Endocrine Society stöder blockerare och hormoner för tonåringar – men bedömer själv evidensen som låg

Endokrin behandling av personer med könsdysfori/könsinkongruens: en klinisk riktlinje från Endocrine Society

Kommentarer & analyser Könshormoner Riktlinjer & policy

Authors: Wylie C. Hembree, Peggy T. Cohen-Kettenis, Louis Gooren, Sabine E. Hannema, Walter J. Meyer, M. Hassan Murad, Stephen M. Rosenthal, Joshua D. Safer, Vin Tangpricha, Guy G. T'Sjoen
Journal: Journal of Clinical Endocrinology & Metabolism
Year: 2017
Source: https://doi.org/10.1210/jc.2017-01658

Summary

This 2017 guideline from the Endocrine Society, a large body of hormone doctors, recommends puberty blockers for teens at the first signs of puberty, cross-sex hormones from about 16, and hormone plans with safety checks for adults. With WPATH's standards, it is often cited as proof that youth gender medicine is 'evidence-based'. Yet its own grading rates the evidence behind every teen recommendation as low or very low quality. Some are still strong recommendations, which Gordon Guyatt, co-founder of that grading system, called a 'serious problem'. Its commissioned reviews looked only at bone and heart safety, not at whether treatment eases distress or helps mental health. Several authors created the Dutch approach it relies on, and a York review for England's Cass Review rated it low quality. It reflects expert opinion more than strong evidence.

Key findings

Riktlinjen skrevs av en panel på nio experter, en metodexpert och en medicinsk skribent. Den medstöddes av WPATH och fem andra medicinska föreningar i USA och Europa.
Den avråder från hormonbehandling före puberteten, men rekommenderar pubertetsblockerare när tonåringar visar de första tecknen på pubertet (bröstknoppar eller testikeltillväxt).
Korskönshormoner kan läggas till när ett team av specialister bekräftar att lidandet har varat och tonåringen kan samtycka. Riktlinjen säger att de flesta tonåringar kan samtycka vid 16 och tillåter tidigare start, samtidigt som den noterar att det finns mycket lite publicerad erfarenhet före cirka 13,5 till 14.
Enligt dess egen gradering är evidensen bakom varje rekommendation för tonåringar av låg eller mycket låg kvalitet. Till exempel får pubertetsblockerare en stark rekommendation baserad på evidens av låg kvalitet.
De två evidensgranskningar som den beställde tittade bara på hormoners effekter på hjärta, kolesterol och skelett, inte på lidande, psykisk hälsa eller livskvalitet.
För bröstborttagning hos vuxna transmän säger den att det inte finns tillräckligt med evidens för att sätta en miniminivå för ålder, en svag rekommendation på evidens av mycket låg kvalitet.
Riktlinjen publicerade två rättelser 2018, och en uppdatering uppges vara på gång.

Abstract

OBJECTIVE: To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. PARTICIPANTS: The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS: Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. CONCLUSION: Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

Conclusion

The guideline concludes that gender affirmation is a multidisciplinary treatment in which endocrinologists play an important role. Hormone treatment is not recommended for prepubertal children. Adolescents who have entered puberty (Tanner stage G2/B2) and meet criteria should be treated with GnRH-agonist puberty suppression, and gender-affirming hormones may be added after a multidisciplinary team confirms persistent gender dysphoria and sufficient capacity to consent, which most adolescents have by age 16; there may be compelling reasons to start earlier, though published experience before 13.5–14 years is minimal. Adults should receive physiologic levels of gender-appropriate hormones with monitoring for known risks, and clinicians should avoid harming people with conditions other than gender dysphoria who may not benefit from the physical changes.

Methodological limitations

Weak evidence by its own grading: Every teen recommendation is rated low or very low quality evidence, including puberty blockers at the first signs of puberty and cross-sex hormones at about 16. The confidence the guideline suggests is not matched by its own evidence ratings.
Strong advice on weak evidence: Some statements, such as using puberty blockers, are worded 'we recommend' despite low-quality evidence. Gordon Guyatt, a co-founder of the grading system used, called this one of several 'serious problems' (BMJ 2023).
Reviews skipped the key question: The two commissioned reviews covered only bone, cholesterol and heart safety, not whether treatment eases gender distress, improves mental health or quality of life. Guyatt called the distress itself arguably 'the most important outcome'.
Rated low quality by an independent review: A University of York review of guidelines done for England's Cass Review (Taylor and others, Archives of Disease in Childhood 2024) found the Endocrine Society and WPATH guidelines 'lack developmental rigour'. It said they are linked by backing each other and form the basis for most other guidance.
WPATH links make it circular: WPATH co-backed the guideline, and four panel members (Rosenthal, Safer, Tangpricha, T'Sjoen) also wrote WPATH's latest standards. So the two leading guidelines partly vouch for each other instead of being checked independently.
Authors judging their own approach: Panel members Cohen-Kettenis and Gooren helped create the Dutch approach that the teen advice rests on. That approach's evidence, small Amsterdam studies with no comparison group, selective reporting of results and people lost to follow-up, has since been strongly criticised (for example Abbruzzese, Levine and Mason, Journal of Sex and Marital Therapy 2023).
Authors also provide the treatment: Several members led or worked in gender clinics that give the recommended treatments (for example in Amsterdam, UCSF, Boston University and Ghent). No independent panel balanced out this professional stake.
Consent claim not backed up: The claim that most teens can consent to partly permanent hormone treatment by 16, and that 'compelling reasons' may justify earlier treatment, is not supported by cited research on teens' decision-making or long-term results.
Outdated evidence: The guideline came before the rise in teen-onset cases, mostly in girls, who differ from the group the Dutch approach was based on. It also came before the evidence reviews by England's NICE (2020), Sweden (2022), Finland (2020) and the University of York (2024). Those found low or very low certainty of benefit and led those health systems to restrict medical transition for young people.
Advocacy message: The Society's launch press release called on policymakers to consider a biological basis for gender identity. That is a political position that goes beyond what its own graded evidence supports.

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Summary

Key findings

Abstract

Conclusion