{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:42:37Z","timestamp":1791567757987,"version":"4.3.4"},"reference-count":106,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Klinefelter syndrome (KS), most commonly arises from a 47,XXY karyotype. While KS affects around 1 in 450 to 600 male births, an estimated 50% to 75% of cases go undiagnosed. Individuals with KS are at increased risk of metabolic, cardiovascular, and reproductive comorbidities, increasing mortality risk, psychological burden, and significantly diminished health-related quality of life (HR-QoL) compared to healthy controls. We provide an updated review of the recent literature on the clinical management for people with KS, associated comorbidities, and the implications on HR-QoL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Acquisition<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted of key databases MEDLINE, CINAHL, Cochrane, Psychinfo, and EMBASE, followed by a gray search of relevant key papers in KS with medical guideline organizations being searched online and, where available, their publications and proposed guidelines being assessed. All databases were searched from their inception until December 2024, and English-language restrictions applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Synthesis<\/jats:title>\n                    <jats:p>Current evidence highlights the need for early detection, the importance of appropriate medication management, and multidisciplinary care to address infertility, cancer risks, neurocognitive deficits, and adverse mental health. Lifespan-specific interventions remain underexplored, necessitating further research to optimize outcomes and refine clinical guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>KS management is guided by only one endorsed guideline. International and interprofessional collaboration is needed to develop consensus documents. Existing guidelines pay minimal attention to the numerous HR-QoL challenges, overlooking the effect and diagnosis of psychological comorbidities. Enhancing HR-QoL and optimizing physical and mental well-being should be prioritized to improve HR-QoL outcomes in people with KS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf261","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T08:11:35Z","timestamp":1745914295000},"page":"e2435-e2445","source":"Crossref","is-referenced-by-count":13,"title":["Update on Physical, Psychological, and Quality of Life Management in Klinefelter Syndrome"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9049-4283","authenticated-orcid":false,"given":"Brien","family":"Mehmet","sequence":"first","affiliation":[{"name":"School of Health & Medical Sciences, City St George's, University of London, Northampton Square , London EC1V 0HB ,","place":["UK"]},{"name":"Department of Endocrinology and Diabetes, Royal Free Hospital NHS Foundation Trust , London NW3 2QG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7023-6794","authenticated-orcid":false,"given":"Andrew A","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Endocrinology, Diabetes, and Metabolism Service, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]},{"name":"Harvard Reproductive Endocrine Sciences Center and Reproductive Endocrine Unit , Massachusetts General Hospital, Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2578-8223","authenticated-orcid":false,"given":"Channa N","family":"Jayasena","sequence":"additional","affiliation":[{"name":"Department of Investigative Medicine, Imperial College London , Hammersmith, London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9686-2232","authenticated-orcid":false,"given":"Steve","family":"Gillard","sequence":"additional","affiliation":[{"name":"School of Health & Medical Sciences, City St George's, University of London, Northampton Square , London EC1V 0HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3606-5370","authenticated-orcid":false,"given":"Sofia","family":"Llahana","sequence":"additional","affiliation":[{"name":"School of Health & Medical Sciences, City St George's, University of London, Northampton Square , London EC1V 0HB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"issue":"2","key":"2025071507131697500_dgaf261-B1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.fertnstert.2012.06.019","article-title":"The genetic origin of Klinefelter syndrome and its effect on spermatogenesis","volume":"98","author":"Maiburg","year":"2012","journal-title":"Fertil Steril"},{"issue":"1","key":"2025071507131697500_dgaf261-B2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5694\/j.1326-5377.2011.tb04141.x","article-title":"The prevalence and diagnosis rates of Klinefelter syndrome: an Australian comparison","volume":"194","author":"Herlihy","year":"2011","journal-title":"Med J Aust"},{"issue":"2","key":"2025071507131697500_dgaf261-B3","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1210\/jc.2002-021491","article-title":"Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study","volume":"88","author":"Bojesen","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025071507131697500_dgaf261-B4","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1210\/er.2017-00212","article-title":"Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology","volume":"39","author":"Gravholt","year":"2018","journal-title":"Endocr Rev"},{"issue":"3","key":"2025071507131697500_dgaf261-B5","first-page":"73","article-title":"Edinburgh study of growth and development of children with sex chromosome abnormalities. 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