{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T03:59:27Z","timestamp":1781236767219,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Klinefelter syndrome (KS), defined by a 47, XXY karyotype, is commonly associated with progressive testicular failure. The precise timing of Sertoli and Leydig cell dysfunction during puberty remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the onset and progression of testicular insufficiency during puberty in KS, and to assess whether diagnostic timing (prenatal vs postnatal) impacts pubertal phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective, single\u2010centre study of 57 patients with KS aged 9\u201325 years, followed from the prepubertal period at Lille University Hospital. Longitudinal clinical and hormonal data were analysed according to pubertal stage rather than chronological age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients entered puberty spontaneously at a physiological age (mean 12.6 years), but experienced a slow pubertal tempo (mean duration: 4.08 years). Sertoli cell dysfunction appeared within 12 months of pubertal onset, with rising FSH and declining AMH and inhibin B levels. Inhibin B concentrations never reached the reference range for Tanner stage 5 and declined below the adult threshold (92\u2009pg\/mL) 2 years after pubertal onset. Leydig cell dysfunction, defined by elevated LH and low\u2010normal testosterone, emerged after 36 months. At puberty completion, 94% had Sertoli cell insufficiency (i.e. FSH level &gt;\u20097.19 IU\/L) and 80% had Leydig cell insufficiency (LH\u2009&gt;\u20095.88 IU\/L). Postnatally diagnosed patients exhibited significantly higher LH (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) and lower inhibin B (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Testicular insufficiency in KS begins approximately 18 months after pubertal onset, with Sertoli cell failure preceding Leydig cell decline. Early diagnosis and longitudinal monitoring are essential to guide endocrine management and to support individualized counselling regarding fertility preservation strategies, which should be considered according to pubertal stage rather than chronological age.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.70159","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T03:36:06Z","timestamp":1781235366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pubertal Dynamics of Sertoli and Leydig Cell Dysfunction in Klinefelter Syndrome"],"prefix":"10.1111","author":[{"given":"Tredez","family":"Axelle","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, DevGen, Reference Centre for Genital Development Abnormalities, CHU Lille University of Lille Lille 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Endocrinology, DevGen, Reference Centre for Genital Development Abnormalities, CHU Lille University of Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Marcelli","sequence":"additional","affiliation":[{"name":"Department of Andrology, Urology and Renal Transplantation University of Lille, CHU Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Laure","family":"Barbotin","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology\u2010Spermiology\u2010CECOS University of Lille, CHU Lille Lille France"},{"name":"University of Lille, CHU\u2010Lille, Inserm U1172, Lille Neuroscience &amp; Cognition Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Pigny","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Hormonology, Metabolism\u2013Nutrition and Oncology Unit, CHU\u2010Lille University of Lille Lille France"},{"name":"U1277\u2010CANTHER\u2010Cancer\u2010Heterogeneity Plasticity and Resistance to Therapies, Inserm, CHU Lille University of Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0443-8344","authenticated-orcid":false,"given":"Hamza","family":"Benderradji","sequence":"additional","affiliation":[{"name":"Department of Andrology, Urology and Renal Transplantation University of Lille, CHU Lille Lille France"},{"name":"University of Lille, CHU\u2010Lille, Inserm U1172, Lille Neuroscience &amp; Cognition Lille France"},{"name":"Department of Endocrinology, Diabetology, and Metabolism University of Lille, CHU Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Leroy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, DevGen, Reference Centre for Genital Development Abnormalities, CHU Lille University of Lille Lille France"},{"name":"Department of Andrology, Urology and Renal Transplantation University of Lille, CHU Lille Lille 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