OPS Spotlight - Ethical care requires a synthesis of the best available evidence
- La Petite Sirène
- Jun 26
- 5 min read
By Beryl Koener, member of the PAHO Board, doctor of medicine, child and adolescent psychiatrist and doctor of neuropsychopharmacology
Ethical care requires a synthesis of the best available evidence
Moti Gorin, Chan Kulatunga-Moruzi, Ari R. Joffe & J. Cohn
Pages 73-76 | Published online : 06 June 2025 - The American Journal of Bioethics - Volume 25, 2025
Context
This article revisits the basic ethical principles to be followed—autonomy, justice, beneficence, and non-maleficence—in light of the international systematic literature reviews currently available on the use of puberty blockers (PB) and gender-affirming hormones (GAH). It responds to the assertions made by Kirby [1], who invokes these same ethical principles, but without grounding them in evidence-based medicine (EBM), instead relying on a handpicked selection of studies.
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Introduction
• Well-conducted systematic reviews are the foundation of evidence-based medicine.
• Systematic reviews also form the basis for reliable clinical guidelines.
• Umbrella reviews [2] synthesize systematic reviews in a rigorous and structured way.
State of the Evidence in Pediatric Gender Medicine Today
• Numerous recent systematic literature reviews on gender transition in pediatric populations—following the Cass Review (on puberty blockers, hormones, and surgery)—have all reached the same conclusion: the evidence regarding the benefits of these treatments is of low to very low certainty. According to the GRADE classification, this corresponds to limited or very low confidence that the true effect is close to the estimated effect. [3]
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Kirby’s Ethical Analysis
• Omits important scientific advances (i.e., data from systematic reviews), like most critiques of the Cass Review. Instead, it relies on a small, highly selective sample of inconclusive and sometimes outdated studies (many of which were already included in the systematic reviews) to claim an “improvement in mental functioning and well-being.”
• Claims that only a small number of patients detransition,
→ yet systematic literature reviews indicate that the global rate of detransition remains unknown due to a lack of adequate follow-up.
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A Mischaracterization of the Debate as Merely Political
• Kirby claims that policy shifts in Finland, Sweden, and the UK were due to “a dominant wave of political opposition.”
→ This is incorrect: Finland, Sweden, and the UK published updated, more cautious recommendations based on rigorous systematic reviews [4] of available data, with documented explanations.
• Kirby also asserts that parents who express reservations about their children’s transitions are influenced by conservative right-wing movements, omitting the possibility that these parents may simply be well-informed about the available evidence.
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Reliable Guidelines
• Kirby claims that the only reliable care guidelines for gender-distressed youth are those of WPATH and the Endocrine Society.
→ However, systematic reviews of the literature analyzing all existing guidelines have shown that these are not based on evidence-based medicine. Furthermore, it was revealed that WPATH interfered with the production of systematic reviews, refusing to publish findings that did not align with its views.
→ Only the Swedish and Finnish guidelines are currently grounded in EBM.
→ Reliable guidelines must be based on systematic reviews of evidence and should “link the strength of recommendations to the quality of the underlying evidence.”
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Health Research Disinformation
• Kirby also refers to the “misunderstanding and/or intentional promotion of disinformation or misinformation regarding the nature and types of research that can and should inform gender-affirming care for youth.” He implies that critics demand randomized controlled trials (RCTs).
→ At no point does the Cass Review recommend RCTs as the only valid method for producing high-quality clinical studies. The Cass Review bases its recommendations on seven systematic literature reviews, four additional reviews, and input from all stakeholder groups, including patients and parents (Cass 2024).
• Kirby’s criticisms of the Cass Review rely on a Yale School critique—an unpeer-reviewed essay containing numerous inaccuracies and unsubstantiated claims, already addressed in peer-reviewed responses (Cheung et al. 2025; McDeavitt et al. 2025).
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Conclusions
The current state of evidence from systematic reviews challenges Kirby’s ethical analysis in support of gender affirmation in minors.
• First, it is incorrect to claim that the evidence supports a favorable risk-benefit ratio for hormonal or surgical interventions in the treatment of gender dysphoria in children. Therefore, offering and administering these interventions to adolescents is incompatible with clinicians’ duties of non-maleficence and beneficence.
• Second, while Kirby is certainly right that clinicians have a duty to respect patient autonomy, this does not imply a duty to offer interventions lacking a favorable risk-benefit profile. On the contrary, clinicians have a duty to refrain from providing treatments whose expected benefits are not proportional to the potential risks. (See the recent article by Kingdon et al. [5] for a thorough analysis.)
• Finally, while it is unjust to deprive vulnerable patients of beneficial, evidence-based treatments, it is equally unjust to offer and provide interventions whose risks outweigh their benefits—especially when alternative therapies exist.
[1] Kirby, J. 2025. A multi-lens ethics analysis of gender-affirming care for youth with implications for practice and policy. The American Journal of Bioethics 25 (6):57–72. doi: 10.1080/15265161.2025.2497983.
[2] telles que celles de Brignardello-Petersen et Wiercioch (2022) sur la question de la médication dans le cadre de la dysphorie de genre chez les mineurs : Brignardello-Petersen, R., and W. Wiercioch. 2022. Effects of gender affirming therapies in people with gender dysphoria: Evaluation of the best available evidence. Agency for Health Care Administration Florida Medicaid Generally Accepted Professional Medical Standards Determination on the Treatment of Gender Dysphoria Attachment C. https://ahca.myflorida.com/ letkidsbekids/docs/AHCA_GAPMS_June_2022_ Attachment_C.pdf.
[3] Miroshnychenko, A., S. Ibrahim, Y. Roldan, C. Kulatunga-Moruzi, S. Montante, R. Couban, G. Guyatt, and R. Brignardello-Petersen. 2025a. Gender affirming hormone therapy for individuals with gender dysphoria aged <26 years: A systematic review and meta-analysis. Archives of Disease in Childhood doi: 10.1136/archdischild-2024-327921.
· Miroshnychenko, A., Y. Roldan, S. Ibrahim, C. Kulatunga-Moruzi, S. Montante, R. Couban, G. Guyatt, and R. Brignardello-Petersen. 2025b. Puberty blockers for gender dysphoria in youth: A systematic review and meta-analysis. Archives of Disease in Childhood. doi: 10.1136/archdischild-2024-327909.
· Miroshnychenko, A., Y. M. Roldan, S. Ibrahim, C. Kulatunga-Moruzi, K. Dahlin, S. Montante, R. Couban, G. Guyatt, and R. Brignardello-Petersen. 2024. Mastectomy for individuals with gender dysphoria below 26 years of age: A systematic review and meta-analysis. Plastic & Reconstructive Surgery. doi: 10.1097/PRS.0000000000011734.
· Brignardello-Petersen, R., and W. Wiercioch. 2022. Effects of gender affirming therapies in people with gender dysphoria: Evaluation of the best available evidence. Agency for Health Care Administration Florida Medicaid Generally Accepted Professional Medical Standards Determination on the Treatment of Gender Dysphoria Attachment C. https://ahca.myflorida.com/ letkidsbekids/docs/AHCA_GAPMS_June_2022_ Attachment_C.pdf.
[4] Pasternak, I., I. Söderström, M. Saijonkari, and M. Mäkelä. 2019. Lääketieteelliset menetelmät sukupuolivariaatioihin liit- tyvän dysforian hoidossa. Systemaattinen katsaus [Google translation: Medical approaches to the treatment of gender dysphoria. A systematic review.] Helsinki: Summaryx Ltd. https://palveluvalikoima.fi/documents/1237350/22895008/ Valmistelumuistion%20Liite%201.%20Kirjallisuuskatsaus. pdf/5ad0f362-8735-35cd-3e53-3d17a010f2b6/ Valmistelumuistion%20Liite%201.%20Kirjallisuuskatsaus.pdf.
· Cass, H. 2024. Independent review of gender identity services for children and young people: Final report. https:// webarchive.nationalarchives.gov.uk/ukgwa/20250310143933/ https://cass.independent-review.uk/home/publications/ final-report/.
· Block, J. 2023. Gender dysphoria in young people is ris- ing—and so is professional disagreement. British Medical Journal 380:382. doi: 10.1136/bmj.p382.
[5] Camilla Kingdon, Nicola Stingelin-Giles & Hilary Cass (2025) The Cass Review; Distinguishing Fact from Fiction, The American Journal of Bioethics, 25:6, 5-10, DOI: 10.1080/15265161.2025.2504397
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