{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:48:25Z","timestamp":1792018105316,"version":"4.4.0"},"reference-count":44,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This retrospective, longitudinal cohort study used\n International Classification of Diseases, Ninth Revision<\/jats:italic>\n and\n International Statistical Classification of Diseases and Related Health Problems, Tenth Revision<\/jats:italic>\n diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component\u2013related data were available. Transgender veterans were matched to cisgender referents.\n <\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Gender-affirming hormone treatment.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), followed by cisgender females (108.3% [27.5%];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), cisgender males (49.3% [27.5%];\n P<\/jats:italic>\n \u2009=\u2009.02), and transfeminine persons (3.0% [10.7%];\n P<\/jats:italic>\n \u2009=\u2009.77).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.19696","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T11:41:30Z","timestamp":1719920490000},"page":"e2419696","source":"Crossref","is-referenced-by-count":25,"title":["Gender-Affirming Hormone Treatment and Metabolic Syndrome Among Transgender Veterans"],"prefix":"10.1001","volume":"7","author":[{"given":"Leila","family":"Hashemi","sequence":"first","affiliation":[{"name":"VA Greater Los Angeles Health Care System, Department of General Internal Medicine, David Geffen School of Medicine, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriana","family":"Marijic Buljubasic","sequence":"additional","affiliation":[{"name":"Yale School of Public Health, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Budoff","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lundquist Institute at Harbor-UCLA, Torrance, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel A.","family":"Copeland","sequence":"additional","affiliation":[{"name":"VA Central Western Massachusetts Health Care System, Leeds"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Statistics Core, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guneet K.","family":"Jasuja","sequence":"additional","affiliation":[{"name":"Center for Healthcare Organization & Implementation Research, US Department of Veterans Affairs, VA Bedford Health Care System, Bedford, Massachusetts"},{"name":"Section of General Internal Medicine, Chobanian and Avedisian School of Medicine, Boston University, Boston, Massachusetts"},{"name":"Department of Health Law, Policy and Management, School of Public Health, Boston University, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery","family":"Gornbein","sequence":"additional","affiliation":[{"name":"Statistics Core, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Reue","sequence":"additional","affiliation":[{"name":"Human Genetics, David Geffen School of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"issue":"2","key":"zoi240636r1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1080\/26895269.2020.1753136","article-title":"Epidemiological considerations in transgender health: a systematic review with focus on higher quality data.","volume":"21","author":"Zhang","year":"2020","journal-title":"Int J Transgend Health"},{"issue":"2","key":"zoi240636r2","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.2105\/AJPH.2016.303578","article-title":"Transgender population size in the United States: a meta-regression of population-based probability samples.","volume":"107","author":"Meerwijk","year":"2017","journal-title":"Am J Public Health"},{"issue":"4","key":"zoi240636r4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S2213-8587(16)30319-9","article-title":"Oestrogen and anti-androgen therapy for transgender women.","volume":"5","author":"Tangpricha","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"zoi240636r5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1475-2840-10-11","article-title":"\u201cThe metabolic syndrome...is dead\u201d: these reports are an exaggeration.","volume":"10","author":"Tenenbaum","year":"2011","journal-title":"Cardiovasc Diabetol"},{"issue":"4","key":"zoi240636r6","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1097\/00132577-200512000-00018","article-title":"Diagnosis and management of the metabolic syndrome: an American Heart Association\/National Heart, Lung, and Blood Institute scientific statement: executive summary.","volume":"4","author":"Grundy","year":"2005","journal-title":"Crit Pathw Cardiol"},{"issue":"2","key":"zoi240636r7","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.metabol.2013.10.006","article-title":"An examination of sex and racial\/ethnic differences in the metabolic syndrome among adults: a confirmatory factor analysis and a resulting continuous severity score.","volume":"63","author":"Gurka","year":"2014","journal-title":"Metabolism"},{"key":"zoi240636r8","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1475-2840-11-128","article-title":"A confirmatory factor analysis of the metabolic syndrome in adolescents: an examination of sex and racial and ethnic differences.","volume":"11","author":"Gurka","year":"2012","journal-title":"Cardiovasc Diabetol"},{"key":"zoi240636r9","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.metabol.2018.01.015","article-title":"Use of BMI as the marker of adiposity in a metabolic syndrome severity score: derivation and validation in predicting long-term disease outcomes.","volume":"83","author":"Gurka","year":"2018","journal-title":"Metabolism"},{"issue":"1-3","key":"zoi240636r10","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jsbmb.2009.12.005","article-title":"Central effects of estradiol in the regulation of food intake, body weight, and adiposity.","volume":"122","author":"Brown","year":"2010","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"2","key":"zoi240636r11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057458","article-title":"Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action.","volume":"8","author":"Matic","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"zoi240636r12","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.ygcen.2010.01.006","article-title":"Female mice and rats exhibit species-specific metabolic and behavioral responses to ovariectomy.","volume":"166","author":"Witte","year":"2010","journal-title":"Gen Comp Endocrinol"},{"issue":"5","key":"zoi240636r13","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/ncpendmet0477","article-title":"Recognizing rare disorders: aromatase deficiency.","volume":"3","author":"Jones","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab"},{"issue":"3","key":"zoi240636r14","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.maturitas.2009.11.004","article-title":"Menopause is an independent predictor of metabolic syndrome in Iranian women.","volume":"65","author":"Eshtiaghi","year":"2010","journal-title":"Maturitas"},{"issue":"6","key":"zoi240636r15","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/oby.2002.59","article-title":"Fat distribution and insulin sensitivity in postmenopausal women: influence of hormone replacement.","volume":"10","author":"Munoz","year":"2002","journal-title":"Obes Res"},{"issue":"2","key":"zoi240636r16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1515\/hmbci-2014-0002","article-title":"Sex hormone imbalances and adipose tissue dysfunction impacting on metabolic syndrome; a paradigm for the discovery of novel adipokines.","volume":"17","author":"Zhang","year":"2014","journal-title":"Horm Mol Biol Clin Investig"},{"issue":"2","key":"zoi240636r17","first-page":"63","article-title":"Correlation between hormonal statuses and metabolic syndrome in postmenopausal women.","volume":"7","author":"Ziaei","year":"2013","journal-title":"J Family Reprod Health"},{"issue":"8","key":"zoi240636r18","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.jacc.2013.01.079","article-title":"Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications.","volume":"62","author":"Martin","year":"2013","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"zoi240636r19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.tem.2006.01.004","article-title":"Of mice and men: the evolving phenotype of aromatase deficiency.","volume":"17","author":"Jones","year":"2006","journal-title":"Trends Endocrinol Metab"},{"issue":"4","key":"zoi240636r20","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1111\/obr.v19.4","article-title":"Testosterone a key factor in gender related metabolic syndrome.","volume":"19","author":"Bianchi","year":"2018","journal-title":"Obes Rev"},{"issue":"6","key":"zoi240636r21","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1111\/apa.2011.100.issue-6","article-title":"Insulin resistance and metabolic syndrome in prepubertal boys with Klinefelter syndrome.","volume":"100","author":"Bardsley","year":"2011","journal-title":"Acta Paediatr"},{"issue":"11","key":"zoi240636r22","doi-asserted-by":"publisher","first-page":"5688","DOI":"10.1172\/JCI140223","article-title":"X chromosome dosage of histone demethylase KDM5C determines sex differences in adiposity.","volume":"130","author":"Link","year":"2020","journal-title":"J Clin Invest"},{"issue":"8","key":"zoi240636r23","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1161\/ATVBAHA.115.305460","article-title":"Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes.","volume":"35","author":"Link","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"zoi240636r24","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1007\/978-3-319-70178-3","article-title":"Sex, gender, and transgender: metabolic impact of cross hormone therapy.","volume":"1043","author":"de Souza Santos","year":"2017","journal-title":"Adv Exp Med Biol"},{"issue":"9","key":"zoi240636r25","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1093\/aje\/kwab102","article-title":"Validating data-driven methods to identify transgender individuals in the Veterans Health Administration of the US Department of Veterans Affairs.","volume":"190","author":"Wolfe","year":"2021","journal-title":"Am J Epidemiol"},{"issue":"8","key":"zoi240636r27","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1097\/01.mlr.0000218786.44722.14","article-title":"Effect of using information from only one system for dually eligible health care users.","volume":"44","author":"Byrne","year":"2006","journal-title":"Med Care"},{"issue":"9","key":"zoi240636r28","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.2337\/diacare.28.9.2289","article-title":"The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes.","volume":"28","author":"Kahn","year":"2005","journal-title":"Diabetes Care"},{"issue":"6","key":"zoi240636r29","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1007\/BF00403180","article-title":"Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome.","volume":"34","author":"Ferrannini","year":"1991","journal-title":"Diabetologia"},{"issue":"20","key":"zoi240636r30","first-page":"S635","article-title":"The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance.","volume":"8","author":"Kendall","year":"2002","journal-title":"Am J Manag Care"},{"issue":"5","key":"zoi240636r31","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.3390\/jcm9051278","article-title":"Sexual dimorphism of NAFLD in adults.","volume":"9","author":"Lonardo","year":"2020","journal-title":"J Clin Med"},{"issue":"6","key":"zoi240636r32","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1210\/jc.2018-02138","article-title":"Cardiometabolic effects of testosterone in transmen and estrogen plus cyproterone acetate in transwomen.","volume":"104","author":"van Velzen","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"zoi240636r33","doi-asserted-by":"publisher","first-page":"3914","DOI":"10.1210\/jc.2017-01643","article-title":"Sex steroids and cardiovascular outcomes in transgender individuals: a systematic review and meta-analysis.","volume":"102","author":"Maraka","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"zoi240636r35","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1210\/jc.2017-01559","article-title":"Effects of sex hormone treatment on the metabolic syndrome in transgender individuals: focus on metabolic cytokines.","volume":"103","author":"Auer","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"zoi240636r36","doi-asserted-by":"publisher","first-page":"37005","DOI":"10.1038\/srep37005","article-title":"12-Months metabolic changes among gender dysphoric individuals under cross-sex hormone treatment: a targeted metabolomics study.","volume":"6","author":"Auer","year":"2016","journal-title":"Sci Rep"},{"issue":"4","key":"zoi240636r37","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1089\/met.2010.0008","article-title":"Ability among adolescents for the metabolic syndrome to predict elevations in factors associated with type 2 diabetes and cardiovascular disease: data from the National Health and Nutrition Examination Survey 1999-2006.","volume":"8","author":"DeBoer","year":"2010","journal-title":"Metab Syndr Relat Disord"},{"issue":"4","key":"zoi240636r38","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1586\/14779072.2016.1143360","article-title":"A metabolic syndrome severity score to estimate risk in adolescents and adults: current evidence and future potential.","volume":"14","author":"Lee","year":"2016","journal-title":"Expert Rev Cardiovasc Ther"},{"issue":"6","key":"zoi240636r39","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1111\/jhn.v35.6","article-title":"Characterising body composition and bone health in transgender individuals receiving gender-affirming hormone therapy.","volume":"35","author":"Ford","year":"2022","journal-title":"J Hum Nutr Diet"},{"issue":"10","key":"zoi240636r40","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.2337\/diacare.46.10.1579","article-title":"Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat.","volume":"46","author":"Goodpaster","year":"1997","journal-title":"Diabetes"},{"issue":"1","key":"zoi240636r41","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1080\/08964289.2019.1644283","article-title":"Clinical complexity in women veterans: a systematic review of the recent evidence on mental health and physical health comorbidities.","volume":"47","author":"Creech","year":"2021","journal-title":"Behav Med"},{"issue":"6","key":"zoi240636r42","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1001\/jamacardio.2021.0227","article-title":"Association of posttraumatic stress disorder and incident ischemic heart disease in women veterans.","volume":"6","author":"Ebrahimi","year":"2021","journal-title":"JAMA Cardiol"},{"issue":"5 Pt 2","key":"zoi240636r43","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1111\/hesr.2005.40.issue-5p2","article-title":"Measurement in Veterans Affairs health services research: veterans as a special population.","volume":"40","author":"Morgan","year":"2005","journal-title":"Health Serv Res"},{"key":"zoi240636r44","doi-asserted-by":"publisher","DOI":"10.1017\/S2045796024000118","article-title":"Mental health impact of multiple sexually minoritized and gender expansive stressors among LGBTQ+ young adults: a latent class analysis.","volume":"33","author":"Shrader","year":"2024","journal-title":"Epidemiol Psychiatr Sci"},{"key":"zoi240636r3"},{"key":"zoi240636r26","author":"VA Information Resource Center","year":"2015"},{"key":"zoi240636r34"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2820670\/hashemi_2024_oi_240636_1719332760.55741.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T11:41:36Z","timestamp":1719920496000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2820670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,2]]},"references-count":44,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.19696","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,2]]}}}