Étude néerlandaise fondatrice sur les bloqueurs : humeur améliorée, pas la dysphorie — sans témoins, échantillon trié

Suppression pubertaire chez des adolescents atteints de trouble de l'identité de genre : une étude de suivi prospective

Études de cohorte & registres Bloqueurs de puberté Santé mentale & suicide

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

L'étude a suivi les 70 premiers des 111 adolescents à qui l'on a prescrit des bloqueurs de puberté à la clinique d'Amsterdam entre 2000 et 2008 ; 140 des 196 adolescents adressés avaient été jugés aptes à un traitement médical.
Les problèmes de comportement et émotionnels, la dépression et la capacité à faire face évaluée par les cliniciens se sont tous améliorés entre la première consultation à la clinique et le début des hormones du sexe opposé.
La proportion d'adolescents dont les réponses des parents les plaçaient dans la zone nécessitant une aide clinique est passée de 44 % à 22 %.
La détresse de genre, le ressenti sur leur corps, et l'anxiété et la colère générales n'ont pas changé pendant la mise en pause de la puberté.
Aucun adolescent n'a arrêté les bloqueurs et les 70 sont passés aux hormones du sexe opposé ; la « pause » a donc été suivie d'une transition médicale à chaque fois.
Il n'y avait pas de groupe de comparaison ; les changements ne peuvent donc pas être distingués de la croissance, du soutien psychologique reçu par chaque adolescent, ou du retour naturel d'une mauvaise passe.
Le groupe avait été sélectionné pour sa stabilité mentale et des familles bienveillantes, et diffère beaucoup des orientations d'aujourd'hui, plus souvent des filles dont la détresse a commencé à l'adolescence et qui ont souvent d'autres problèmes de santé mentale.
La revue de preuves du NICE anglais (2020) a jugé les résultats de cette étude comme des preuves très faibles, et pourtant elle est devenue une pierre angulaire des recommandations internationales.

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