Last updated September 2026

A substantial and growing body of scientific literature has examined the health of transgender and gender-diverse adolescents, including gender affirming hormone therapy, puberty suppression, social affirmation, mental health, identity development, fertility, bone health, and the effects of discrimination and restrictions on care.

No individual study answers every clinical question. As with most areas of adolescent medicine, the evidence includes prospective cohort studies, retrospective cohorts, cross-sectional studies, qualitative research, systematic reviews, and clinical guidance. Taken together, the literature provides evidence relevant to the benefits, risks, limitations, and clinical use of gender affirming care.

Gender Affirming Hormones: Mental Health and Psychosocial Outcomes

• Chen D, Berona J, Chan YM, et al. Psychosocial Functioning in Transgender Youth after 2 Years of Hormones. N Engl J Med. 2023;388(3):240-250. doi:10.1056/NEJMoa2206297.
  • A prospective four-site U.S. study followed transgender and nonbinary youth for two years after beginning gender affirming hormones. Appearance congruence, positive affect, and life satisfaction increased, while depression and anxiety symptoms decreased. Improvements in appearance congruence were associated with better psychosocial outcomes. (DOI)
• Olson-Kennedy J, Wang L, Wong CF, et al. Emotional Health of Transgender Youth 24 Months After Initiating Gender-Affirming Hormone Therapy. J Adolesc Health. 2025;77(1):41-50. doi:10.1016/j.jadohealth.2024.11.014.
  • Using the prospective multicenter Trans Youth Care–United States cohort, investigators followed youth over 24 months of gender affirming hormone treatment. Emotional health improved over time, with improvements associated in part with increasing appearance congruence. This expands the earlier two-year prospective findings by examining a broader set of emotional-health measures. (PubMed)
• 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;5(2):e220978. doi:10.1001/jamanetworkopen.2022.0978.
  • In this prospective cohort of 104 transgender and nonbinary youth ages 13–20, receipt of puberty blockers or gender affirming hormones was associated over 12 months with 60% lower odds of moderate or severe depression and 73% lower odds of suicidality. (PubMed Central (PMC))
• Allen LR, Dodd CG, Moser CN, Knoll MM. Changes in Suicidality among Transgender Adolescents Following Hormone Therapy: An Extended Study. J Pediatr. 2026;289:114883. doi:10.1016/j.jpeds.2025.114883.
  • This retrospective longitudinal study included 432 transgender and gender-diverse adolescents and young adults with an average follow-up of approximately 22 months. Suicidality decreased significantly after hormone initiation, with the association observed across sex assigned at birth, age at treatment initiation, and treatment duration. (PubMed)
• Green AE, DeChants JP, Price MN, Davis CK. Association of Gender-Affirming Hormone Therapy With Depression, Thoughts of Suicide, and Attempted Suicide Among Transgender and Nonbinary Youth. J Adolesc Health. 2022;70(4):643-649. doi:10.1016/j.jadohealth.2021.10.036.
  • In a large U.S. survey containing nearly 12,000 transgender and nonbinary youth, access to gender affirming hormones was associated with lower odds of depression and suicidality among youth who wanted hormone treatment. (ScienceDirect)
• Turban JL, King D, Kobe J, Reisner SL, Keuroghlian AS. Access to gender affirming hormones during adolescence and mental health outcomes among transgender adults. PLoS One. 2022;17:e0261039. doi:10.1371/journal.pone.0261039.
  • Using the 2015 U.S. Transgender Survey, investigators compared adults who had wanted gender affirming hormones and accessed them during adolescence or adulthood with those who had wanted hormones but never received them. Hormone access during adolescence was associated with substantially lower odds of past-year suicidal ideation in adulthood. (PubMed Central (PMC))
• Chelliah P, Lau M, Kuper LE. Changes in Gender Dysphoria, Interpersonal Minority Stress, and Mental Health Among Transgender Youth After One Year of Hormone Therapy. J Adolesc Health. 2024;74(6):1106-1111. doi:10.1016/j.jadohealth.2023.12.024.
  • Among 115 transgender youth ages 12–18 followed during the first year of medical treatment, investigators observed reductions in body dissatisfaction, victimization, depression, and anxiety and improvements in psychosocial functioning and parental affirmation. (ScienceDirect)
• Nunes-Moreno M, Furniss A, Cortez S, et al. Mental Health Diagnoses and Suicidality Among Transgender Youth in Hospital Settings. LGBT Health. 2024.
  • Transgender and gender-diverse youth had substantially higher baseline rates of mental-health diagnoses and suicidality in emergency and inpatient settings. Among transgender youth prescribed gender affirming hormones, hormone treatment was associated with a 43.6% lower subsequent risk of documented suicidality. (PubMed)
• Kuper LE, Stewart S, Preston S, Lau M, Lopez X. Body Dissatisfaction and Mental Health Outcomes of Youth on Gender-Affirming Hormone Therapy. Pediatrics. 2020;145(4).
  • Longitudinal research examining youth receiving gender affirming hormones found that changes in body dissatisfaction were closely related to changes in depression and anxiety, supporting the importance of reducing distress related to incongruent physical characteristics.
• Grannis C, Leibowitz SF, Gahn S, et al. Testosterone Treatment, Internalizing Symptoms, and Body Image Dissatisfaction in Transgender Boys. Psychoneuroendocrinology. 2021;132:105358.
  • Transmasculine adolescents receiving testosterone had lower internalizing symptoms and greater body-image satisfaction than untreated participants; the study also investigated neurobiological correlates associated with treatment. (ScienceDirect)
• Allen LR, Watson LB, Egan AM, Moser CN. Well-Being and Suicidality Among Transgender Youth After Gender-Affirming Hormones. Clin Pract Pediatr Psychol. 2019;7(3):302-311.
  • A longitudinal study of 47 adolescents found improvement in psychological well-being and reductions in suicidality after initiation of gender affirming hormones. (Sage Journals)
• Achille C, Taggart T, Eaton NR, et al. Longitudinal Impact of Gender-Affirming Endocrine Intervention on the Mental Health and Well-Being of Transgender Youths: Preliminary Results. Int J Pediatr Endocrinol. 2020;2020.
  • This longitudinal study followed youth receiving puberty suppression or gender affirming hormones and reported improvements in psychological functioning over the course of endocrine treatment.
• Kaltiala R, Heino E, Työläjärvi M, Suomalainen L. Adolescent Development and Psychosocial Functioning After Starting Cross-Sex Hormones for Gender Dysphoria. Nord J Psychiatry. 2020;74(3):213-219.
  • This Finnish cohort followed adolescents receiving hormone therapy. Overall functioning improved during treatment, although significant psychiatric comorbidity remained in some patients, underscoring that gender affirming treatment does not substitute for appropriate mental-health care when it is needed.
• de Lara DL, Rodríguez OP, Flores IC, et al. Psychosocial Assessment in Transgender Adolescents. An Pediatr. 2020;93(1):41-48.
  • This study examined psychosocial characteristics of adolescents presenting for gender care and contributes to evidence documenting the psychological burden experienced by transgender youth and the need for comprehensive, affirming clinical support.

Puberty Suppression

• de Vries ALC, Steensma TD, Doreleijers TAH, Cohen-Kettenis PT. Puberty Suppression in Adolescents With Gender Identity Disorder: A Prospective Follow-Up Study. J Sex Med. 2011;8(8):2276-2283. doi:10.1111/j.1743-6109.2010.01943.x.
  • One of the foundational prospective studies of puberty suppression. Psychological and behavioral functioning was assessed before treatment and during GnRH-agonist therapy. Puberty-related distress improved while overall psychological functioning remained stable or improved, and participants were able to continue adolescent development without progression of unwanted secondary sex characteristics. (ScienceDirect)
• Costa R, Dunsford M, Skagerberg E, Holt V, Carmichael P, Colizzi M. Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria. J Sex Med. 2015;12(11):2206-2214. doi:10.1111/jsm.13034.
  • In a longitudinal cohort of 201 adolescents, psychological support alone was associated with improved global functioning. Adolescents who subsequently received puberty suppression demonstrated additional improvement in psychosocial functioning. (ScienceDirect)
• van der Miesen AIR, Steensma TD, de Vries ALC, Bos H, Popma A. Psychological Functioning in Transgender Adolescents Before and After Gender-Affirmative Care Compared With Cisgender General Population Peers. J Adolesc Health. 2020;66(6):699-704. doi:10.1016/j.jadohealth.2019.12.018.
  • Adolescents presenting before treatment had substantially more internalizing problems, suicidality/self-harm, and peer difficulties than cisgender peers. Adolescents receiving care that included puberty suppression had fewer psychological problems and functioning similar to or better than cisgender adolescents on several measures. (PubMed)
• Turban JL, King D, Carswell JM, Keuroghlian AS. Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation. Pediatrics. 2020;145(2):e20191725. doi:10.1542/peds.2019-1725.
  • Among transgender adults who had wanted puberty suppression during adolescence, those who reported having received it had lower odds of lifetime suicidal ideation than those who wanted but did not receive it. The study is retrospective and relies on adult recall, but provides evidence regarding longer-term associations.
• Vrouenraets LJJJ, de Vries MC, Hein IM, Arnoldussen M, Hannema SE, de Vries ALC. Perceptions on the Function of Puberty Suppression of Transgender Adolescents Who Continued or Discontinued Treatment, Their Parents, and Clinicians. Int J Transgend Health. 2022;23(4):428-441. doi:10.1080/26895269.2021.1974324.
  • This qualitative study deliberately included both adolescents who continued gender affirming treatment and adolescents who stopped puberty suppression. Participants described several functions of suppression: preventing unwanted pubertal development, providing time to explore gender, allowing families time to adjust, and, for many youth, functioning as the first step in medical transition. (Taylor & Francis Online)
• 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;16(2):e0243894.
  • The UK cohort found effective pubertal suppression and no major change across many psychological measures during treatment. Bone-density z-scores declined during suppression, an important physical-health consideration and reason for ongoing bone-health monitoring.
• Mahfouda S, Moore JK, Siafarikas A, Zepf FD, Lin A. Puberty Suppression in Transgender Children and Adolescents. Lancet Diabetes Endocrinol. 2017;5(10):816-826.
  • A clinical review of puberty suppression describing its rationale, available evidence, physical effects, psychosocial considerations, and areas requiring additional long-term research.
• Tornese GT, Di Mase R, Munarin J, et al. Use of Gonadotropin-Releasing Hormone Agonists in Transgender and Gender Diverse Youth: A Systematic Review. Front Endocrinol. 2025;16:1555186. doi:10.3389/fendo.2025.1555186.
  • New since the previous QueerDoc update. This systematic review evaluated 51 studies of GnRH agonists in transgender and gender-diverse youth. The literature consistently demonstrates effective pubertal suppression. The review describes favorable psychological findings in a number of studies while also emphasizing remaining uncertainty regarding long-term skeletal, fertility, sexual-function, and other outcomes.

Longer-Term Outcomes After Adolescent Gender-Affirming Treatment

• de Vries ALC, McGuire JK, Steensma TD, Wagenaar ECF, Doreleijers TAH, Cohen-Kettenis PT. Young Adult Psychological Outcome After Puberty Suppression and Gender Reassignment. Pediatrics. 2014;134(4):696-704. doi:10.1542/peds.2013-2958.
  • Fifty-five young adults were evaluated before puberty suppression, when hormones were initiated, and again in young adulthood after gender affirming treatment. Gender dysphoria decreased and psychological functioning steadily improved. By young adulthood, measures of well-being were similar to or better than those of same-age young adults in the general population. (PubMed)
• Hisle-Gorman E, Schvey NA, Adirim TA, et al. Mental Healthcare Utilization of Transgender Youth Before and After Affirming Treatment. J Sex Med. 2021;18(8):1444-1454. doi:10.1016/j.jsxm.2021.05.014.
  • Using U.S. military health-system data, investigators documented substantially greater baseline mental-health needs among transgender youth than among their cisgender siblings. Mental-health service use did not disappear after medical treatment, demonstrating the importance of continuing access to comprehensive behavioral-health care rather than treating hormones as a stand-alone mental-health intervention. (ScienceDirect)
• Ruuska SM, Tuisku K, Holttinen T, Kaltiala R. All-Cause and Suicide Mortalities Among Adolescents and Young Adults Who Contacted Specialised Gender Identity Services in Finland in 1996–2019: A Register Study. BMJ Ment Health. 2024;27.
  • This Finnish register study examined mortality among young people referred to specialist gender services. Suicide deaths were uncommon in absolute numbers, while psychiatric morbidity was an important correlate of mortality. It supports careful mental-health assessment and treatment alongside gender care.

Gender Identity Persistence, Treatment Continuation, and Detransition

• Olson KR, Durwood L, Horton R, Gallagher NM, Devor A. Gender Identity 5 Years After Social Transition. Pediatrics. 2022;150(2):e2021056082. doi:10.1542/peds.2021-056082.
  • Among 317 children who had socially transitioned, 94% were still living as binary transgender youth approximately five years later, 3.5% identified as nonbinary, and 2.5% identified as cisgender. Retransitions occurred but were uncommon, and some children retransitioned more than once. (PubMed Central (PMC))
• De Castro C, Solerdelcoll M, Plana MT, et al. High Persistence in Spanish Transgender Minors: 18 Years of Experience of the Gender Identity Unit of Catalonia. Span J Psychiatry Ment Health. 2024;17(1):35-40. doi:10.1016/j.rpsm.2022.02.001.
  • In this Catalonian clinical cohort, 97.6% of transgender minors continued to identify as transgender over a median 2.6 years of follow-up. (ScienceDirect)
• Boskey ER, Scheffey KL, Pilcher S, et al. A Retrospective Cohort Study of Transgender Adolescents’ Gender-Affirming Hormone Discontinuation. J Adolesc Health. 2025;76(4):584-591. doi:10.1016/j.jadohealth.2024.11.002.
  • Among 1,050 adolescents who had used gender affirming hormones for at least six months, 93% remained continuously on treatment at last contact and another group temporarily stopped and later restarted. Only five patients—approximately 0.5% of the cohort—stopped because they subsequently identified with the gender associated with their sex assigned at birth. Importantly, the study demonstrates why treatment discontinuation should not automatically be interpreted as regret or detransition. (PubMed)
• Metzger DL, Mokashi A, Pacaud D, et al. Stability of Transgender Identity in Adolescents Seen in Multidisciplinary Specialized Gender Centers: A Multicenter Study in Canada. J Adolesc Health. 2026;79(2):242-249. doi:10.1016/j.jadohealth.2026.03.016.
  • New in 2026. This multicenter Canadian study followed 445 adolescents referred to specialized gender clinics. The large majority continued to identify with a gender different from that typically associated with sex assigned at birth. Among those who began gender affirming hormones, discontinuation was uncommon. (PubMed)
• Wagner S, Panagiotakopoulos L, Nash R, et al. Progression of Gender Dysphoria in Children and Adolescents: A Longitudinal Study. Pediatrics. 2021;148.
  • A longitudinal clinical study examining the development of gender dysphoria over time, adding evidence that adolescent gender trajectories can be prospectively observed rather than inferred from older childhood clinic samples.
• 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.
  • This large Dutch clinical cohort—primarily adults—found regret following gender affirming medical treatment to be uncommon. It is useful contextual evidence about treatment persistence and regret, although it should not be represented as an adolescent-specific outcome study.
• Narayan SK, Hontscharuk R, Danker S, et al. Guiding the Conversation—Types of Regret After Gender-Affirming Surgery and Their Associated Etiologies. Ann Transl Med. 2021;9:605.
  • This review emphasizes that “regret” is not a single phenomenon: surgical complications, social circumstances, unsatisfactory aesthetic outcomes, shifts in identity, and other experiences can have different causes and should not be conflated. This is primarily adult surgical literature rather than evidence specific to adolescent medical treatment.

Bone Health and Physical Effects

• Tienforti D, Marinelli L, Terrana G, et al. Bone Accrual During Puberty Suppression and Gender-Affirming Therapy in Transgender Adolescents: A Systematic Review and Meta-Analysis. JAMA Pediatr. Published online August 3, 2026. doi:10.1001/jamapediatrics.2026.2470.
  • Important new 2026 evidence. This meta-analysis included 10 longitudinal cohorts totaling 751 adolescents. Bone-density z-scores decreased during GnRH-agonist suppression. Following initiation of gender affirming hormones, absolute bone mineral density increased and z-scores partially recovered. Values remained numerically below baseline at some sites, although differences were not consistently statistically significant. The authors characterize a persistent skeletal deficit as uncertain rather than demonstrated and emphasize attention to treatment duration and timely sex-steroid exposure. (PubMed)
• Ciancia S, Dubois V, Craen M, et al. Effects of Puberty Suppression on Bone, Body Composition, Handgrip Strength and Glucolipid Profile in Early-Pubertal Transgender Adolescents. Int J Transgend Health. 2025;26(3):861-873. doi:10.1080/26895269.2024.2353224.
  • This study followed adolescents receiving puberty suppression beginning in Tanner stage 2–3. Bone-density z-scores decreased during prolonged suppression, particularly at the lumbar spine; body composition shifted toward increased fat mass and decreased lean-mass acquisition. Insulin sensitivity and lipid profiles did not significantly worsen. These data support monitoring bone health during prolonged suppression rather than suggesting that puberty blockers have no physiologic effects. (PubMed)
• Bertelloni S, Baroncelli GI, Ferdeghini M, et al. Final Height, Gonadal Function and Bone Mineral Density of Adolescent Males With Central Precocious Puberty After Therapy With Gonadotropin-Releasing Hormone Analogues. Eur J Pediatr. 2000;159:369-374.
  • This study is not transgender-specific. It is part of the broader pediatric evidence demonstrating decades of clinical experience with reversible GnRH-agonist suppression and contributes background information about recovery of the hypothalamic-pituitary-gonadal axis and bone health after treatment.

Fertility and Reproductive Health

• Chen D, Simons L, Johnson EK, et al. Fertility Preservation for Transgender Adolescents. J Adolesc Health. 2017;61:120-123.
  • Discusses fertility-preservation decision-making for transgender adolescents and the importance of counseling prior to treatments that may affect reproductive potential.
• Lai TC, McDougall R, Feldman D, et al. Fertility Counseling for Transgender Adolescents: A Review. J Adolesc Health. 2020;66:658-665.
  • Reviews ethical and clinical considerations in adolescent fertility counseling, including developmental capacity, future reproductive goals, family involvement, dysphoria related to fertility procedures, and barriers to preservation.
• Neblett MF, Hipp HS. Fertility Considerations in Transgender Persons. Endocrinol Metab Clin North Am. 2019;48:391-402.
  • Reviews fertility effects and fertility-preservation options associated with gender affirming hormone therapy and surgery. It is useful clinical background but is not itself an adolescent treatment-outcome study.

Social Affirmation, Family Support, and Psychosocial Environment

• Grant R, Amos N, Lin A, et al. Mental Health and Wellbeing Outcomes Associated With Social, Medical, and Legal Gender Affirmation Among Trans Young People in Australia. Int J Transgend Health. 2024.
  • In a national sample of 1,697 transgender young people ages 14–21, social, legal, and medical affirmation were associated with better measures of mental health and well-being. Medical affirmation was associated with lower anxiety and psychological distress. (PubMed Central (PMC))
• Olson KR, Blotner C, Alonso D, et al. Family Discussions of Early Childhood Social Transitions. Clin Pract Pediatr Psychol. 2019;7:229-240.
  • Examines how transgender children and their families describe and navigate social transition, providing evidence about family processes and the diversity of pathways leading to social affirmation.
• Selkie E, Adkins V, Masters E, et al. Transgender Adolescents’ Uses of Social Media for Social Support. J Adolesc Health. 2020;66:275-280.
  • Transgender adolescents described online communities as important sources of identity exploration, health information, peer connection, and social support, while also describing potential risks associated with social media use.
• Adkins V, Masters E, Shumer D, Selkie E. Exploring Transgender Adolescents’ Use of Social Media for Support and Health Information Seeking. J Adolesc Health. 2018;62:S44.
  • Earlier research documenting the role online communities can play in support and health-information seeking among transgender adolescents.

Baseline Mental-Health Disparities and Other Health Needs

These studies do not demonstrate the effectiveness of gender affirming medical treatment themselves. They document health disparities and clinical needs that are important context for adolescent transgender medicine.

• Connolly MD, Zervos MJ, Barone CJ II, et al. The Mental Health of Transgender Youth: Advances in Understanding. J Adolesc Health. 2016;59:489-495.
  • A review documenting elevated rates of depression, anxiety, self-harm, and suicidality among transgender youth and discussing social and clinical factors associated with these disparities.
• Johns MM, Lowry R, Andrzejewski J, et al. Transgender Identity and Experiences of Violence Victimization, Substance Use, Suicide Risk, and Sexual Risk Behaviors Among High School Students—19 States and Large Urban School Districts, 2017. MMWR. 2019;68:67-71.
  • Large U.S. surveillance data showing marked disparities in violence exposure, suicidality, substance use, and other health risks among transgender high-school students compared with cisgender peers.
• Duffy ME, Henkel KE, Joiner TE. Prevalence of Self-Injurious Thoughts and Behaviors in Transgender Individuals With Eating Disorders: A National Study. J Adolesc Health. 2019;64:461-466.
  • Documents high rates of self-injurious thoughts and behaviors among transgender people with eating disorders, highlighting the intersection of gender minority stress, eating disorders, and suicide risk.
• Guss CE, Williams DN, Reisner SL, et al. Disordered Weight Management Behaviors, Nonprescription Steroid Use, and Weight Perception in Transgender Youth. J Adolesc Health. 2017;60:17-22.
  • Identifies elevated disordered weight-management behaviors and distinctive body-image concerns among transgender youth.
• Coelho JS, Suen J, Clark BA, et al. Eating Disorder Diagnoses and Symptom Presentation in Transgender Youth: A Scoping Review. Curr Psychiatry Rep. 2019;21:107.
  • Reviews emerging evidence regarding eating-disorder prevalence, presentations, screening, and treatment considerations in transgender young people.
• Avila JT, Golden NH, Aye T. Eating Disorder Screening in Transgender Youth. J Adolesc Health. 2019;65:815-817.
  • Discusses the need for appropriate eating-disorder screening in transgender adolescents and the relationship between gender dysphoria, body image, and disordered eating.

Access to Competent and Affirming Health Care

• Clark BA, Veale JF, Greyson D, et al. Primary Care Access and Foregone Care: A Survey of Transgender Adolescents and Young Adults. Fam Pract. 2018;35:302-306.
  • Documents barriers to primary care and instances in which transgender adolescents and young adults delayed or avoided needed medical care.
• Guss CE, Woolverton GA, Borus J, et al. Transgender Adolescents’ Experiences in Primary Care: A Qualitative Study. J Adolesc Health. 2019;65:344-349.
  • Transgender adolescents identified clinician knowledge, use of names and pronouns, confidentiality, clinic environment, and respectful communication as important determinants of whether primary-care encounters felt safe and useful.
• 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;33(1):3-9. doi:10.1016/j.jpag.2019.05.010.
  • Clinical review describing puberty suppression, gender affirming hormones, menstrual management, contraception, fertility considerations, and reproductive-health needs of transgender adolescents. (ScienceDirect)

Effects of Restricting Gender-Affirming Care and Anti-Transgender Policies

• Lee WY, Hobbs JN, Hobaica S, DeChants JP, Price MN, Nath R. State-Level Anti-Transgender Laws Increase Past-Year Suicide Attempts Among Transgender and Non-Binary Young People in the USA. Nat Hum Behav. 2024;8:2096-2106. doi:10.1038/s41562-024-01979-5.
  • Using a difference-in-differences design and data from more than 60,000 transgender and nonbinary young people, researchers examined suicide attempts before and after enactment of state anti-transgender laws. Enactment was followed by statistically significant increases in past-year suicide attempts among transgender and nonbinary youth compared with states without such laws. (PubMed)
• Kidd KM, Sequeira GM, Paglisotti T, et al. “This Could Mean Death for My Child”: Parent Perspectives on Laws Banning Gender-Affirming Care for Transgender Adolescents. J Adolesc Health. 2021;68:1082-1088.
  • Parents described fear of worsening dysphoria, suicidality, forced relocation, financial hardship, and loss of trusted clinicians if medically necessary gender affirming care became unavailable.
• Hughes LD, Kidd KM, Gamarel KE, et al. “These Laws Will Be Devastating”: Provider Perspectives on Legislation Banning Gender-Affirming Care for Transgender Adolescents. J Adolesc Health. 2021;69:976-982.
  • Clinicians providing adolescent gender care described anticipated medical and psychological harm from legislation interfering with individualized clinical decision-making.

Ethics and Clinical Decision-Making

• Kimberly LL, Folkers KM, Friesen P, et al. Ethical Issues in Gender-Affirming Care for Youth. Pediatrics. 2018;142(6):e20181537. doi:10.1542/peds.2018-1537.
  • Examines autonomy, informed consent and assent, parental involvement, fertility, uncertainty, and the ethical implications of both providing and withholding gender affirming interventions.
• Dolotina B, Turban JL. A Multipronged, Evidence-Based Approach to Improving Mental Health Among Transgender and Gender-Diverse Youth. JAMA Netw Open. 2022;5:e220926.
  • Discusses gender affirming medical care as one component of a broader approach to transgender youth mental health that also includes family support, safe schools, competent mental-health care, and reduction of discrimination.

Professional Organization Guidance

Clinical recommendations are not the same thing as primary research. They synthesize available evidence, clinical experience, patient values, and considerations such as feasibility, risks, benefits, and informed consent. Recommendations also change as evidence develops.

American Academy of Pediatrics

Rafferty J, Yogman M, Baum R, et al. Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse Children and Adolescents. Pediatrics. 2018;142(4):e20182162. doi:10.1542/peds.2018-2162.

The American Academy of Pediatrics describes a gender affirming model in which children and adolescents receive developmentally appropriate support and individualized care. For adolescents experiencing gender dysphoria, this can include puberty suppression and gender-affirming hormones after appropriate assessment and shared decision-making.

The AAP reaffirmed this policy in 2023 while authorizing a systematic review of the evidence and development of expanded clinical guidance. As of mid-2026, that updated guidance had not yet been published.

Endocrine Society

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 Metab. 2017;102(11):3869-3903. doi:10.1210/jc.2017-01658.

The Endocrine Society guideline recommends against hormonal treatment before puberty. For appropriately evaluated adolescents who have entered puberty, it recommends consideration of GnRH agonists for pubertal suppression and later gender-affirming sex hormones following multidisciplinary assessment, informed consent or assent, and fertility counseling.

The Endocrine Society continues to list this guideline as its current clinical practice guideline and reiterated its support for evidence-based gender-affirming care in subsequent statements. The guideline was cosponsored by organizations including the Pediatric Endocrine Society and European Society for Pediatric Endocrinology.

World Professional Association for Transgender Health

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 Health. 2022;23(Suppl 1):S1-S259. doi:10.1080/26895269.2022.2100644.

WPATH’s Standards of Care Version 8 include separate chapters addressing children and adolescents.

For adolescents, SOC8 recommends comprehensive biopsychosocial assessment before medical treatment, confirmation that gender incongruence is marked and sustained, assessment of the adolescent’s capacity to consent or assent, attention to mental-health concerns that could interfere with treatment, discussion of reproductive effects and fertility preservation, and involvement of caregivers when feasible and not harmful.

SOC8 does not recommend medical treatment for prepubertal children.

The recommendations were developed using literature reviews, systematic evidence reviews where considered appropriate, expert consensus, Delphi methodology, and grading of recommendations. WPATH states that the standards are intended to guide individualized clinical care rather than function as rigid treatment algorithms.

American Academy of Child and Adolescent Psychiatry

American Academy of Child and Adolescent Psychiatry. Policy Statement on Access to Gender-Affirming Healthcare. 2024.

AACAP states that transgender and gender-diverse youth should have access to multidisciplinary, evidence-based, trauma-informed, developmentally appropriate gender-affirming health care.

It supports individualized treatment plans developed collaboratively among patients, families, and clinicians and opposes legislative interference that categorically restricts access to clinically indicated care.

AACAP reaffirmed its support for gender-affirming care following the U.S. Supreme Court’s 2025 decision concerning state restrictions on care.

American Medical Association

The American Medical Association has repeatedly opposed governmental restrictions that prevent physicians and families from making individualized decisions about gender-affirming medical treatment for minors.

The AMA’s positions are policy statements rather than treatment guidelines or primary scientific evidence, but they are relevant when describing the positions of major U.S. medical organizations.

American Psychological Association

In 2024, the American Psychological Association adopted a policy supporting evidence-based, inclusive care for transgender, gender-diverse, and nonbinary people and opposing misinformation and categorical restrictions on gender-affirming care.

As with other professional-association statements, this should be distinguished from primary outcome research.

Systematic Reviews and Evidence Syntheses

Systematic reviews are particularly important in this field because individual studies are often relatively small, observational, heterogeneous in treatment protocols, and conducted in specialized clinical populations.

Systematic reviews of adolescent gender-affirming medicine have reached somewhat different conclusions despite reviewing overlapping bodies of research. Much of the disagreement reflects not whether limitations exist—they clearly do—but how observational evidence should be weighted, how study quality should be assessed, what outcomes should be considered clinically meaningful, and what degree of certainty is necessary before treatment is considered appropriate.

Puberty Suppression

• Chew D, Anderson J, Williams K, May T, Pang K. Hormonal Treatment in Young People With Gender Dysphoria: A Systematic Review. Clin Endocrinol. 2018;89(5):687-700. doi:10.1111/cen.13775.
  • This early systematic review examined puberty suppression and gender affirming hormone therapy in young people.
  • The authors found evidence of improvement in gender dysphoria, psychological functioning, and behavioral or emotional problems in some studies, but emphasized that the available literature was limited by small samples, observational study designs, and limited long-term follow-up.
  • The review called for larger and longer-term studies rather than concluding that available treatment was ineffective.
• Taylor J, Mitchell A, Hall R, Heathcote C, Langton T, Fraser L, Hewitt CE. Interventions to Suppress Puberty in Adolescents Experiencing Gender Dysphoria or Incongruence: A Systematic Review. Arch Dis Child. 2024;109(Suppl 2).
  • This review was one of the systematic reviews commissioned as part of the Cass Review.
  • The authors identified 50 studies of puberty suppression. They found consistent evidence that GnRH agonists suppress pubertal development and reported reductions in bone-density measures during treatment.
  • Evidence concerning gender dysphoria, psychological health, psychosocial functioning, cognition, cardiometabolic outcomes, and fertility was considered limited or inconsistent.
  • The authors concluded that stronger long-term research is needed to establish the benefits and risks of puberty suppression with greater certainty.
• Tornese GT, Di Mase R, Munarin J, et al. Use of Gonadotropin-Releasing Hormone Agonists in Transgender and Gender Diverse Youth: A Systematic Review. Front Endocrinol. 2025;16:1555186. doi:10.3389/fendo.2025.1555186.
  • This more recent systematic review included 51 studies examining GnRH agonists in transgender and gender-diverse youth.
  • The review found consistent evidence that GnRH agonists effectively suppress endogenous puberty. Across the literature, psychological outcomes were generally stable or improved, particularly when puberty suppression was followed by gender affirming hormone therapy.
  • The authors also emphasized continued uncertainty around long-term bone health, fertility, sexual function, and several other outcomes.
  • Rather than describing puberty suppression as either universally beneficial or harmful, the review supports its clinical effectiveness for suppressing puberty while emphasizing the need for continued longitudinal study.

Gender Affirming Hormones

Taylor J, Mitchell A, Hall R, Langton T, Fraser L, Hewitt CE. Masculinising and Feminising Hormone Interventions for Adolescents Experiencing Gender Dysphoria or Incongruence: A Systematic Review. Arch Dis Child. 2024. doi:10.1136/archdischild-2023-326670.

This Cass-commissioned systematic review identified 53 studies of gender-affirming hormone treatment.

The review found consistent evidence that testosterone and estrogen produce the intended masculinizing or feminizing physical changes.

For psychological outcomes, evidence primarily from pre/post studies showed improvement in depression, anxiety, and other measures of psychological health after approximately 12 months of treatment. The authors characterized this evidence as moderate quality but noted substantial methodological limitations.

Evidence concerning fertility, cognitive outcomes, gender dysphoria, body satisfaction, bone health, growth, and cardiometabolic outcomes was more limited or inconsistent.

The authors concluded that hormone therapy may improve psychological health, while emphasizing the need for stronger controlled and long-term studies.

Bone Health

Tienforti D, Marinelli L, Terrana G, et al. Bone Accrual During Puberty Suppression and Gender-Affirming Therapy in Transgender Adolescents: A Systematic Review and Meta-Analysis. JAMA Pediatr. Published online August 3, 2026. doi:10.1001/jamapediatrics.2026.2470.

This meta-analysis of 10 longitudinal cohorts totaling 751 adolescents provides one of the most focused quantitative assessments of skeletal outcomes currently available.

Bone-mineral-density z-scores declined during puberty suppression. After initiation of gender-affirming hormones, absolute bone density increased and z-scores partially recovered.

Some measures remained numerically below pretreatment levels, although differences were not consistently statistically significant.

The findings reinforce the importance of bone-health monitoring and avoiding unnecessarily prolonged hypogonadal states while also demonstrating continued bone accrual after gender-affirming sex steroids are initiated.

Reviews of the Reviews

Doyle DM, de Vries ALC. Systematic Reviews and the Needs of the Adolescent Transgender Health Care Field. Lancet. 2026;408(10557):861-866. doi:10.1016/S0140-6736(26)00788-9.

This 2026 Lancet Viewpoint is particularly useful for understanding why apparently similar systematic reviews have sometimes generated very different public interpretations.

The authors identified 13 systematic reviews published since 2017, including seven since 2023, examining puberty suppression and gender-affirming hormones in adolescents.

They argue that systematic reviews have appropriately identified limitations in the evidence—including observational designs, relatively small cohorts, heterogeneity, and limited long-term follow-up—but that these limitations have sometimes been translated into conclusions that extend beyond what the reviews themselves establish.

In particular, the authors distinguish between:

• evidence being uncertain;
• evidence failing to demonstrate an effect with high certainty;
• evidence demonstrating no benefit; and
• evidence demonstrating harm.

Those findings are not interchangeable.

The authors caution against using systematic-review quality ratings as simple yes/no determinations of whether treatment works or whether care should be available.

Critical Appraisal of the Cass Review and U.S. Department of Health and Human Services Report

Government-commissioned evidence reviews have become increasingly influential in adolescent transgender medicine.

Two particularly consequential examples are the United Kingdom’s 2024 Independent Review of Gender Identity Services for Children and Young People, commonly called the Cass Review, and the U.S. Department of Health and Human Services report Treatment for Pediatric Gender Dysphoria: Review of Evidence and Best Practices, initially released in May 2025 and subsequently revised following a peer-review process.

Both reports—and particularly the methods used to generate or interpret their evidence reviews—have also been subjected to substantive scientific and methodological criticism.

Critiques of the Cass Review

Noone C, Southgate A, Ashman A, et al. Critically Appraising the Cass Report: Methodological Flaws and Unsupported Claims. BMC Med Res Methodol. 2025;25:128. doi:10.1186/s12874-025-02581-7.

This is one of the most detailed peer-reviewed methodological examinations of the evidence reviews commissioned by Cass.

The researchers independently assessed the seven systematic reviews informing the Cass Review using ROBIS, an established tool specifically designed to evaluate risk of bias in systematic reviews.

They rated all seven reviews as having an overall high risk of bias.

Concerns included ambiguous eligibility criteria, deviations from the registered review protocol, use of a single largely unmodified search strategy across distinct research questions, exclusion of potentially relevant evidence, use of modified study-quality tools, and exclusion of studies categorized as low quality from some narrative syntheses.

The authors particularly questioned the decision to exclude 48% of puberty-suppression studies and 36% of hormone-treatment studies from the respective syntheses based on quality ratings derived from a modified Newcastle-Ottawa Scale.

They also evaluated primary research commissioned for the Cass Review and argued that some conclusions in the final report extended beyond what those data could establish.

Their broader concern was a possible difference in evidentiary standards: evidence supporting gender-affirming interventions was subjected to a particularly restrictive standard, while some recommendations made by the Review rested on considerably less direct evidence.

A correction published in December 2025 clarified one sentence that had conflated the authors of the Cass final report with the authors of its commissioned systematic reviews; it did not retract the paper’s primary ROBIS findings.

Grijseels DM. Biological and Psychosocial Evidence in the Cass Review: A Critical Commentary. Int J Transgend Health. 2024.

This peer-reviewed commentary examines the biological, developmental, and psychosocial claims used in the Cass Review.

The author argues that several conclusions regarding gender development, neurodevelopment, psychosocial influences, and medical treatment extend beyond the research cited in support of them.

The paper also questions whether the available evidence supports some of the Review’s recommendations for changing established treatment pathways.

McNamara M, Baker K, Connelly K, et al. An Evidence-Based Critique of “The Cass Review” on Gender-Affirming Care for Adolescent Gender Dysphoria. Yale Integrity Project. 2024.

This multidisciplinary critique was written by clinicians and researchers in adolescent medicine, endocrinology, psychiatry, epidemiology, and related fields.

It is not itself a peer-reviewed journal article, so it should be identified separately from the peer-reviewed literature.

The authors argue that the Cass Review sometimes conflates low-certainty evidence with evidence demonstrating lack of benefit, underweights existing observational and longitudinal evidence, and makes recommendations that are not always directly supported by evidence assessed in the Review.

They also emphasize an important point sometimes lost in political discussion: the Cass Review did not conclude that puberty suppression or gender-affirming hormone therapy should never be provided to adolescents.

Aaron DG, Konnoth C. The Future of Gender-Affirming Care — A Law and Policy Perspective on the Cass Review. N Engl J Med. 2025;392:526-528. doi:10.1056/NEJMp2413747.

This New England Journal of Medicine Perspective focuses particularly on the translation of Cass into U.S. law and health policy.

The authors argue that the Review’s conclusions have sometimes been used to justify categorical treatment bans even though Cass itself envisioned continued medical treatment for some adolescents.

They also emphasize structural differences between England’s National Health Service and U.S. medical practice that make direct transplantation of Cass’s service-delivery recommendations problematic.

The U.S. Department of Health and Human Services Report

In May 2025, HHS released Treatment for Pediatric Gender Dysphoria: Review of Evidence and Best Practices.

The circumstances in which the report was commissioned are important context for evaluating it.

It was ordered by Executive Order 14187, which had already directed federal agencies toward restricting gender-affirming medical treatment for people younger than 19 and explicitly characterized the scientific basis of that care negatively before the review was conducted.

The report subsequently concluded that evidence supporting adolescent gender-affirming medical treatment was of low or very low certainty and placed substantial emphasis on potential harms and alternatives to medical treatment.

The initial report did not identify its authors and had not undergone conventional external peer review before publication.

HHS subsequently conducted a review process and released a revised report and accompanying peer-review supplement in November 2025.

Accordingly, describing the current HHS document simply as “not peer reviewed” is no longer accurate. More substantive criticism concerns how evidence was selected, graded, interpreted, and translated into clinical and policy conclusions.

Peer-Reviewed Critiques of the HHS Report

Dowshen N, Baker K, Garofalo R, Chen D, Inwards-Breland DJ, Sequeira G, Mehringer JE, McNamara M. A Critical Scientific Appraisal of the Health and Human Services Report on Pediatric Gender Dysphoria. J Adolesc Health. 2025;77(3):342-345. doi:10.1016/j.jadohealth.2025.06.002.

This critique was written by clinicians and researchers with expertise in adolescent medicine and transgender health.

The authors raise concerns about selective presentation of evidence, treatment of observational research as inherently inadequate, omission or minimization of studies reporting favorable clinical outcomes, and reliance on some sources that were not peer reviewed.

A central criticism is the report’s treatment of certainty of evidence.

Low-certainty evidence means that additional research could materially change an estimate of effect. It does not mean that research has demonstrated that a treatment does not work.

The authors argue that this distinction is not consistently preserved in the HHS report.

Rider GN, Weideman BCD, Ehrensaft D, et al. Scientific Integrity and Pediatric Gender Healthcare: Disputing the HHS Review. Sex Res Soc Policy. 2025. doi:10.1007/s13178-025-01221-5.

This peer-reviewed commentary provides a broader methodological and scientific critique of the HHS review.

The authors argue that HHS places excessive weight on the traditional hierarchy of evidence and the absence of randomized trials while inadequately considering how evidence is generated in pediatric medicine when randomized trials are difficult, impractical, or ethically complicated.

They emphasize that gender-affirming adolescent medicine includes multiple prospective longitudinal cohorts rather than only cross-sectional evidence.

The authors also criticize HHS’s reliance on the Cass Review without substantively incorporating several published critiques of the Cass methodology.

Another concern is contextual: the original HHS review was commissioned by an executive order whose stated policy objective preceded the scientific review.

That does not by itself establish that every conclusion in the report is incorrect, but it makes methodological transparency and independence particularly important when interpreting the report.