Johns Hopkins per la WPATH: gli ormoni «possono» migliorare umore e qualità di vita, ma tutte le prove erano deboli

Terapia ormonale, salute mentale e qualità della vita nelle persone transgender: una revisione sistematica

Revisioni sistematiche e delle evidenze Ormoni cross-sex Salute mentale e suicidio

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

La revisione ha incluso 20 studi in 22 articoli. Solo uno era uno studio randomizzato; la maggior parte seguiva gruppi di pazienti nel tempo e quattro erano istantanee di un singolo momento.
La maggior parte degli studi aveva meno di 60 persone, tutte provenienti da cliniche specialistiche per il genere. Otto dei 20 provenivano dall'Italia e solo 3 esaminavano gli adolescenti.
Gli ormoni erano associati a una migliore qualità della vita (7 studi), a meno depressione (12 studi) e a meno ansia (8 studi), ma diversi studi non hanno trovato alcun cambiamento.
I revisori hanno giudicato di bassa qualità le prove su qualità della vita, depressione e ansia, e non hanno potuto trarre alcuna conclusione sul suicidio.
L'unico studio sul suicidio, della clinica di Amsterdam, ha trovato che le donne trans sono morte per suicidio a un tasso 5,7 volte superiore a quello della popolazione generale. I revisori lo hanno giudicato a grave rischio di distorsione.
Nel gruppo di adolescenti olandesi, la depressione è migliorata durante i bloccanti della pubertà (farmaci che mettono in pausa la pubertà), ma dopo i successivi ormoni cross-sex il miglioramento complessivo rispetto all'inizio non era più chiaro.
La WPATH ha commissionato e pagato in parte la revisione per orientare le proprie linee guida di trattamento.
Documenti giudiziari resi pubblici nel 2024 suggeriscono che la WPATH abbia cercato di ottenere il diritto di approvare gli articoli del gruppo Hopkins e che questo sia stato l'unico articolo pubblicato dopo l'introduzione di tale regola da parte della WPATH.

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