The Evidence for Trans Youth Gender-Affirming Medical Care

NOTE: This post was updated on October 11, 2022. In discussions of studies 5, 7, 8 and 10, the final sentence was appended to include further information about the study.

I'm a physician-scientist who studies the mental health of transgender and gender diverse youth. I also spend a lot of time on Twitter. And yes I know, that's my first mistake. I've noticed there seem to be hundreds if not thousands of Twitter accounts that will repeatedly post that there is no evidence that gender-affirming medical care results in good mental health outcomes for transgender youth.

Since several U.S. states are introducing legislation to outlaw gender-affirming medical care this year (despite opposition from just about every major medical organization including The American Medical Association, The American Academy of Pediatrics, and The American Psychiatric Association), I thought this was a good time to review the relevant research for you all. So buckle up — here we go. The studies are in chronological order. I'll provide a brief summary of each and provide the citation for people who want to read more. I'll plan on updating this post as new studies become available. As you read, please keep in mind that all studies have methodological strengths and weaknesses and conclusions must be drawn from all of these studies together.

The Studies

Study 1: De Vries, A. L., Steensma, T. D., Doreleijers, T. A., & Cohen‐Kettenis, P. T. (2011). Puberty suppression in adolescents with gender identity disorder: A prospective follow‐up study. The Journal of Sexual Medicine, 8(8), 2276-2283.

This study from the Netherlands followed 70 transgender adolescents and measured their mental health before and after pubertal suppression. Study participants had improvements in depression and global functioning following treatment. However, feelings of anxiety and anger, gender dysphoria, and body satisfaction did not change.

Study 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.

Another study from the Netherlands. This one followed 55 transgender adolescents through pubertal suppression, gender-affirming hormone treatment (estrogen or testosterone), and gender-affirming genital surgery (as adults). Of note, many of these participants were also participants in study 1 (this study followed them for longer). The researchers found that psychological functioning steadily improved over the course of the study and by adulthood these now young adults had global functioning scores similar to or better than age-matched peers in the general population. Of note, one patient in this study died from a surgical complication of vaginoplasty (necrotizing fasciitis), but little additional information is provided.

Study 3: Costa, R., Dunsford, M., Skagerberg, E., Holt, V., Carmichael, P., & Colizzi, M. (2015). Psychological support, puberty suppression, and psychosocial functioning in adolescents with gender dysphoria. The Journal of Sexual Medicine, 12(11), 2206-2214.

This study is from the United Kingdom. They followed 101 adolescents who received pubertal suppression at the beginning of the study and 100 adolescents who, for a range of reasons, were deemed by the team not ready to start pubertal suppression and thus did not receive it over the course of the study. Both groups received supportive psychotherapy. Both groups saw improvement in mental health. While the pubertal suppression group had a 5-point higher mean score on the study's psychological functioning scale at the end of the study, the difference was not statistically significant. This could have been due to the small sample size by the end of the study (the researchers only had data from 36 participants in the therapy-only group and 35 participants in the pubertal suppression group at the final time point of the study). We will see that later studies were able to obtain larger sample sizes so that statistically significant differences between those who did and did not receive pubertal suppression could be detected.

Study 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.

This study was from researchers at Children's Mercy Hospital Gender Pathway Services Clinic in Missouri. They followed 47 transgender adolescents who received gender-affirming hormones (estrogen or testosterone) to a mean 349 days after starting treatment. They found statistically significant increases in general well-being and a statistically significant decrease in suicidality. Of note, the adolescents also received psychotherapy.

Study 5: 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.

This study is from Finland. Researchers conducted a retrospective chart review of 52 adolescents who received gender-affirming hormones (estrogen or testosterone) and found statistically significant decreases in need for specialist level psychiatric treatment for depression (decreased from 54% to 15%), anxiety (decreased from 48% to 15%), and suicidality or self-harm (decreased from 35% to 4%) following treatment. However, the authors note that gender reassignment is "not enough to improve functioning and relieve psychiatric comorbidities among adolescents with gender dysphoria."

Study 6: 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.

This study is from Spain. It followed 23 transgender adolescents who received gender-affirming hormones (estrogen or testosterone) and 30 cisgender controls for approximately one year. They found the transgender adolescents at baseline had worse measures of mental health than the cisgender control adolescents but that this difference equalized by the end of the study. The transgender adolescents in the study who received gender-affirming hormones had statistically significant improvements in several mental health measures, including anxiety and depression.

Study 7: van der Miesen, A. I., Steensma, T. D., de Vries, A. L., Bos, H., & Popma, A. (2020). Psychological functioning in transgender adolescents before and after gender-affirmative care compared with cisgender general population peers. Journal of Adolescent Health, 66(6), 699-704.

This was another Dutch study, with an impressive sample size. Researchers compared 272 transgender adolescents referred to the gender clinic who had not yet received pubertal suppression with 178 transgender adolescents who had received pubertal suppression. They found those who received pubertal suppression had better mental health outcomes than those who did not receive pubertal suppression. However, because subjects received psychotherapy, the authors note that the study does not provide "direct evidence" that pubertal suppression improves mental health in transgender youth.

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Study 8: 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.

This study was from Stony Brook Children's Hospital in New York. It followed 50 transgender adolescents longitudinally. Over the course of the study, 23 received pubertal suppression only, 35 received gender-affirming hormones only, and 11 received both. Three participants received no gender-affirming medical interventions. Over the course of the study, there was a statistically significant decrease in depression scores in one group: Male-to-female transitioners who underwent puberty suppression only.

Study 9: Kuper, 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).

This study was from a gender clinic in Dallas, Texas. The researchers followed 148 transgender adolescents who were receiving gender-affirming medical treatment. 25 received pubertal suppression only, 93 received gender-affirming hormones (estrogen or testosterone) only, and 30 received both. 15 participants received gender-affirming chest surgery. When examining all participants together, the study found statistically significant improvements in body dissatisfaction, depressive symptoms, and anxiety symptoms.

Study 10: Turban, J. L., King, D., Carswell, J. M., & Keuroghlian, A. S. (2020). Pubertal suppression for transgender youth and risk of suicidal ideation. Pediatrics, 145(2).

This study was conducted by myself along with several other researchers from Harvard Medical School. It utilized data from a non-probability sample of 20,619 transgender adults who reported ever wanting pubertal suppression. Of these, 89 actually received pubertal suppression. After adjusting for potentially confounding variables, access to pubertal suppression was associated with a lower odds of lifetime suicidal ideation. Of note, this study did not identify psychotherapy as a potentially confounding variable.

Study 11: Carmichael, P., Butler, G., Masic, U., Cole, T. J., De Stavola, B. L., Davidson, S., ... & Viner, R. M. (2021). 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, 16(2), e0243894.

This is another study from the United Kingdom. Researchers presented data for transgender adolescents who had received pubertal suppression. They had data for 44 patients after 12 months of treatment, 24 patients after 24 months of treatment, and 14 patients after 36 months of treatment. They were unable to detect any changes on their mental health measures (positive or negative).

Study 12: Grannis, C., Leibowitz, S. F., Gahn, S., Nahata, L., Morningstar, M., Mattson, W. I., ... & Nelson, E. E. (2021). Testosterone treatment, internalizing symptoms, and body image dissatisfaction in transgender boys. Psychoneuroendocrinology, 132, 105358.

This study recruited 42 birth-assigned female adolescents from a gender clinic in Ohio. Nineteen were receiving testosterone and 23 were not. Those not receiving testosterone were not receiving it due to a number of reasons (referred to endocrinology but hadn't started, parents not providing consent, and one was not interested in testosterone). The adolescents who were receiving testosterone treatment had lower scores on measures of generalized anxiety, social anxiety, depression, and body image dissatisfaction.

Study 13: Hisle-Gorman, E., Schvey, N. A., Adirim, T. A., Rayne, A. K., Susi, A., Roberts, T. A., & Klein, D. A. (2021). Mental healthcare utilization of transgender youth before and after affirming treatment. The Journal of Sexual Medicine, 18(8), 1444-1454.

This study utilized military healthcare data from transgender youth who received medical care through the U.S. military healthcare system. The researchers identified 963 transgender adolescents who had received some form of gender-affirming medical treatment. The mean age of starting any gender-affirming medical care was 18.2 (so this study may not technically qualify for our review of studies of adolescents). Their outcomes of interest were number of mental healthcare visits after gender-affirming medical care and number of days taking a psychiatric medication after starting gender-affirming medical care. In their adjusted models, there was no change in number of annual mental healthcare visits and an increase in days taking psychiatric medication from a mean 120 days per year to a mean 212 days per year. It's difficult to make firm conclusions based on this study, given the unusual outcome measure of number of days per year taking a psychiatric medication. The authors present a range of possible interpretations in the discussion section of the manuscript for those who are interested.

Study 14: 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.

This study was conducted by researchers from The Trevor Project. They recruited 5,753 transgender adolescents who said they wanted gender-affirming hormone treatment (estrogen or testosterone). Of these, 1,216 had accessed gender-affirming hormones treatment. To focus on the results for only participants who were under 18: After adjusting for potential confounding variables, access to gender-affirming hormones was associated with lower odds of recent depression and suicide attempts when compared to those who desired but did not access gender-affirming hormones.

Study 15: Turban, J. L., King, D., Kobe, J., Reisner, S. L., & Keuroghlian, A. S. (2022). Access to gender-affirming hormones during adolescence and mental health outcomes among transgender adults. PLoS One, 17(1), e0261039.

This study was also conducted by me and other researchers at Harvard Medical School. We examined 21,598 adults who reported ever desiring gender-affirming hormones (estrogen or testosterone). Of these, 481 accessed gender-affirming hormones during adolescence, 12,257 accessed gender-affirming hormones as adults, and 8,860 were never able to access gender-affirming hormones. We found that regardless of age of initiation, accessing gender-affirming hormones was associated with lower odds of past-year suicidal ideation and past year severe psychological distress. We also found that access to gender-affirming hormones during adolescence was associated with a lower odds of these same adverse mental health outcomes when compared to not accessing gender-affirming hormones until adulthood. Because the study was cross-sectional, we created a variable for people who had suicidal ideation in the past but did not have it in the past year (a proxy for mental health improving over time). We found that people who accessed gender-affirming hormones were more likely to meet this criterion than people who desired but did not access gender-affirming hormones, arguing against reverse causation (a common problem with cross-sectional studies).

Study 16: 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.

This study was a prospective cohort study from Seattle Children's Gender Clinic. The researchers followed 104 transgender and non-binary youth who were receiving gender-affirming medical treatment. After adjusting for temporal trends and potential confounders, they found lower odds of depression and suicidality among young people who had started gender-affirming medical care, when compared to those who did not.

No Randomized Controlled Trials

One will notice that there have not been any randomized controlled trials. There is a general consensus in the field that such a trial would be unethical given the body of literature we have so far indicating that those in the control group would be likely to suffer adverse mental health outcomes compared to those randomized to the treatment groups. For this reason, it appears that no institutional review board would approve a randomized controlled trial at this time, under the principle of "equipoise" to which some bioethicists refer.

Conclusion

In summary, there have been, to my knowledge, 16 studies to date studying the impact of gender-affirming medical care for transgender adolescents. Taken together, the body of research indicates that these interventions result in favorable mental health outcomes. I will continue to update this post as new studies become available. Please feel free to contact me if you are aware of any new studies I have not yet included.