Johns Hopkins-review voor WPATH: hormonen 'kunnen' stemming verbeteren, maar al het bewijs was van lage sterkte

Hormoontherapie, geestelijke gezondheid en kwaliteit van leven bij transgenders: een systematische review

Systematische & evidence reviews Cross-sekse hormonen Geestelijke gezondheid & zelfmoord

Authors: Kellan E. Baker, Lisa M. Wilson, Ritu Sharma, Vadim Dukhanin, Kristen McArthur, Karen A. Robinson
Journal: Journal of the Endocrine Society
Year: 2021
Source: https://doi.org/10.1210/jendso/bvab011

Summary

WPATH, the main international trans health body, part-funded Johns Hopkins to review the evidence for its 2022 treatment guidelines. The reviewers found 20 studies, mostly small European clinic studies. These reported better quality of life and less depression and anxiety after starting hormones, and none reported harm to mental health. But the reviewers rated every conclusion as low-quality evidence, because of biased study designs, small numbers and the effects of surgery being mixed in. Only one study looked at suicide, so no conclusion was possible. The authors still called hormones 'essential' care, a stronger claim than their own ratings support. Court documents released in 2024 showed WPATH tried to control what the Hopkins team could publish. This was the only review published after WPATH brought in an approval rule. It shows weak evidence, not proven benefits.

Key findings

De review omvatte 20 studies in 22 artikelen. Slechts één was een gerandomiseerd onderzoek; de meeste volgden groepen patiënten in de tijd, en vier waren eenmalige momentopnamen.
De meeste studies hadden minder dan 60 mensen, allemaal uit gespecialiseerde genderklinieken. Acht van de 20 kwamen uit Italië, en slechts 3 keken naar tieners.
Hormonen hingen samen met een betere kwaliteit van leven (7 studies), minder depressie (12 studies) en minder angst (8 studies), maar verschillende studies vonden geen verandering.
De beoordelaars beoordeelden het bewijs als lage kwaliteit voor kwaliteit van leven, depressie en angst, en konden geen conclusie trekken over suïcide.
De enige suïcidestudie, van de kliniek in Amsterdam, vond dat transvrouwen 5,7 keer zo vaak door suïcide overleden als de algemene bevolking. De beoordelaars achtten haar ernstig risicovol voor vertekening.
In de Nederlandse tienergroep verbeterde depressie tijdens puberteitsblokkers (medicijnen die de puberteit onderbreken), maar na latere cross-sex hormonen was de algehele verbetering vanaf het begin niet meer duidelijk.
WPATH bestelde en betaalde deels voor de review om haar behandelrichtlijnen te onderbouwen.
Rechtbankdocumenten die in 2024 werden vrijgegeven suggereren dat WPATH het recht zocht om de artikelen van het Hopkins-team goed te keuren, en dat dit het enige artikel was dat werd gepubliceerd nadat WPATH die regel invoerde.

Abstract

We sought to systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people. We searched PubMed, Embase, and PsycINFO through June 10, 2020 for studies evaluating quality of life (QOL), depression, anxiety, and death by suicide in the context of gender-affirming hormone therapy among transgender people of any age. We excluded case studies and studies reporting on less than 3 months of follow-up. We included 20 studies reported in 22 publications. Fifteen were trials or prospective cohorts, one was a retrospective cohort, and 4 were cross-sectional. Seven assessed QOL, 12 assessed depression, 8 assessed anxiety, and 1 assessed death by suicide. Three studies included trans-feminine people only; 7 included trans-masculine people only, and 10 included both. Three studies focused on adolescents. Hormone therapy was associated with increased QOL, decreased depression, and decreased anxiety. Associations were similar across gender identity and age. Certainty in this conclusion is limited by high risk of bias in study designs, small sample sizes, and confounding with other interventions. We could not draw any conclusions about death by suicide. Future studies should investigate the psychological benefits of hormone therapy among larger and more diverse groups of transgender people using study designs that more effectively isolate the effects of hormone treatment.

Conclusion

Hormone therapy was associated with increased QOL, decreased depression, and decreased anxiety, with similar associations across gender identity and age. Certainty in this conclusion is limited by high risk of bias in study designs, small sample sizes, and confounding with other interventions; the strength of evidence for each outcome was graded low. No conclusions could be drawn about death by suicide. Despite these limitations, the authors stated that hormone therapy is likely associated with improvements in QOL, depression and anxiety, that no study showed harm to mental health, and that these benefits make hormone therapy 'an essential component of care'. They called for larger, more diverse studies using designs that better isolate the effects of hormones.

Methodological limitations

No comparison with untreated people: Almost no study compared people on hormones with similar people not on them. The one randomised trial compared different testosterone doses in trans men, so it cannot show hormones versus no hormones.
Low-quality evidence throughout: The authors themselves rated the evidence low for every result they could assess, and too thin to judge for suicide. Their closing claim that hormones are 'essential' goes beyond their own ratings.
Mixed up with surgery and other care: Many studies looked at hormones and surgery together, or did not say who had surgery. Counselling was often required or offered alongside hormones, so the effect of hormones alone cannot be separated out.
Small groups from specialist clinics only: Most studies had fewer than 60 people, all from specialist clinics with strict entry rules. Results may not apply to people who get hormones with little assessment or through online prescribing.
Doctors were also gatekeepers: The authors note that the same clinicians decided who got treatment and ran the research. Patients may have overstated or played down symptoms to get treatment, and may have felt unable to refuse taking part.
Different and untested measures: Studies used many different questionnaires, some untested (one used a 4-point depression question where the typical starting answer was 'not at all depressed'). None had been tested in trans people, and results could not be combined.
Mixed and 'no change' results: Several studies found no change in quality of life, depression or anxiety. In the Dutch teenage group, the improvement in depression during blockers was no longer clear after cross-sex hormones.
Suicide question can't be answered: Only one study, looking back at records, reported suicide deaths. It found trans women died by suicide at 5.7 times the general population rate. The review could not say whether hormones affect suicide.
Short follow-up and dropouts ignored: Studies needed only 3 months of follow-up, and the review did not consistently report how many people dropped out, which is often high in gender clinic studies.
Funder influence: WPATH partly paid for the review and set the question. Court documents released in 2024 (Boe v. Marshall, reported by The Economist) show WPATH sought the right to approve or block the team's papers. A WPATH form for this paper records a WPATH person's part in 'design, drafting of the article and final approval'. This contradicts the paper's statement that WPATH had no role in design, analysis or writing.
Other reviews may have been held back: The Hopkins team reportedly gave WPATH material for several reviews, but this is the only one published after WPATH's 2020 approval rule. So the full evidence the project produced is not public.
Missing studies: The authors admit studies with unwelcome results may not have been published, studies outside journals may have been missed, and some relevant studies were left out for not reporting the type or length of treatment.

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Summary

Key findings

Abstract

Conclusion