{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:34:57Z","timestamp":1791905697438,"version":"4.3.4"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Surgery GFT Research Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Testosterone deficiency (TD), or male hypogonadism, affects up to 25% of Canadian men aged 40 to 60. Testosterone replacement therapy (TRT) is widely used to manage symptoms of TD. Despite over seven decades of clinical use, the relationship between TRT and major adverse cardiovascular events (MACE) remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the association between TRT and MACE using a large population-based database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A propensity-weighted, retrospective cohort study was conducted using provincial health administrative databases. Men were eligible if they had no prior TRT use or MACE and maintained at least one year of provincial health coverage between April 1, 1995, and December 31, 2018. TRT was defined as having at least two prescriptions filled within one year for testosterone products (capsules, gels, patches, or injections). MACE was defined as the first occurrence of myocardial infarction, coronary revascularization, ischemic stroke, or hospitalization for heart failure. A logistic regression model including age, socioeconomic status, index year, diabetes, hypertension, dyslipidemia, and renal disease generated propensity scores. Stabilized inverse propensity treatment weighting was applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>A Cox proportional hazards model was used to assess time to first MACE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 6949 men who received TRT and 415\u2009837 controls, TRT was associated with a 27% increased risk of MACE (HR 1.27, 95% CI: 1.16-1.39) in weighted analyses. Among 7306 men diagnosed with TD and 442\u2009602 matched controls, those with TD also showed a 27% increased risk of MACE (HR 1.27, 95% CI: 1.16-1.39). Median time to MACE was 2828\u00a0days in the TRT group and 2707\u00a0days in controls. MACE occurred in 9.95% of TRT users versus 5.56% of controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Implications<\/jats:title>\n                    <jats:p>Clinicians should be aware that both TRT and underlying TD are associated with increased cardiovascular risk. Assessment of comorbidities and patient-specific cardiovascular risk remains essential when initiating TRT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Strengths &amp; Limitations<\/jats:title>\n                    <jats:p>This study leverages a large, real-world, population-based dataset with robust propensity weighting methodology. However, unmeasured confounding such as obesity, smoking, or physical activity levels may influence outcomes. Diagnostic coding limitations may also affect TD case identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both TRT use and TD were associated with a significantly increased risk of MACE. Whether TRT independently drives this risk or merely reflects underlying disease requires further investigation. Risk stratification and shared decision-making should guide the initiation of TRT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdaf306","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:13:16Z","timestamp":1760011996000},"source":"Crossref","is-referenced-by-count":2,"title":["Association between testosterone replacement therapy and cardiovascular events in men: a retrospective propensity-weighted analysis"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-7535","authenticated-orcid":false,"given":"Dhiraj S","family":"Bal","sequence":"first","affiliation":[{"name":"Max Rady College of Medicine, University of Manitoba , Winnipeg, MB , R3E 0T4,","place":["Canada"]},{"name":"Department of Surgery, University of Manitoba , Winnipeg, MB , R3A 1R9,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian G","family":"Fidel","sequence":"additional","affiliation":[{"name":"Max Rady College of Medicine, University of Manitoba , Winnipeg, MB , R3E 0T4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapilan","family":"Panchendrabose","sequence":"additional","affiliation":[{"name":"Max Rady College of Medicine, University of Manitoba , Winnipeg, MB , R3E 0T4,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uday","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Manitoba , Winnipeg, MB , R3A 1R9,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranveer","family":"Brar","sequence":"additional","affiliation":[{"name":"Chronic Disease Innovation Center , Winnipeg, MB , R2V 4W1,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Premal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Manitoba , Winnipeg, MB , R3A 1R9,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"issue":"9","key":"2026010506141238800_ref1","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.jsxm.2018.06.012","article-title":"Endogenous testosterone levels and cardiovascular risk: meta-analysis of observational studies","volume":"15","author":"Corona","year":"2018","journal-title":"J Sex Med"},{"issue":"5","key":"2026010506141238800_ref2","doi-asserted-by":"publisher","first-page":"E234","DOI":"10.5489\/cuaj.7252","article-title":"Canadian Urological Association clinical practice guideline on testosterone deficiency in men: evidence-based Q&A","volume":"15","author":"Grober","year":"2021","journal-title":"Can Urol Assoc J"},{"issue":"11","key":"2026010506141238800_ref3","doi-asserted-by":"publisher","first-page":"e015284","DOI":"10.1136\/bmjopen-2016-015284","article-title":"Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis","volume":"7","author":"Elliott","year":"2017","journal-title":"BMJ Open"},{"issue":"11","key":"2026010506141238800_ref4","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1001\/jama.2019.9290","article-title":"Testosterone deficiency","volume":"322","author":"Halpern","year":"2019","journal-title":"JAMA."},{"issue":"17","key":"2026010506141238800_ref5","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1001\/jama.2013.280386","article-title":"Association of Testosterone Therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels","volume":"310","author":"Vigen","year":"2013","journal-title":"JAMA."},{"issue":"2","key":"2026010506141238800_ref6","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1056\/NEJMoa1000485","article-title":"Adverse events associated with testosterone administration","volume":"363","author":"Basaria","year":"2010","journal-title":"N Engl J Med"},{"issue":"1","key":"2026010506141238800_ref7","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/1741-7015-11-108","article-title":"Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials","volume":"11","author":"Xu","year":"2013","journal-title":"BMC Med"},{"issue":"6","key":"2026010506141238800_ref8","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1210\/jc.2011-2591","article-title":"Testosterone treatment and mortality in men with low testosterone levels","volume":"97","author":"Shores","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2026010506141238800_ref9","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1517\/14740338.2014.950653","article-title":"Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis","volume":"13","author":"Corona","year":"2014","journal-title":"Expert Opin Drug Saf"},{"issue":"2","key":"2026010506141238800_ref10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1056\/NEJMoa2215025","article-title":"Cardiovascular safety of testosterone-replacement therapy","volume":"389","author":"Lincoff","year":"2023","journal-title":"N Engl J Med"},{"issue":"20","key":"2026010506141238800_ref11","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1161\/CIRCULATIONAHA.117.029652","article-title":"Socioeconomic status and cardiovascular outcomes: challenges and interventions","volume":"137","author":"Schultz","year":"2018","journal-title":"Circulation."},{"issue":"2","key":"2026010506141238800_ref12","doi-asserted-by":"publisher","first-page":"183","DOI":"10.21037\/tau.2016.11.16","article-title":"Testosterone deficiency in adults and corresponding treatment patterns across the globe","volume":"6","author":"Anaissie","year":"2017","journal-title":"Transl Androl Urol"},{"issue":"9","key":"2026010506141238800_ref13","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1177\/1060028014539918","article-title":"Risk of myocardial infarction in older men receiving testosterone therapy","volume":"48","author":"Baillargeon","year":"2014","journal-title":"Ann Pharmacother"},{"issue":"4","key":"2026010506141238800_ref14","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1001\/jamainternmed.2016.9546","article-title":"Association of Testosterone Replacement with cardiovascular outcomes among men with androgen deficiency","volume":"177","author":"Cheetham","year":"2017","journal-title":"JAMA Intern Med"},{"issue":"3","key":"2026010506141238800_ref15","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1530\/EJE-09-0092","article-title":"Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men","volume":"161","author":"Mathur","year":"2009","journal-title":"Eur J Endocrinol"},{"issue":"6","key":"2026010506141238800_ref16","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/S2213-8587(16)00112-1","article-title":"Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study","volume":"4","author":"Wallis","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026010506141238800_ref17","doi-asserted-by":"publisher","first-page":"970750","DOI":"10.1155\/2015\/970750","article-title":"Myocardial infarction and stroke risk in young healthy men treated with injectable testosterone","volume":"2015","author":"Tan","year":"2015","journal-title":"Int J Endocrinol"},{"issue":"17","key":"2026010506141238800_ref18","doi-asserted-by":"publisher","first-page":"e020562","DOI":"10.1161\/JAHA.120.020562","article-title":"Association between testosterone treatment and risk of incident cardiovascular events among US male veterans with low testosterone levels and multiple medical comorbidities","volume":"10","author":"Shores","year":"2021","journal-title":"J Am Heart Assoc"},{"issue":"6","key":"2026010506141238800_ref19","doi-asserted-by":"publisher","first-page":"e381","DOI":"10.1016\/S2666-7568(22)00096-4","article-title":"Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis","volume":"3","author":"Hudson","year":"2022","journal-title":"Lancet Healthy Longev"},{"key":"2026010506141238800_ref20","doi-asserted-by":"publisher","first-page":"1182113","DOI":"10.3389\/fphar.2023.1182113","article-title":"Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database","volume":"14","author":"Zhao","year":"2023","journal-title":"Front Pharmacol"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/23\/1\/qdaf306\/65044287\/qdaf306.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/23\/1\/qdaf306\/65044287\/qdaf306.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:14:18Z","timestamp":1767611658000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/doi\/10.1093\/jsxmed\/qdaf306\/8307082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/jsxmed\/qdaf306","relation":{},"ISSN":["1743-6095","1743-6109"],"issn-type":[{"value":"1743-6095","type":"print"},{"value":"1743-6109","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,10,31]]},"article-number":"qdaf306"}}