones, so the study cannot support the idea that blockers give neutral time to decide. It fits just as well with blockers locking in a path to transition.
Short follow-up: Results were measured only until cross-sex hormones began. Longer-term effects on bones, brain development, fertility and sex life were not checked.
Later follow-up left people out: The 2014 follow-up of this group (in Pediatrics) reported on 55 of the 70. Those missing included three refused surgery because of diabetes or obesity and one who died of a severe infection after genital surgery. Critics (Abbruzzese et al., 2023) argue these gaps tilted the results toward good cases.
May not apply today: Most of these teens had gender distress from early childhood, many were born male, and all were treated under strict Dutch rules. The authors' later work and critics note this group does not match today's patients, who are mostly born female, started feeling distress in adolescence, and often have other conditions.
Clinic studying its own treatment: The authors worked at the clinic that created and delivered the Dutch protocol and judged their own treatment, with no independent check of the results.

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Summary

Key findings

Abstract

Conclusion