{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T05:44:06Z","timestamp":1781329446902,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"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"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Klinefelter syndrome (KS) is a common sex chromosome aneuploidy affecting one to two per 1000 live male births. Testosterone therapy and neuropsychological support can enhance the quality of life in affected individuals. While cognitive deficits have been documented in Klinefelter syndrome, the influence of hormonal variability on cognitive profiles remains underexplored. This study aimed to determine whether testosterone levels correlate with neurocognitive functions in Klinefelter syndrome individuals. This cross\u2010sectional study involved a heterogeneous clinical sample from a single tertiary referral hospital. Participants: Thirty Klinefelter syndrome individuals were enrolled, being 21 with 47,\u00a0XXY without neurological comorbidities, aged 17\u201365 years. Participants underwent blood tests for total testosterone, free testosterone, estradiol, sex\u2010hormone\u2010binding globulin, follicle\u2010stimulating hormone, luteinizing hormone, and anti\u2010M\u00fcllerian hormone. A comprehensive neuropsychological assessment was also conducted, covering intellectual quotient (Wechsler Scale) and higher\u2010order cognitive functions (attention, executive functions, language, memory, and visuoconstructional abilities). Neuropsychological performance was notably better in Klinefelter syndrome individuals with higher levels of testosterone. Spearman's test revealed significant correlations between total testosterone, free testosterone, and gonadal status measured by free testosterone\/luteinizing hormone and free testosterone\/estradiol ratios and cognitive flexibility tasks. The mean age of participants was 33.1 years (SD\u00a0=\u00a014.0), and free testosterone\/luteinizing hormone and free testosterone\/estradiol measures were correlated with set\u2010shifting, verbal memory, visual functions, and adaptive behavior domains, including communication, daily living, and motor skills. The free testosterone:estradiol ratio was also consistently associated with total intellectual quotient, verbal comprehension, perceptual organization, and processing speed indexes. The study highlights the positive correlation between testosterone levels and cognitive functions in Klinefelter syndrome males. These insights reinforce the role of testosterone in neurocognitive development, suggesting the potential benefits of testosterone therapy in managing cognitive deficits in Klinefelter syndrome. More extensive confirmatory studies are necessary to substantiate these findings and to explore the mechanisms involved.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70002","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T02:22:49Z","timestamp":1737944569000},"page":"2216-2226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Higher testosterone level is associated with improved cognitive functions in Klinefelter syndrome"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-2293","authenticated-orcid":false,"given":"Luciane","family":"Simonetti","sequence":"first","affiliation":[{"name":"Adolescent\u2010to\u2010Adult Transition Endocrinology Clinic Hospital S\u00e3o Paulo Division of Endocrinology Department of Medicine Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo (EPM\u2010Unifesp)  S\u00e3o Paulo SP Brazil"},{"name":"Laboratory of Molecular and Translational Endocrinology Division of Endocrinology Division of Endocrinology and Metabolism Department of Medicine Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-6900","authenticated-orcid":false,"given":"Lucas G. 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