Study outcomes quoted for psychological benefit not holding up with time
Thank you to the BMJ for this excellent and thorough report on the state of evidence behind medical interventions for gender dysphoria, and the relation between evidence-based medicine approaches and the Endocrine Society, AAP and WPATH recommendations.
The Endocrine Society and WPATH recommendations both refer to and appear to rely upon positive psychological outcomes from the “Dutch Protocol,” a carefully vetted cohort of 70 young people on puberty blockers, 55 of whom were also later assessed at least a year past surgery  . However, , de Vries et al. (2011), recently failed replication. In addition, , de Vries et al. (2014), not only dropped the patient who died as a result of surgical complications (one of the 70 who was not reported in the final 55), but changed the test for gender dysphoria before and after surgery, confounding their main reported benefit of improvement in gender dysphoria [7,8]. Longer term outcomes are now becoming available for some of those treated with the Dutch protocol, with 60% of those in their early to mid-thirties still single, around 70% of the MTF reporting apparent sexual problems, and over half of the MTF having had shame for their “operated vagina.” Significant medical difficulties related to medical and surgical interventions are also becoming increasingly known[9,10,11,12].
More generally, interpreting outcomes for these treatments also tends to be difficult due to confounding by mental health interventions and the possible placebo effect.
Block’s  findings are complemented by 's systematic review and quality appraisal of the Endocrine Society recommendations, and the accompanying rapid response  discussing the 2022 WPATH recommendations. For the AAP 2018 recommendations also discussed by Block, a notable evidence related concern is that the authors “misrepresented the contents of its citations, which repeatedly said the very opposite of what AAP attributed to them”.
In addition to the lack of information about likely long term outcomes for medical interventions and their considerable physical risks, it is unclear how to determine when mental health interventions alone, such as exploratory therapy[18,19], will resolve gender dysphoria. Ideally this article will increase awareness of the low quality of the evidence base, and motivate better (sufficiently long and more complete) follow up, with outcomes reported in studies which use appropriate measurement instruments and inclusion criteria. The points of expert disagreement and significant lack of reliable evidence regarding risks, benefits and alternatives, as outlined in this article, should be reported to those considering such interventions in order for them to be able to provide true informed consent.
Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab2017;102:3869-903. doi:10.1210/jc.2017-01658 pmid:28945902. Erratum in: J Clin Endocrinol Metab. 2018 Feb 1;103(2):699. Erratum in: J Clin Endocrinol Metab. 2018 Jul 1;103(7):2758-2759. PMID: 28945902
 Rafferty J, Committee on Psychosocial Aspects of Child and Family Health, Committee on Adolescence, Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents. Pediatrics2018;142:e20182162. doi:10.1542/peds.2018-2162 pmid:30224363
Coleman E, Radix AE, Bouman WP, et al. Standards of care for the health of transgender and gender diverse people, version 8. Int J Transgend Health2022;23(Suppl 1):S1-259. doi:10.1080/26895269.2022.2100644 pmid:36238954
 De Vries AL, Steensma TD, Doreleijers TA, et al. Puberty suppression in adolescents with gender identity disorder: A prospective follow‐up study. The journal of sexual medicine. 2011 Aug;8(8):2276-83.
 De Vries AL, McGuire JK, Steensma TD, et al. Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics. 2014 Oct;134(4):696-704.
 Carmichael P, Butler G, Masic U, et al. Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK. PloS one. 2021 Feb 2;16(2):e0243894.
 Levine SB, Abbruzzese E, Mason JW. Reconsidering informed consent for trans-identified children, adolescents, and young adults. Journal of Sex & Marital Therapy. 2022 Oct 3;48(7):706-27.
 Abbruzzese E, Levine SB, Mason JW. The Myth of “Reliable Research” in Pediatric Gender Medicine: A critical evaluation of the Dutch Studies—and research that has followed. Journal of Sex & Marital Therapy. 2022 Dec 8:1-27.
 Nota NM, Wiepjes CM, de Blok CJ, et al. Occurrence of acute cardiovascular events in transgender individuals receiving hormone therapy: results from a large cohort study. Circulation. 2019 Mar 12;139(11):1461-2.
 Cheng PJ, Pastuszak AW, Myers JB, et al. Fertility concerns of the transgender patient. Translational Andrology and Urology. 2019 Jun;8(3):209.
 de Blok CJ, Wiepjes CM, van Velzen DM, et al. Mortality trends over five decades in adult transgender people receiving hormone treatment: a report from the Amsterdam cohort of gender dysphoria. The Lancet Diabetes & Endocrinology. 2021 Oct 1;9(10):663-70.
 Biggs M. Revisiting the effect of GnRH analogue treatment on bone mineral density in young adolescents with gender dysphoria. Journal of Pediatric Endocrinology and Metabolism. 2021 Jul 1;34(7):937-9.
 Clayton A. Gender-affirming treatment of gender dysphoria in youth: A perfect storm environment for the placebo effect—the Implications for research and clinical practice. Archives of Sexual Behavior. 2023 Feb;52(2):483-94.
 Block J. Gender dysphoria in young people is rising—and so is professional disagreement. bmj. 2023 Feb 23;380.
 Dahlen S, Connolly D, Arif I, et al. International clinical practice guidelines for gender minority/trans people: Systematic review and quality assessment. BMJ open. 2021 Apr 1;11(4):e048943.
 Dahlen S, Meads C, Bewley S. WPATH Standards of Care: A new edition using outdated methods weakens the trustworthiness of content. BMJ Rapid response. 2022 October 21
Retrieved Mar 7, 2023 from https://bmjopen.bmj.com/content/11/4/e048943.responses#wpath-standards-o....
 Cantor JM. Transgender and gender diverse children and adolescents: fact-checking of AAP policy. Journal of sex & marital therapy. 2020 May 18;46(4):307-13.
 Gender Exploratory Therapy Association, https://www.genderexploratory.com/
 Evans S, Evans M. Gender Dysphoria: A Therapeutic Model for Working with
Children, Adolescents and Young Adults. Bicester, England: Phoenix Publishing House 2021.
Competing interests: No competing interests