荷兰奠基性阻断剂研究：情绪改善但性别焦虑没有改善——无对照组，样本经过挑选

性别认同障碍青少年的青春期抑制：一项前瞻性随访研究

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

该研究追踪了2000至2008年间在阿姆斯特丹诊所被开具青春期阻断剂的111名青少年中最早的70人；在196名被转介的青少年中，有140人被判断适合医学治疗。
从首次就诊到开始使用跨性别激素之间，行为和情绪问题、抑郁以及临床医生评定的应对能力都有所改善。
根据家长的回答，处于需要临床帮助范围内的青少年比例从44%降至22%。
在青春期暂停期间，性别痛苦、对自己身体的感受以及一般的焦虑和愤怒没有变化。
没有青少年停用阻断剂，全部70人都继续使用跨性别激素，因此每一次“暂停”之后都是医学过渡。
没有对照组，因此这些变化无法与成长、每名青少年得到的心理支持，或人们自然从低谷中恢复区分开来。
这一群体经过了心理稳定和家庭支持方面的筛选，与如今的转介者非常不同，如今的转介者更多是痛苦始于青春期的女孩，且常伴有其他心理健康问题。
英格兰NICE的证据评估（2020年）将这项研究的发现评为非常薄弱的证据，但它却成为国际指南的基石。

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