Reading The Evidence – Let’s Get This Party Started (April 2025)

More than 2,000 scientific studies have examined aspects of gender-affirming care since 1975, including more than 260 studies cited in the Endocrine Society’s Clinical Practice Guideline. This blog is going to check out the making of the guideline and the article that announced the guideline task force’s recommendations for gender affirming care. This is the baseline evidence supporting providing gender care and how to do it. When you see or hear assertions that there is not evidence, or there isn’t any good evidence, this guideline, and the process for building the guideline is the pushback. Look closely at the differences between the science that each side cites.

The current full guideline was published in 2017 and two updates were issued in 2018. The citation for this guideline is:

The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 11, 1 November 2017, Pages 3869–3903, https://doi.org/10.1210/jc.2017-01658 (The full paper is available at that link. You can get a copy. It’s free!)

Published: 13 September 2017

The full article is 35 pages long, so we won’t be going through it page by page.

For this blog, we’ll cover the Abstract of the study, some information about how the task force gathered evidence, and their high-level conclusions about gender affirming care.

In our last blog, we discussed how to read an article. We’ll use some of those lessons here.

A great resource for more in-depth learning about evidence-based medicine is the Cochrane Reviews – they’re the best in the business and provide online lessons to learn more about what evidence-based medicine is and how to develop your skills. Free to register! https://training.cochrane.org/essentials

Let’s dive in to the Abstract.

For each part in the Abstract, more detail can be found later on in the body of the paper.

The Objective: To update the “Endocrine Treatment of Transsexual* Persons: An Endocrine Society Clinical Practice Guideline” (Within the article the authors note that the current system of the American Psychiatric Association was using “gender dysphoria” in 2017 and that, at the time of publishing, the ICD-11 has proposed using the term “gender incongruence”. Terminology changes!)

This is a good time to check out the references at the end of the paper: there are 265 separate papers that the task force identified, read, reviewed, and weighed for what the information in those articles said about gender affirming care and how we should practice it. If anyone tells you that there isn’t much science….well, here are at least 265 articles.

This guideline is now nearly 10 years old: there are even more studies now. Some newer studies have changed how we provide care, which is a good thing: science and healthcare EVOLVE. The overwhelming majority of studies support gender care.

Diving into this guideline can help us understand how standards of care are reached: they are not arbitrary!

Participants: Nine experts in the field (of developing medical guidelines) plus a methodologist and a medical writer. (There are 10 authors listed, all members of the task force. You can find their names on the first page of the article and Financial Disclosures are on page 27.)

Important information about the participants: All participants were required to reveal any potential conflicts of interest before joining the task force. This is an important step in judging whether a study has potential bias or not. When a study is cited, take a moment to check out the authors and ask some questions:

• Who are they?
• What is their training? What else have they written?
• Are they experts in the field they are writing about?
• Did they get PAID for this work? If they did, by WHOM?
• Do they have a known political bias or personal agenda?

• For this study, all participants were required to reveal any potential conflicts of interest before joining the task force.
  • Potential conflicts of interest (MONEY!) include:
  • getting paid in any amount from commercial interests
  • any grants, research support, consulting fees, salary, ownership interests such as stocks, honoraria and other payments for speaking on or participating in a panel or board, and any other financial goodies.

Evidence: the task force specifically paid for two “systematic reviews“ which are searches of literature databases for articles containing specific terms. These are two questions that the task force wanted a full picture of the available evidence to inform their recommendations: how do hormones affect heart disease and bone health?

• The first systematic review looked at the effect of testosterone and estradiol taken by transgender people on cholesterol and heart disease. This review found 29 “eligible studies at moderate risk of bias“.

• The second systematic review looked for studies about the effects of testosterone and estradiol on bone health in transgender people. The review found 13 studies.

Deep Dive Into What The Heck Did You Just Say

What is a systematic review? What is a moderate risk of bias?

An attempt to answer a common clinical question by finding all of the studies that address a specific question. The information in all of those studies is weighed and then summarized so that the systematic review creates a picture of what we know about the topic. It’s important to pay attention to the “systematic” part: you’re using a specific process to look for all of the evidence. A systematic review uses methodology to limit the chance that conclusions are skewed by bias. (From Cochrane)

What’s bias?

In non-clinical speak, bias is prejudice. In clinical terms, bias the the chance that the study results were affected by how the study was built or how the numbers were crunched, or how people were included or excluded in the study. In a systematic review, we want to know about

• selection bias (were there factors that affected which studies were selected for inclusion?)
• information bias (is there an error in how the information was measured or crunched?)
• reporting bias (are some conclusions highlighted over others? Is the data complete? Is the complete picture included in the conclusions?)
• confounding bias (factors that may affect both the intervention and the outcome. Confounders are lessened when the groups of patients in a study who get the intervention are matched very closely with the groups that do not get the intervention. Statistics can help identify where confounding bias may appear, too.

Among researchers and scientists there is an agreement on how to judge potential bias. There’s a tool! The tool will determine an overall risk of bias for each study: low, moderate, serious, or critical. You can check out a version of these tools at riskofbias.info. Here’s a quick description of each bias level (wording changed slightly):

Low: There is little or no concern about bias.

Moderate: There is some concern about bias, although it is not clear that there is an important risk of bias.

Serious: The study has some important problems. Characteristics of the study give rise to a serious risk of bias.

Critical: The study is very problematic. Characteristics of the study give rise to a critical risk of bias, such that and the result should generally be excluded from evidence syntheses.

Conclusions, Part One: Adolescents

Okay, WHAT? So DENSE!

Here are the highlights for the task force’s 2017 recommendations for YOUTH gender care:

• The assumed goals of gender affirming care in adolescents are to suppress the hormones that the body is already making and to keep the levels of the desired hormones at the expected levels found in the youth’s peers.
• The task force does not recommend hormone treatment for anyone who hasn’t reached puberty.
• The clinicians who treat trans youth should be trained in gender affirming care for adolescents.
• The task force does recommend blockers at Tanner Stage 2 (the start of puberty).
• Affirming hormones may be added when the youth persists – they still want them! – and when the youth shows that they have the ability to understand and consent to this treatment.
  • The task force gives an age when youth are “old enough”: by age 16, although some youth are better served by starting earlier.
• The best way to do gender care is when a multidisciplinary team of medical and mental health professionals can work together.

Conclusions Part 2 – Adults

Here are the Task Forces’ recommendations for ADULT gender care:

• The treating clinicians should be trained in gender care.
• The task force recommends that individuals should be monitored for known risks and complications and hormone levels should be maintained at levels appropriate for adult humans.
• If high levels of hormones are needed to suppress what the body makes by itself, consider surgery to remove the gonads (orchiectomy, generally). After surgery, it is likely that dosages can be lowered.
• Monitor existing reproductive body parts appropriately for cancer (pap smears, mammos, prostate checks).
• If surgery is desired, the surgeon should talk to the hormone provider to confirm surgery criteria.
• Avoid using hormones in people who will not benefit from the effects of hormones (this is where informed consent comes in!)

We won’t include the full list of references from this guideline review, but some of the ones that we typically cite when we’re writing letters to medical boards and legislators:

• Chen D, Berona J, Chan YM, Ehrensaft D, Garofalo R, Hidalgo MA, Rosenthal SM, Tishelman AC, Olson-Kennedy J. Psychosocial Functioning in Transgender Youth after 2 Years of Hormones. N Engl J Med. 2023 Jan 19;388(3):240-250. doi: 10.1056/NEJMoa2206297. PMID: 36652355.
• Tordoff DM, Wanta JW, Collin A, Stepney C, Inwards-Breland DJ, Ahrens K. Mental Health Outcomes in Transgender and Nonbinary Youths Receiving Gender-Affirming Care. JAMA Netw Open. 2022 Feb 1;5(2):e220978. doi: 10.1001/jamanetworkopen.2022.0978. Erratum in: JAMA Netw Open. 2022 Jul 1;5(7):e2229031. PMID: 35212746; PMCID: PMC8881768.
• Olson KR, Durwood L, Horton R, Gallagher NM, Devor A. Gender Identity 5 Years After Social Transition. Pediatrics. 2022 Aug 1;150(2):e2021056082. doi: 10.1542/peds.2021-056082. PMID: 35505568.
• Lieke J.J.J. Vrouenraets, Martine C. de Vries, Irma M. Hein, Marijn Arnoldussen, Sabine E. Hannema & Annelou L.C. de Vries (2022) Perceptions on the function of puberty suppression of transgender adolescents who continued or discontinued treatment, their parents, and clinicians, International Journal of Transgender Health, 23:4, 428-441, DOI: 10.1080/26895269.2021.1974324
• Clara De Castro, Mireia Solerdelcoll, Maria Teresa Plana, Irene Halperin, Mireia Mora, Laura Ribera, Camil Castelo-Branco, Esther Gómez-Gil, Angela Vidal, High persistence in Spanish transgender minors: 18 years of experience of the Gender Identity Unit of Catalonia,Revista de Psiquiatría  y Salud Mental, 2022,ISSN 1888-9891, https://doi.org/10.1016/j.rpsm.2022.02.001
• Tordoff, D. M., Wanta, J. W., Collin, A., Stephney, C., Inwards-Breland, D. J., Ahrens, K. (2022) Mental Health Outcomes in Transgender and Nonbinary Youths Receiving Gender-Affirming Care. JAMA Network Open, 5(2), e220978.
• Turban JL, King D, Carswell JM, Keuroghlian AS. Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation [published correction appears in Pediatrics. 2021 Apr;147(4):]. Pediatrics. 2020;145(2):e20191725. doi:10.1542/peds.2019-1725
• Green, A. E., DeChants, J. P., Price, M. N., & Davis, C. K. (2021). Association of gender-affirming hormone therapy with depression, thoughts of suicide, and attempted suicide among transgender and nonbinary youth. Journal of Adolescent Health.
• de Lara, D. L., Rodríguez, O. P., Flores, I. C., Masa, J. L. P., Campos-Muñoz, L., Hernández, M. C., & Amador, J. T. R. (2020). Psychosocial assessment in transgender adolescents. Anales de Pediatría (English Edition), 93(1), 41-48.
• Kaltiala, R., Heino, E., Työläjärvi, M., & Suomalainen, L. (2020). Adolescent development and psychosocial functioning after starting cross-sex hormones for gender dysphoria. Nordic Journal of Psychiatry, 74(3), 213-219.
• Achille, C., Taggart, T., Eaton, N. R., Osipoff, J., Tafuri, K., Lane, A., & Wilson, T. A. (2020). Longitudinal impact of gender-affirming endocrine intervention on the mental health and well-being of transgender youths: preliminary results. International Journal of Pediatric Endocrinology, 2020(1), 1-5.
• Hodax JK, Wagner J, Sackett-Taylor AC, Rafferty J, Forcier M. Medical Options for Care of Gender Diverse and Transgender Youth. J Pediatr Adolesc Gynecol. 2020 Feb;33(1):3-9. doi: 10.1016/j.jpag.2019.05.010. Epub 2019 May 30. PMID: 31154017.
• Kuper, L. , L. E., Stewart, S., Preston, S., Lau, M., & Lopez, X. (2020). Body dissatisfaction and mental health outcomes of youth on gender-affirming hormone therapy. Pediatrics, 145(4).
• Allen, L. R., Watson, L. B., Egan, A. M., & Moser, C. N. (2019). Well-being and suicidality among transgender youth after gender-affirming hormones. Clinical Practice in Pediatric Psychology, 7(3), 302.
• Kimberly LL, Folkers KM, Friesen P, Sultan D, Quinn GP, Bateman-House A, Parent B, Konnoth C, Janssen A, Shah LD, Bluebond-Langner R, Salas-Humara C. Ethical Issues in Gender-Affirming Care for Youth. Pediatrics. 2018 Dec;142(6):e20181537. doi: 10.1542/peds.2018-1537. Epub 2018 Nov 6. PMID: 30401789.
• Wiepjes CM, Nota NM, de Blok CJM, et al.  The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): trends in prevalence, treatment, and regrets. J Sex Med. 2018;15(4):582-590.
• Simone Mahfouda, Julia K Moore, Aris Siafarikas, Florian D Zepf, Ashleigh Lin, Puberty suppression in transgender children and adolescents, The Lancet Diabetes & Endocrinology, Volume 5, Issue 10, 2017, Pages 816-826, ISSN 2213-8587, https://doi.org/10.1016/S2213-8587(17)30099-2
• De Vries, A. L., McGuire, J. K., Steensma, T. D., Wagenaar, E. C., Doreleijers, T. A., & Cohen-Kettenis, P. T. (2014). Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics, 134(4), 696-704.
• de Vries AL, Steensma TD, Doreleijers TA, Cohen-Kettenis PT. Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med. 2011 Aug;8(8):2276-83. doi: 10.1111/j.1743-6109.2010.01943.x. Epub 2010 Jul 14. PMID: 20646177.

Stay in touch with us!