{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T09:10:23Z","timestamp":1784106623137,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"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":["Andrology"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Traditionally, Klinefelter syndrome (KS) was considered a clinical condition associated with hyperestrogenism.<\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n To compare circulating sex steroids, particularly estrogens, in a cohort of KS and non\u2010KS hypogonadal men.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n A cohort of hypogonadal men, treated and untreated, was prospectively enrolled in a real\u2010life study at the Endocrinology of Modena. In our clinical lab, serum total testosterone (TT) and estradiol (E2) were assayed twice by two different methods on the same serum sample: immunoassay (IA) with the CMIA D\u00d7I800 system (Beckman Coulter) and liquid chromatography\u2013tandem mass spectrometry (LC\u2010MS\/MS) with the Chromsystems MassChrom Steroids. Sex hormone binding globulin (SHBG) was measured by IA for the calculated free testosterone (cFT) by the Vermeulen formula. Results are expressed as median and interquartile ranges in parentheses.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Note that 203 men (117 KS and 86 non\u2010KS) were included. Age [KS 32.69 (20.62\u201341.92); non\u2010KS 46.62 (34.30\u201362.52)], body mass index [KS 24.72 (21.93\u201330.70); non\u2010KS 28.41 (24.34\u201331.83) were lower in KS than non\u2010KS (\n p<\/jats:italic>\n < 0.001). KS were significantly taller (1.80, 1.74\u20131.84\u00a0vs. 1.77, 1.69\u20131.79,\n p<\/jats:italic>\n < 0.001), while weight (82.90, 69.00\u2013100.25\u00a0vs. 83.00, 73.00\u2013100.00,\n p<\/jats:italic>\n = 0.149) did not differ.\n <\/jats:p>\n \n Gonadotropins were higher in KS (\n p<\/jats:italic>\n < 0.001). TT, cFT, E2, and SHBG did not differ between KS and non\u2010KS, both using IA and LC\/MS\u2010MS (\n p<\/jats:italic>\n > 0.05). E2 and E2\/TT did not differ between the two groups, irrespective of the assay used.\n <\/jats:p>\n \n A significant positive correlation was observed between TT concentrations measured by either IA or LC\u2010MS\/MS, in both KS (\n R<\/jats:italic>\n 2<\/jats:sup>\n = 0.647,\n p<\/jats:italic>\n < 0.001) and non\u2010KS (\n R<\/jats:italic>\n 2<\/jats:sup>\n = 0.820, < 0.001), even when analyzing the correlation between total or calculated free T and E2 measured by LC\u2010MS\/MS in both groups (TT:\n R<\/jats:italic>\n 2<\/jats:sup>\n = 0.102,\n p<\/jats:italic>\n = 0.001\u00a0vs.\n R<\/jats:italic>\n 2<\/jats:sup>\n = 0.219,\n p<\/jats:italic>\n < 0.001; cFT:\n R<\/jats:italic>\n 2<\/jats:sup>\n = 0.162,\n p<\/jats:italic>\n < 0.001 vs.\n R<\/jats:italic>\n 2<\/jats:sup>\n = 0.235,\n p<\/jats:italic>\n < 0.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Serum E2 and E2\/TT did not differ between KS and non\u2010KS along the entire spectrum of TT values (from low to normal\/high) within the normal range, suggesting no difference in aromatization of estrogen in KS patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/andr.70310","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T08:51:49Z","timestamp":1784105509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex Steroids Measurement by Mass Spectrometry in Hypogonadal Men in a\n Real\u2010World<\/i>\n Setting: Serum Estradiol (E2) and E2 to Total Testosterone Ratio Do Not Differ Between Patients With Klinefelter Syndrome and Non\u2010Klinefelter Syndrome Hypogonadism"],"prefix":"10.1111","author":[{"given":"Daniele Renda","family":"Livraghi","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6946-6172","authenticated-orcid":false,"given":"Francesco","family":"Costantino","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy"},{"name":"Department of Medical Specialties Unit of Endocrinology, Azienda Ospedaliero\u2010Universitaria di Modena, Ospedale Civile di Baggiovara Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Vignali","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Canu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Azienda USL of Modena Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"De Santis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Azienda USL of Modena Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Roli","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Azienda USL of Modena Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Fasano","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Azienda USL of Modena Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8169-0696","authenticated-orcid":false,"given":"Vincenzo","family":"Rochira","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy"},{"name":"Department of Medical Specialties Unit of Endocrinology, Azienda Ospedaliero\u2010Universitaria di Modena, Ospedale Civile di Baggiovara Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-5683","authenticated-orcid":false,"given":"Sara","family":"De Vincentis","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy"},{"name":"Department of Medical Specialties Unit of Endocrinology, Azienda Ospedaliero\u2010Universitaria di Modena, Ospedale Civile di Baggiovara Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"issue":"9430","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0140-6736(04)16678-6","article-title":"Klinefelter's Syndrome","volume":"364","author":"Lanfranco 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A.","year":"2013","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"1","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/andr.12909","article-title":"European Academy of Andrology Guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology","volume":"9","author":"Zitzmann M.","year":"2021","journal-title":"Andrology"},{"issue":"2","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s40618-016-0541-6","article-title":"Klinefelter Syndrome (KS): Genetics, Clinical Phenotype and Hypogonadism","volume":"40","author":"Bonomi M.","year":"2017","journal-title":"Journal of Endocrinological Investigation"},{"issue":"11","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1210\/jcem-2-11-615","article-title":"Syndrome Characterized by Gynecomastia, Aspermatogenesis Without A\u2010Leydigism, and Increased Excretion of Follicle\u2010Stimulating Hormone 1","volume":"2","author":"Klinefelter H. 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L.","year":"1970","journal-title":"Acta Endocrinologica"},{"issue":"4","key":"e_1_2_11_13_1","first-page":"737","article-title":"Biosynthesis of Testosterone and Oestrogens In Vitro by the Testicular Tissue From Patients With Klinefelter's Syndrome","volume":"66","author":"Sharma D. C.","year":"1971","journal-title":"Acta Endocrinologica"},{"issue":"2","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1210\/jc.2006-1864","article-title":"Utility, Limitations, and Pitfalls in Measuring Testosterone: An Endocrine Society Position Statement","volume":"92","author":"Rosner W.","year":"2007","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"key":"e_1_2_11_15_1","volume-title":"Endotext","author":"Rochira V.","year":"2000"},{"key":"e_1_2_11_16_1","first-page":"1","volume-title":"Endocrinology of the Testis and Male Reproduction","author":"Rochira V.","year":"2017"},{"issue":"10","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1210\/jc.2013-3375","article-title":"Requirement for Mass Spectrometry Sex Steroid Assays in the Journal of Clinical Endocrinology and Metabolism","volume":"98","author":"Handelsman D. J.","year":"2013","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"5","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.beem.2013.05.015","article-title":"Novel Liquid Chromatography Tandem Mass Spectrometry (LC\u2010MS\/MS) Methods for Measuring Steroids","volume":"27","author":"Keevil B. G.","year":"2013","journal-title":"Best Practice & Research Clinical Endocrinology & Metabolism"},{"issue":"2","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s12020-019-01850-y","article-title":"Relative Hyperestrogenism in Klinefelter Syndrome: Results From a Meta\u2010analysis","volume":"64","author":"Santi D.","year":"2019","journal-title":"Endocrine"},{"issue":"3","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"E508","DOI":"10.1210\/jc.2014-2834","article-title":"Anthropometry in Klinefelter Syndrome \u2013 Multifactorial Influences Due to CAG Length, Testosterone Treatment and Possibly Intrauterine Hypogonadism","volume":"100","author":"Chang S.","year":"2015","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"2","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa0911101","article-title":"Identification of Late\u2010onset Hypogonadism in Middle\u2010aged and Elderly Men","volume":"363","author":"Wu F. C. W.","year":"2010","journal-title":"New England Journal of Medicine"},{"issue":"2","key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa2215025","article-title":"Cardiovascular Safety of Testosterone\u2010Replacement Therapy","volume":"389","author":"Lincoff A. M.","year":"2023","journal-title":"New England Journal of Medicine"},{"issue":"7","key":"e_1_2_11_23_1","first-page":"613","article-title":"Mediation Analysis of the Testosterone Treatment Effect to Prevent Type 2 Diabetes in the Testosterone for Prevention of Type 2 Diabetes Mellitus Trial","volume":"188","author":"Robledo K. 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R.","year":"1983","journal-title":"Journal of Clinical Endocrinology & Metabolism"},{"issue":"6","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/BF01626608","article-title":"Bone Mass and Mineral Metabolism in Klinefelter's Syndrome","volume":"5","author":"Luisetto G.","year":"1995","journal-title":"Osteoporosis International"},{"key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/978-3-319-44441-3_16","volume-title":"Endocrinology of the Testis and Male Reproduction","author":"Pagotto U.","year":"2017"}],"container-title":["Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/andr.70310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/andr.70310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T08:51:53Z","timestamp":1784105513000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/andr.70310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":29,"alternative-id":["10.1111\/andr.70310"],"URL":"https:\/\/doi.org\/10.1111\/andr.70310","archive":["Portico"],"relation":{},"ISSN":["2047-2919","2047-2927"],"issn-type":[{"value":"2047-2919","type":"print"},{"value":"2047-2927","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"assertion":[{"value":"2026-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"andr.70310"}}