The Evidence for Gender-affirming Medical Interventions for Transgender Adolescents

Research suggests gender-affirming medical care results in better mental health. Here are the studies.

Key Points

• At least twenty studies to date have examined the impact of gender-affirming medical care on the mental health of transgender adolescents.

• Existing evidence suggests that gender-affirming medical care results in favorable mental health outcomes.

• All major medical organizations oppose legislation that would ban gender-affirming medical care for transgender adolescents.

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I'm a physician-scientist who studies the mental health of transgender and gender diverse youth. I’ve also historically spent a lot of time on Twitter. I've noticed there seem to be hundreds—if not thousands—of Twitter accounts that repeatedly post that there is no evidence supporting gender-affirming medical care for adolescent gender dysphoria. That is simply false.

Since several United States have passed legislation to outlaw gender-affirming medical care (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. The studies are in chronological order. I'll provide a brief summary of each, along with 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: deVries, 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.

Study 2: deVries, 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.

This study had a substantially long period of follow up: a mean 5.9 years after initiation of pubertal suppression.

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. It followed 101 adolescents who received pubertal suppression and 100 adolescents who were deemed by the team not ready to start pubertal suppression (likely due to mental health comorbidities). Both received psychotherapy for the first six months. During that six months, the patients with mental health comorbidities had mental health improve, whereas those without other mental health issues did not. This seems to suggest that psychotherapy helped with mental health problems other than gender dysphoria, but not gender dysphoria itself.

For the next 12 months, one group received pubertal suppression and the other received ongoing psychotherapy only. Over that time, the group that received pubertal suppression saw mental health improvements, while the group without pubertal suppression did not.

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 a statistically significant increase in general well-being and a statistically significant decrease in suicidality.

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.

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 had received pubertal suppression had better mental health outcomes than those who did not receive pubertal suppression.

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, those receiving gender-affirming medical interventions saw improvement in depression, suicidality, and quality of life. Of note, due to the small sample size, their regression analyses were likely underpowered. They did, however, nonetheless detect that treatment with pubertal suppression was associated with improved depression for transgender girls after adjusting for psychotherapy engagement and psychiatric medication usage.

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.

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 for which they ran statistical analyses (positive or negative). As the authors note in their discussion, this “may relate simply to [the small] sample size.” It also could be because they did not run analyses on some variables that showed statistically significant improvement in their past study (e.g., global functioning scores improved in the study, but statistical analyses were not reported on this variable).

Because mental health generally worsens as puberty progresses for those with adolescent gender dysphoria, a non-worsening of mental health in this uncontrolled study may represent a good outcome. 57% of patients in this study also received pubertal suppression in Tanner 4 or Tanner 5 of puberty (the latest two stages of puberty). Given that puberty is mostly complete by those stages, the medications were unlikely to have a significant physical effect on secondary sex characteristic development. When pubertal suppression is given late in puberty as monotherapy, it also increases the likelihood of menopause-like or andropause-like symptoms like hot flashes, which had led many clinicians to not consider them at these late stages of puberty. Despite this, the paper notes that “all young people affirmed at each interview that they wished to continue with GnRHa treatment” suggesting overall satisfaction with the treatment.

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 (e.g., 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. One important noted possibility is that adolescents are required, under current guidelines, to have interface with mental health providers as a prerequisite to accessing gender-affirming medical interventions.

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, 70(4), 643-649.

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).

Mental health outcomes for the adolescent-initiation group were examined six to seven years after gender-affirming hormones were started, a substantially long follow up period.

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.

Study 17: Chen, D., Berona, J., Chan, Y. M., Ehrensaft, D., Garofalo, R., Hidalgo, M. A., ... & Olson-Kennedy, J. (2023). Psychosocial functioning in transgender youth after 2 years of hormones. New England Journal of Medicine, 388(3), 240-250.

This study was an uncontrolled prospective cohort study from a four-site NIH-funded study. It followed 315 patients with adolescent gender dysphoria who received gender-affirming hormones (i.e., estrogen or testosterone) over two years. Over the course of the study, they found improvements in appearance congruence, positive affect, life satisfaction, depression, and anxiety symptoms. In parallel process models, they found that appearance congruence improvements tracked along with other mental health improvements, suggesting that the physical changes from the hormones were drivers of mental health improvement.

Study 18: Chelliah, P., Lau, M., & Kuper, L. E. (2024). Changes in gender dysphoria, interpersonal minority stress, and mental health among transgender youth after one year of hormone therapy. Journal of Adolescent Health, 74(6), 1106-1111.

This uncontrolled longitudinal cohort study from Dallas, Texas followed 115 adolescents with gender dysphoria for one year following gender-affirming medical treatment. Body dissatisfaction, victimization, depression, anxiety, and quality of life were improved after treatment.

Study 19: Olson-Kennedy, J., Wang, L., Wong, C. F., Chen, D., Ehrensaft, D., Hidalgo, M. A., ... & Rosenthal, S. M. (2025). Emotional Health of Transgender Youth 24 Months After Initiating Gender-Affirming Hormone Therapy. Journal of Adolescent Health. [In Press]

This publication reports on the same 315 adolescents as Chen et al. (Study 17). It examined a different set of outcomes (the NIH Toolbox Emotion Battery) in more detail and found improvements in social satisfaction, self-efficacy, social perception, and negative affect. They again found that appearance congruence tracked along with improvements in mental health, suggesting the improvements in mental health were from hormonal effects on secondary sex characteristics.

Study 20: Grant, R., Amos, N., Lin, A., Cook, T., Hill, A. O., Pang, K., ... & Bourne, A. (2024). Mental health and wellbeing outcomes associated with social, medical, and legal gender affirmation among trans young people in Australia. International Journal of Transgender Health, 1-13.

This study used cross-sectional data from an online survey of 1,697 Australian youth who were transgender, ages 14-21. Access to gender-affirming medical interventions was associated with lesser psychological distress (measured by the Kessler-12 scale) and anxiety (measured by the GAD-7). Statistically significant differences were not detected for measures of suicidality or non-suicidal self injury. Each of the regression models controlled for the potential confounding effects of demographic traits including age, gender, sexual orientation, level of education, and residential location. In addition, all regression analyses controlled for the potential confounding effects of past-12 month verbal harassment.

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. However, there has been one Australian randomized controlled trial of gender-affirming hormones in adults that found improvement in mental health with treatment.

Conclusion

In summary, there have been, to my knowledge, 20 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 studies I have not yet included.