{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:06:28Z","timestamp":1789686388279,"version":"4.0.1"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Testosterone treatment is a necessary component of care for some transgender and gender-diverse individuals. Observational studies have reported associations between commencement of gender-affirming hormone therapy and improvements in gender dysphoria and depression, but there is a lack of data from randomized clinical trials.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess the effect of testosterone therapy compared with no treatment on gender dysphoria, depression, and suicidality in transgender and gender-diverse adults seeking masculinization.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>A 3-month open-label randomized clinical trial was conducted at endocrinology outpatient clinics and primary care clinics specializing in transgender and gender-diverse health in Melbourne, Australia, from November 1, 2021, to July 22, 2022. Participants included transgender and gender-diverse adults aged 18 to 70 years seeking initiation of testosterone therapy.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Immediate initiation of testosterone commencement (intervention group) or no treatment (standard care waiting list of 3 months before commencement). This design ensured no individuals would be waiting longer than the time to standard care.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was gender dysphoria, as measured by the Gender Preoccupation and Stability Questionnaire. Secondary outcomes included the Patient Health Questionnaire-9 (PHQ-9) to assess depression and the Suicidal Ideation Attributes Scale (SIDAS) to assess suicidality. Questionnaires were undertaken at 0 and 3 months. The evaluable cohort was analyzed.<\/jats:p><\/jats:sec>Results<\/jats:title>Sixty-four transgender and gender-diverse adults (median [IQR] age, 22.5 [20-27] years) were randomized. Compared with standard care, the intervention group had a decrease in gender dysphoria (mean difference, \u22127.2 points; 95% CI, \u22128.3 to \u22126.1 points; P<\/jats:italic>\u2009&amp;lt;\u2009.001), a clinically significant decrease in depression (ie, change in score of 5 points on PHQ-9; mean difference, \u22125.6 points; 95% CI, \u22126.8 to \u22124.4 points; P<\/jats:italic>\u2009&amp;lt;\u2009.001), and a significant decrease in suicidality (mean difference in SIDAS score, \u22126.5 points; 95% CI, \u22128.2 to \u22124.8 points; P<\/jats:italic>\u2009&amp;lt;\u2009.001). Resolution of suicidality assessed by PHQ-9 item 9 occurred in 11 individuals (52%) with immediate testosterone commencement compared with 1 (5%) receiving standard care (P<\/jats:italic>\u2009=\u2009.002). Seven individuals reported injection site pain\/discomfort and 1 individual reported a transient headache 24 hours following intramuscular administration of testosterone undecanoate. No individual developed polycythemia.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this open-label randomized clinical trial of testosterone therapy in transgender and gender-diverse adults, immediate testosterone compared with no treatment significantly reduced gender dysphoria, depression, and suicidality in transgender and gender-diverse individuals desiring testosterone therapy.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ANZCTR Identifier: ACTRN1262100016864<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.31919","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T15:32:46Z","timestamp":1694100766000},"page":"e2331919","source":"Crossref","is-referenced-by-count":70,"title":["Early Access to Testosterone Therapy in Transgender and Gender-Diverse Adults Seeking Masculinization"],"prefix":"10.1001","volume":"6","author":[{"given":"Brendan 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