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Gender-affirming hormone therapy and suicide-related outcomes in transgender and gender-diverse populations: a systematic review and meta-analysis

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Published: 10 April 2026
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This systematic review and meta-analysis examined the association between gender-affirming hormone therapy (GAHT) and suicide-related outcomes (including suicidal ideation, suicide attempt, and suicide death) among transgender and gender-diverse individuals. It included 8 independent studies with 11 effect sizes. The pooled multilevel estimate was not statistically significant but pointed in a negative direction (log odds ratio = -0.3576; 95% confidence interval: -1.2768 to 0.5617; p=0.4458), suggesting a possible but not definitive protective effect of GAHT against suicidality. There was substantial heterogeneity among studies [Q (10)=170.5309, p<0.0001; σ2=1.7820; I2≈94.1%]. Moderator analyses showed that age group was significant [QM (2)=6.9350, p=0.0312], with mixed-age samples differing from adolescent samples, but adult samples did not significantly differ from adolescent samples. Comparator type, study design, and outcome domain were not significant moderators. Sensitivity analyses pointed to influential studies and evidence of funnel asymmetry and small-study effects. The conclusions highlight that while there is a non-significant trend toward a protective effect of GAHT, the evidence is limited by high heterogeneity, influential studies, small-study effects, and the predominantly observational nature of the data. Larger and better-characterized longitudinal studies are needed for clearer causal inference.

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Bretherton I, Thrower E, Zwickl S, et al. The health and well-being of transgender Australians: a national community survey. LGBT Health 2021;8:42-9.
Clements-Nolle K, Marx R, Katz M. Attempted suicide among transgender persons: The influence of gender-based discrimination and victimization. J Homosex 2006;51:53-69.
Maguen S, Shipherd JC. Suicide risk among transgender individuals. Psychology Sexuality 2010;1:34-43.
Herman JL, Flores AR, Brown TN, et al. Age of individuals who identify as transgender in the United States. Los Angeles, CA, USA: The Williams Institute; 2017.
T’Sjoen G, Arcelus J, Gooren L, et al. Endocrinology of transgender medicine. Endocr Rev 2019;40:97-117.
Clark TC, Lucassen MF, Bullen P, et al. The health and well-being of transgender high school students: results from the New Zealand adolescent health survey (Youth’12). J Adolesc Health 2014;55:93-9.
Strauss P, Cook A, Winter S, et al. Trans pathways: the mental health experiences and care pathways of trans young people. Summary of results. Perth, Australia: Telethon Kids Institute; 2017
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 Morb Mortal Wkly Rep 2019;68:67-71.
Kaltiala-Heino R, Lindberg N. Gender identities in adolescent population: methodological issues and prevalence across age groups. Eur Psychiatry 2019;55:61-6.
White AA, Lin A, Bickendorf X, et al. Potential immunological effects of gender-affirming hormone therapy in transgender people–an unexplored area of research. Ther Adv Endocrinol Metab 2022;13:20420188221139612.
Wiepjes CM, Nota NM, de Blok CJ, et al. The Amsterdam cohort of gender dysphoria study (1972–2015): trends in prevalence, treatment, and regrets. J Sex Med 2018;15:582-90.
Adams N, Hitomi M, Moody C. Varied reports of adult transgender suicidality: Synthesizing and describing the peer-reviewed and gray literature. Transgend Health 2017;2:60-75.
Rosenthal SM. Challenges in the care of transgender and gender-diverse youth: an endocrinologist’s view. Nat Rev Endocrinol 2021;17:581-91.
Bränström R, Stormbom I, Bergendal M, Pachankis JE. Transgender‐based disparities in suicidality: A population‐based study of key predictions from four theoretical models. Suicide Life Threat Behav 2022;52:401-12.
Testa RJ, Michaels MS, Bliss W, et al. Suicidal ideation in transgender people: Gender minority stress and interpersonal theory factors. J Abnorm Psychol 2017;126:125-36.
Romanelli M, Lu W, Lindsey MA. Examining mechanisms and moderators of the relationship between discriminatory health care encounters and attempted suicide among US transgender help-seekers. Adm Policy Ment Health 2018;45:831-49.
Bird K, Arcelus J, Matsagoura L, et al. Risk and protective factors for self-harm thoughts and behaviours in transgender and gender diverse people: a systematic review. Heliyon 2024;10:e26074.
Ünsal BC, Demetrovics Z, Reinhardt M. Gender minority stressors, hopelessness, and their associations with internalizing and externalizing mental health outcomes in a Hungarian trans adult sample. Arch Sex Behav 2025;54:1859-74.
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:S1-259.
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;102:3869-903.
Budge SL, Adelson JL, Howard KA. Anxiety and depression in transgender individuals: the roles of transition status, loss, social support, and coping. J Consult Clin Psychol 2013;81:545-57.
World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th ed. 2011. Available from: https://www.cpath.ca/wp-content/uploads/2009/12/Standards-of-Care-V7-2011-WPATH.pdf
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;8:2276-83.
Turban JL, King D, Carswell JM, Keuroghlian AS. Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation. Pediatrics 2020;145:e20191725.
Ciancia S, Dubois V, Cools M. Impact of gender-affirming treatment on bone health in transgender and gender diverse youth. Endocr Connect 2022;11:e220280.
Klink D, Caris M, Heijboer A, et al. Bone mass in young adulthood following gonadotropin-releasing hormone analog treatment and cross-sex hormone treatment in adolescents with gender dysphoria. J Clin Endocrinol Metab 2015;100:E270-5.
Schagen SEE, Wouters FM, Cohen-Kettenis PT, et al. Bone development in transgender adolescents treated with GnRH analogues and subsequent gender-affirming hormones. J Clin Endocrinol Metab 2020;105:e4252-63.
Irwig MS. Testosterone therapy for transgender men. Lancet Diabetes Endocrinol 2017;5:301-11.
Tangpricha V, den Heijer M. Oestrogen and anti-androgen therapy for transgender women. Lancet Diabetes Endocrinol 2017;5:291-300.
Baker KE, Wilson LM, Sharma R, et al. Hormone therapy, mental health, and quality of life among transgender people: a systematic review. J Endocr Soc 2021;5:bvab011.
Costa R, Colizzi M. The effect of cross-sex hormonal treatment on gender dysphoria individuals’ mental health: a systematic review. Neuropsychiatr Dis Treat 2016;12:1953-66.
White Hughto JM, Reisner SL. A systematic review of the effects of hormone therapy on psychological functioning and quality of life in transgender individuals. Transgend Health 2016;1:21-31.
Nolan BJ, Zwickl S, Locke P, et al. Early access to testosterone therapy in transgender and gender-diverse adults seeking masculinization: a randomized clinical trial. JAMA Netw Open 2023;6:e2331919.
Buncamper ME, van der Sluis WB, van der Pas RSD, et al. Surgical outcome after penile inversion vaginoplasty: a retrospective study of 475 transgender women. Plast Reconstr Surg 2016;138:999-1007.
Hontscharuk R, Alba B, Hamidian Jahromi A, Schechter L. Penile inversion vaginoplasty outcomes: Complications and satisfaction. Andrology 2021;9:1732-43.
Papadopulos NA, Lellé JD, Zavlin D, et al. Quality of life and patient satisfaction following male-to-female sex reassignment surgery. J Sex Med 2017;14:721-30.
Klassen AF, Kaur M, Johnson N, et al. International phase I study protocol to develop a patient-reported outcome measure for adolescents and adults receiving gender-affirming treatments (the GENDER-Q). BMJ Open 2018;8:e025435.
van der Sluis WB, Schäfer T, Nijhuis THJ, Bouman MB. Genital gender-affirming surgery for transgender women. Best Pract Res Clin Obstet Gynaecol 2023;86:102297.
Tordoff DM, Wanta JW, Collin A, et al. Mental health outcomes in transgender and nonbinary youths receiving gender-affirming care. JAMA Netw Open 2022;5:e220978.
Shelemy L, Cotton S, Crane C, Knight M. Systematic review of prospective adult mental health outcomes following affirmative interventions for gender dysphoria. Int J Transgend Health 2024;26:480-500.
Bränström R, Pachankis JE. Reduction in mental health treatment utilization among transgender individuals after gender-affirming surgeries: a total population study. Am J Psychiatry 2020;177:727-34.
Campbell T, Mann S, Rodgers YVM, Tran NM. Mental health of transgender youth following gender identity milestones by level of family support. JAMA Pediatr 2024;178:870-8.
Boase ER, McLaren S. Discrimination and suicide risk among transgender and gender-diverse adults: The moderating roles of self-compassion, self-coldness, and gender identity. Psychol Sex Orientat Gend Divers 2024;11:606-18.
Dahlen S, Connolly D, Arif I, et al. International clinical practice guidelines for gender minority/trans people: systematic review and quality assessment. BMJ Open 2021;11:e048943.
Zwickl S, Wong AFQ, Dowers E, et al. Factors associated with suicide attempts among Australian transgender adults. BMC Psychiatry 2021;21:81.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71.
Rethlefsen ML, Kirtley S, Waffenschmidt S, et al. PRISMA-S: an extension to the PRISMA statement for reporting literature searches in systematic reviews. J Med Libr Assoc 2021;109:174-200.
Sterne JA, Sutton AJ, Ioannidis JP, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011;343:d4002.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539-58.
Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw 2010;36:1-48.
Konstantopoulos S. Fixed effects and variance components estimation in three-level meta-analysis. Res Synth Methods 2011;2:61-76.
Baujat B, Mahé C, Pignon JP, Hill C. A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials. Stat Med 2002;21:2641-52.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.
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;70:643-9.
Hughto JMW, Gunn HA, Rood BA, Pantalone DW. Social and medical gender affirmation experiences are inversely associated with mental health problems in a U.S. non-probability sample of transgender adults. Arch Sex Behav 2020;49:2635-47.
Summers NA, Huynh TT, Dunn RC, et al. Effects of gender-affirming hormone therapy on progression along the HIV care continuum in transgender women. Open Forum Infect Dis 2021;8:ofab404.
Colizzi M, Costa R, Todarello O. Transsexual patients’ psychiatric comorbidity and positive effect of cross-sex hormonal treatment on mental health: results from a longitudinal study. Psychoneuroendocrinology 2014;39:65-73.
Tucker RP, Testa RJ, Simpson TL, et al. Hormone therapy, gender affirmation surgery, and their association with recent suicidal ideation and depression symptoms in transgender veterans. Psychol Med 2018;48:2329-36.

How to Cite



1.
Gender-affirming hormone therapy and suicide-related outcomes in transgender and gender-diverse populations: a systematic review and meta-analysis. Mental Wellness [Internet]. 2026 Apr. 10 [cited 2026 Apr. 11];4. Available from: https://www.mental-wellness-journal.net/mw/article/view/42