{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:45:40Z","timestamp":1792788340953,"version":"4.5.0"},"reference-count":35,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005747","name":"A.P. Moller Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015223","name":"Danish Diabetes and Endocrine Academy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015223","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF22SA0079901"],"award-info":[{"award-number":["NNF22SA0079901"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF15OC0016474"],"award-info":[{"award-number":["NNF15OC0016474"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF20OC0060610"],"award-info":[{"award-number":["NNF20OC0060610"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011958","name":"Independent Research Fund Denmark","doi-asserted-by":"publisher","award":["2096-00165A"],"award-info":[{"award-number":["2096-00165A"]}],"id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sygesikringen Danmark","award":["2022-0189"],"award-info":[{"award-number":["2022-0189"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Klinefelter syndrome (KS) is underdiagnosed, undertreated, and associated with metabolic dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We compared incidences of metabolic disorders among men with KS, either undiagnosed (U-KS), diagnosed and untreated (D-KS), or treated with testosterone replacement therapy (T-KS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a national Danish registry-based study from January 1994 to December 2022. We computed hazard ratios (HR) for incidence and severity of metabolic disorders between risk set matched strata of U-KS, D-KS, and T-KS and male control individuals. We evaluated the effect of parenteral vs transdermal testosterone supplementation on incidence of metabolic disorders in T-KS, applying inverse probability weighting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 508 age-matched strata of U-KS, D-KS, and T-KS, and included 46 241 male controls. Incidence of metabolic conditions was more than 2-fold increased in KS, including type 2 diabetes (HR 2.56 [1.85-3.44]). U-KS presented with the most severe metabolic phenotype, with more obesity and more late-stage diabetes complications compared with T-KS (HR 2.83 [1.33-6.02]). All-cause mortality following diagnosis of type 2 diabetes was increased in D-KS compared with controls (HR 1.77 [1.28-2.45]), but nondifferential for T-KS and controls (HR 1.30 [0.68-2.48]). We saw a pattern of less obesity and type 2 diabetes, but more hypertension and hypercholesterolemia, with parenteral vs transdermal testosterone supplementation in T-KS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The metabolic profile in men with KS is dependent on diagnosis and treatment status, with pronounced metabolic dysfunction in U-KS. Better diagnosis and treatment of KS are needed to alleviate metabolic dysfunction and improve survival in men with KS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf619","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:55:30Z","timestamp":1762865730000},"page":"1311-1318","source":"Crossref","is-referenced-by-count":6,"title":["Metabolism and Type 2 Diabetes Across Life Stages in Klinefelter Syndrome: A Population-Based Cohort Study"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1130-3659","authenticated-orcid":false,"given":"Simon","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Aarhus University Hospital , DK-8200 Aarhus N ,","place":["Denmark"]},{"name":"Department of Molecular Medicine, Aarhus University Hospital , DK-8200 Aarhus N 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