{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:48:15Z","timestamp":1790484495632,"version":"4.1.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>In the US, transgender, nonbinary, and gender diverse (TGD) adults have high rates of depression. Gender-affirming hormone therapy (GAHT) is associated with improved mental health outcomes, yet existing US studies have short follow ups and lack sample diversity.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the use of GAHT delivered in primary care as an intervention for moderate-to-severe depressive symptoms in diverse TGD adult patients.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>LEGACY was an observational cohort study conducted in federally qualified community health centers in Boston and New York that followed up TGD patients (N\u2009=\u20093592) from calendar years 2016 to 2019 (48 months). Participants included individuals aged 18 years or older, gender identity different from sex at birth, a past 12-month medical visit, and signed patient consent form in the electronic health record (EHR).<\/jats:p><\/jats:sec>Exposures<\/jats:title>Prescriptions for GAHT obtained from EHR data, using the date of the first and last GAHT prescription in each calendar year of observation (GAHT within the year vs no GAHT during the year).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>A binary outcome of patient-reported moderate-to-severe depressive symptoms was obtained using the validated Patient-Health Questionnaire (PHQ), scoring 10 or greater on the PHQ-9 or scoring 3 or greater on the PHQ-2. Following multiple imputation, generalized estimating equations (GEE) longitudinally modeled GAHT and moderate-to-severe depressive symptoms (n = 20 320 observations) and adjusted for age, gender identity, race and ethnicity, health insurance, federal poverty level, HIV serostatus, number of cohort years, and clinical site.<\/jats:p><\/jats:sec>Results<\/jats:title>The median age of the 3592 patients was 28 (IQR, 24-36) years. Race and ethnicity was diverse (1.3% Asian\/Pacific Islander, 11.7% Black, 16.1% Hispanic\/Latinx, 63.1% White, 6.8% multiracial, and 1.4% other). In addition, 18.9% were nonbinary, 52.1% lived below the federal poverty level, 34.2% were publicly insured, 4.1% were uninsured, and 5.1% were living with HIV. At baseline, 84.5% of the individuals were prescribed GAHT and 15.3% reported moderate-to-severe depressive symptoms. Patients prescribed GAHT had a statistically significantly lower risk of moderate-to-severe depressive symptoms over follow-up compared with those not prescribed GAHT (adjusted risk ratio, 0.85; 95% CI, \u20090.75-0.98).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this longitudinal observational cohort study, GAHT was associated with lower rates of moderate-to-severe depressive symptoms, highlighting the importance of gender-affirming primary care models for TGD patients.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.0955","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T15:31:56Z","timestamp":1742225516000},"page":"e250955","source":"Crossref","is-referenced-by-count":25,"title":["Gender-Affirming Hormone Therapy and Depressive Symptoms Among Transgender Adults"],"prefix":"10.1001","volume":"8","author":[{"given":"Sari L.","family":"Reisner","sequence":"first","affiliation":[{"name":"Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor"},{"name":"Center for Social Epidemiology and Population Health, University of Michigan, Ann Arbor"},{"name":"Eisenberg Family Depression Center, University of Michigan, Ann Arbor"},{"name":"Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"},{"name":"The Fenway Institute, Fenway Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Pletta","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex S.","family":"Keuroghlian","sequence":"additional","affiliation":[{"name":"The Fenway Institute, Fenway Health, Boston, Massachusetts"},{"name":"Department of Psychiatry, Massachusetts General Hospital, Boston\/Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth H.","family":"Mayer","sequence":"additional","affiliation":[{"name":"The Fenway Institute, Fenway Health, Boston, Massachusetts"},{"name":"Department of Medicine, Beth Israel Deaconess Medical Center\/Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline B.","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Family Community Medicine, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Potter","sequence":"additional","affiliation":[{"name":"The Fenway Institute, Fenway Health, Boston, Massachusetts"},{"name":"Department of Medicine, Beth Israel Deaconess Medical Center\/Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn M. W.","family":"Hughto","sequence":"additional","affiliation":[{"name":"The Fenway Institute, Fenway Health, Boston, Massachusetts"},{"name":"Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, Rhode Island"},{"name":"Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island"},{"name":"Center for Health Promotion and Health Equity, Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Harris","sequence":"additional","affiliation":[{"name":"Callen-Lorde Community Health Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asa E.","family":"Radix","sequence":"additional","affiliation":[{"name":"Callen-Lorde Community Health Center, New York, New York"},{"name":"Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"issue":"24","key":"zoi250071r1","doi-asserted-by":"publisher","first-page":"644","DOI":"10.15585\/mmwr.mm7224a1","article-title":"National, state-level, and county-level prevalence estimates of adults aged =18 years self-reporting a lifetime diagnosis of depression\u2014United States, 2020.","volume":"72","author":"Lee","year":"2023","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"10","key":"zoi250071r2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.37011","article-title":"Depressive symptoms and mortality among US adults.","volume":"6","author":"Zhang","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"4","key":"zoi250071r5","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1001\/jama.2015.18392","article-title":"Screening for depression in adults: US Preventive Services Task Force recommendation statement.","volume":"315","author":"Siu","year":"2016","journal-title":"JAMA"},{"issue":"23","key":"zoi250071r6","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1001\/jama.2023.9297","article-title":"Screening for depression and suicide risk in adults: US Preventive Services Task Force recommendation statement.","volume":"329","author":"Barry","year":"2023","journal-title":"JAMA"},{"issue":"3","key":"zoi250071r7","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1001\/jamapsychiatry.2015.3281","article-title":"US Preventive Services Task Force recommendation statement on screening for depression in adults: not good enough.","volume":"73","author":"Reynolds","year":"2016","journal-title":"JAMA Psychiatry"},{"issue":"10042","key":"zoi250071r8","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/S0140-6736(16)00684-X","article-title":"Global health burden and needs of transgender populations: a review.","volume":"388","author":"Reisner","year":"2016","journal-title":"Lancet"},{"issue":"3","key":"zoi250071r9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0299373","article-title":"Health status of transgender people globally: a systematic review of research on disease burden and correlates.","volume":"19","author":"Scheim","year":"2024","journal-title":"PLoS One"},{"issue":"4","key":"zoi250071r10","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab011","article-title":"Hormone therapy, mental health, and quality of life among transgender people: a systematic review.","volume":"5","author":"Baker","year":"2021","journal-title":"J Endocr Soc"},{"issue":"1","key":"zoi250071r11","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1089\/trgh.2015.0008","article-title":"A systematic review of the effects of hormone therapy on psychological functioning and quality of life in transgender individuals.","volume":"1","author":"White Hughto","year":"2016","journal-title":"Transgend Health"},{"issue":"8","key":"zoi250071r12","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1038\/s41562-023-01605-w","article-title":"A systematic review of psychosocial functioning changes after gender-affirming hormone therapy among transgender people.","volume":"7","author":"Doyle","year":"2023","journal-title":"Nat Hum Behav"},{"issue":"1","key":"zoi250071r13","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1089\/trgh.2020.0094","article-title":"The effect of gender-affirming hormones on gender dysphoria, quality of life, and psychological functioning in transgender individuals: a systematic review.","volume":"8","author":"van Leerdam","year":"2023","journal-title":"Transgend Health"},{"issue":"12","key":"zoi250071r14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0260063","article-title":"The worldwide burden of HIV in transgender individuals: an updated systematic review and meta-analysis.","volume":"16","author":"Stutterheim","year":"2021","journal-title":"PLoS One"},{"key":"zoi250071r15","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1080\/26895269.2022.2100644","article-title":"Standards of care for the health of transgender and gender diverse people, version 8.","volume":"23","author":"Coleman","year":"2022","journal-title":"Int J Transgend Health"},{"issue":"3","key":"zoi250071r16","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1007\/s11524-015-9947-2","article-title":"Comprehensive transgender healthcare: the gender affirming clinical and public health model of Fenway Health.","volume":"92","author":"Reisner","year":"2015","journal-title":"J Urban Health"},{"issue":"1","key":"zoi250071r17","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1186\/s12874-021-01328-4","article-title":"Patient-centered practices for engaging transgender and gender diverse patients in clinical research studies.","volume":"21","author":"Asquith","year":"2021","journal-title":"BMC Med Res Methodol"},{"issue":"1","key":"zoi250071r18","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1186\/s12889-022-14139-z","article-title":"\u201cFocus more on what\u2019s right instead of what\u2019s wrong:\u201d research priorities identified by a sample of transgender and gender diverse community health center patients.","volume":"22","author":"LeBlanc","year":"2022","journal-title":"BMC Public Health"},{"issue":"3","key":"zoi250071r19","doi-asserted-by":"publisher","DOI":"10.2196\/24198","article-title":"Longitudinal cohort study of gender affirmation and HIV-related health in transgender and gender diverse adults: the LEGACY Project protocol.","volume":"10","author":"Reisner","year":"2021","journal-title":"JMIR Res Protoc"},{"issue":"4","key":"zoi250071r20","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"61","author":"von Elm","year":"2008","journal-title":"J Clin Epidemiol"},{"issue":"9","key":"zoi250071r21","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","article-title":"The PHQ-9: validity of a brief depression severity measure.","volume":"16","author":"Kroenke","year":"2001","journal-title":"J Gen Intern Med"},{"issue":"11","key":"zoi250071r22","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1097\/01.MLR.0000093487.78664.3C","article-title":"The Patient Health Questionnaire-2: validity of a two-item depression screener.","volume":"41","author":"Kroenke","year":"2003","journal-title":"Med Care"},{"issue":"11","key":"zoi250071r24","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1097\/QAD.0000000000000647","article-title":"Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm.","volume":"29","author":"Haberer","year":"2015","journal-title":"AIDS"},{"issue":"2","key":"zoi250071r26","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.0184","article-title":"Assessing missing data assumptions in EHR-based studies: a complex and underappreciated task.","volume":"4","author":"Haneuse","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"3","key":"zoi250071r27","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1177\/0962280206074463","article-title":"Multiple imputation of discrete and continuous data by fully conditional specification.","volume":"16","author":"van Buuren","year":"2007","journal-title":"Stat Methods Med Res"},{"issue":"3","key":"zoi250071r28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v045.i03","article-title":"mice: Multivariate imputation by chained equations in R.","volume":"45","author":"van Buuren","year":"2011","journal-title":"J Stat Softw"},{"issue":"1","key":"zoi250071r29","doi-asserted-by":"publisher","first-page":"121","DOI":"10.2307\/2531248","article-title":"Longitudinal data analysis for discrete and continuous outcomes.","volume":"42","author":"Zeger","year":"1986","journal-title":"Biometrics"},{"issue":"4","key":"zoi250071r30","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.2307\/2531734","article-title":"Models for longitudinal data: a generalized estimating equation approach.","volume":"44","author":"Zeger","year":"1988","journal-title":"Biometrics"},{"issue":"1","key":"zoi250071r32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2307\/1403572","article-title":"A comparison of cluster-specific and population-averaged approaches for analyzing correlated binary data.","volume":"59","author":"Neuhaus","year":"1991","journal-title":"Int Stat Rev"},{"issue":"4","key":"zoi250071r33","doi-asserted-by":"publisher","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity analysis in observational research: introducing the E-Value.","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann Intern Med"},{"issue":"5","key":"zoi250071r34","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1097\/EDE.0000000000000864","article-title":"Web site and R package for computing E-values.","volume":"29","author":"Mathur","year":"2018","journal-title":"Epidemiology"},{"issue":"5","key":"zoi250071r35","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1176\/ajp.137.5.535","article-title":"The clinical application of the biopsychosocial model.","volume":"137","author":"Engel","year":"1980","journal-title":"Am J Psychiatry"},{"issue":"Suppl 3","key":"zoi250071r36","doi-asserted-by":"publisher","first-page":"S235","DOI":"10.1097\/QAI.0000000000001088","article-title":"Integrated and gender-affirming transgender clinical care and research.","volume":"72","author":"Reisner","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"Suppl 3","key":"zoi250071r37","doi-asserted-by":"publisher","first-page":"S210","DOI":"10.1097\/QAI.0000000000001087","article-title":"Global epidemiology of HIV infection and related syndemics affecting transgender people.","volume":"72","author":"Poteat","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"8","key":"zoi250071r41","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1001\/jamainternmed.2024.2544","article-title":"Health status and mental health of transgender and gender-diverse adults.","volume":"184","author":"Liu","year":"2024","journal-title":"JAMA Intern Med"},{"issue":"10","key":"zoi250071r42","doi-asserted-by":"publisher","first-page":"2922","DOI":"10.1007\/s11606-021-06746-0","article-title":"FQHC designation and safety net patient revenue associated with primary care practice capabilities for access and quality.","volume":"36","author":"Lewis","year":"2021","journal-title":"J Gen Intern Med"},{"issue":"11","key":"zoi250071r43","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1001\/journalofethics.2016.18.11.stas1-1611","article-title":"What\u2019s in a guideline? developing collaborative and sound research designs that substantiate best practice recommendations for transgender health Care.","volume":"18","author":"Deutsch","year":"2016","journal-title":"AMA J Ethics"},{"key":"zoi250071r44","doi-asserted-by":"publisher","DOI":"10.1016\/j.socscimed.2023.116290","article-title":"Better outcomes through patient-provider therapeutic connections? an exploratory study of proposed mediating variables.","volume":"338","author":"Rathert","year":"2023","journal-title":"Soc Sci Med"},{"key":"zoi250071r31","volume-title":"Multiple Imputation for Nonresponse in Surveys","author":"Rubin","year":"2004"},{"key":"zoi250071r3","unstructured":"Substance Abuse and Mental Health Services Administration (SAMHSA). Key substance use and mental health indicators in the United States: results from the 2021 National Survey on Drug Use and Health (HHS publication No. PEP22-07-01-005, NSDUH Series H-57). 2022. Accessed July 20, 2024. https:\/\/www.samhsa.gov\/data\/report\/2021-nsduh-annual-national-report"},{"key":"zoi250071r4","unstructured":"Centers for Disease Control and Prevention (CDC). Symptoms of depression among adults: United States, 2019 (National Center for Health Statistics Data Brief No. 379). 2020. Accessed July 20, 2024. https:\/\/www.cdc.gov\/nchs\/products\/databriefs\/db379.htm"},{"key":"zoi250071r23","unstructured":"US Department of Health and Human Services (HHS). Federal poverty level (FPL). 2022. Accessed July 10, 2024. https:\/\/www.healthcare.gov\/glossary\/federal-poverty-level-fpl\/"},{"key":"zoi250071r25","unstructured":"Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2024. Accessed July 10, 2024. https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/adult-and-adolescent-arv"},{"key":"zoi250071r38","unstructured":"The White House. National HIV\/AIDS strategy for the United States 2022\u20132025. 2021. Accessed July 10, 2024. https:\/\/files.hiv.gov\/s3fs-public\/NHAS-2022-2025.pdf"},{"key":"zoi250071r39","unstructured":"Movement Advancement Project. Equality maps: Snapshot: LGBTQ equality by state. 2024. Accessed September 8, 2024. https:\/\/www.mapresearch.org\/equality-maps\/"},{"key":"zoi250071r40","unstructured":"Trans Legislation Tracker. Tracking the rise of anti-trans bills in the US. 2024. Accessed September 9, 2024. https:\/\/translegislation.com\/"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2831643\/reisner_2025_oi_250071_1741626314.27797.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T15:32:00Z","timestamp":1742225520000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2831643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,3]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2025.0955","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]}}}