{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:13:20Z","timestamp":1790630000120,"version":"4.1.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ALF agreement","award":["ALFGBG 990637"],"award-info":[{"award-number":["ALFGBG 990637"]}]},{"name":"Rigshospitalet\u2019s Research Council"},{"DOI":"10.13039\/501100004836","name":"Independent Research Fund Denmark","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009777","name":"Region Halland","doi-asserted-by":"publisher","award":["932841"],"award-info":[{"award-number":["932841"]}],"id":[{"id":"10.13039\/501100009777","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vera and Hans Albrechtsson Foundation"},{"DOI":"10.13039\/501100005689","name":"Gothenburg Medical Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005689","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Increased height is a characteristic of Klinefelter syndrome (KS). Detailed evaluation of growth patterns in boys and adolescents carrying a 47,XXY karyotype is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To delineate detailed growth patterns during the different growth phases and their contribution to the increased adult height in boys with KS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Longitudinal data on growth from 55 boys with KS were compared with a reference from the GrowUp1974Gothenburg cohort using a statistical growth model using 4 mathematical functions: the QEPS model. A subgroup of 35 boys out of whom 34 were on testosterone replacement therapy (TRT) reached final height.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The infant growth period was shorter with a lower height gain (Emax, 63.3 vs 65.1\u2005cm, P &amp;lt; .001) in boys with KS. The boys gained more height during the childhood growth phase, (Qmax, 110.9 vs 104.1\u2005cm, P &amp;lt; .001), and onset of pubertal growth was earlier as compared with the reference (11.3 vs 11.8 years, P &amp;lt; .001). The total pubertal height gain was higher (32.9 vs 30.6\u2005cm, P &amp;lt; .001) due to more basic growth; the specific pubertal growth was equal, resulting in a taller adult height (184.6 vs 180.5\u2005cm, P &amp;lt; .001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The boys with KS exhibited a different growth pattern as compared with a healthy reference population, with less and shorter growth in infant life and more basic growth during childhood and the pubertal years (the Q-function growth by the QEPS model), resulting in taller adult height.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jendso\/bvaf206","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T13:14:40Z","timestamp":1765372480000},"source":"Crossref","is-referenced-by-count":3,"title":["Age-specific Contributions to Height in Boys with Klinefelter Syndrome: Analysis of Growth Using the QEPS Model"],"prefix":"10.1210","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-8726","authenticated-orcid":false,"given":"Anton","family":"Holmgren","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , 41685 Gothenburg ,","place":["Sweden"]},{"name":"Department of Pediatrics, Halland Hospital , 30185 Halmstad ,","place":["Sweden"]},{"name":"Department of Research and Development, Region Halland , Box 517, 301 80 Halmstad ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimon","family":"Niklasson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , 41685 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Gelander","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , 41685 Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas F M","family":"Nierop","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , 41685 Gothenburg ,","place":["Sweden"]},{"name":"Muvara bv, Multivariate Analysis of Research Data , 2353 PH Leiderdorp ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldina","family":"Pivodic","sequence":"additional","affiliation":[{"name":"APNC , Entrepren\u00f6rsstr\u00e5ket 10, 431 53 M\u00f6lndal ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0534-4350","authenticated-orcid":false,"given":"Anders","family":"Juul","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital\u2014Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Copenhagen University Hospital\u2014Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7885-7467","authenticated-orcid":false,"given":"Lise","family":"Aksglaede","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital\u2014Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Copenhagen University Hospital\u2014Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"issue":"2","key":"2026020606114600000_bvaf206-B1","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 and Metab"},{"issue":"11","key":"2026020606114600000_bvaf206-B2","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1210\/jcem-2-11-615","article-title":"Clinical syndrome characterized by gynecomastia, aspermatogenesis, without A-leydigism and increased excretion of follicle stimulating hormone","volume":"2","author":"Klinefelter","year":"1942","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2026020606114600000_bvaf206-B3","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1210\/jc.2004-1424","article-title":"X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients","volume":"89","author":"Zitzmann","year":"2004","journal-title":"J Clin Endocrinol and Metab"},{"issue":"1","key":"2026020606114600000_bvaf206-B4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1210\/jc.2007-1426","article-title":"Abnormal sex chromosome constitution and longitudinal growth: serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with 47,XXY, 47,XYY, or sex-determining region of the Y chromosome","volume":"93","author":"Aksglaede","year":"2008","journal-title":"J Clin Endocrinol and Metab"},{"issue":"5","key":"2026020606114600000_bvaf206-B5","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/ajmg.a.33334","article-title":"Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy","volume":"152","author":"Ottesen","year":"2010","journal-title":"Am J Med Genet A"},{"issue":"6pt2","key":"2026020606114600000_bvaf206-B6","doi-asserted-by":"crossref","first-page":"e642","DOI":"10.1111\/j.1365-2605.2011.01223.x","article-title":"Genotype and phenotype in Klinefelter syndrome\u2014impact of androgen receptor polymorphism and skewed X inactivation","volume":"34","author":"Bojesen","year":"2011","journal-title":"Int J Androl"},{"issue":"6","key":"2026020606114600000_bvaf206-B7","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/j.1365-2265.2007.02977.x","article-title":"Establishment of testicular endocrine function impairment during childhood and puberty in boys with Klinefelter syndrome","volume":"67","author":"Bastida","year":"2007","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"5","key":"2026020606114600000_bvaf206-B8","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.jpeds.2007.10.019","article-title":"Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome","volume":"152","author":"Zeger","year":"2008","journal-title":"J Pediatr"},{"issue":"6","key":"2026020606114600000_bvaf206-B9","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/j.1651-2227.2011.02161.x","article-title":"Insulin resistance and metabolic syndrome in prepubertal boys with Klinefelter syndrome","volume":"100","author":"Bardsley","year":"2011","journal-title":"Acta Paediatr"},{"issue":"6","key":"2026020606114600000_bvaf206-B10","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1111\/andr.12249","article-title":"Testicular function during puberty and young adulthood in patients with Klinefelter's syndrome with and without spermatozoa in seminal fluid","volume":"4","author":"Rohayem","year":"2016","journal-title":"Andrology"},{"issue":"6","key":"2026020606114600000_bvaf206-B11","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/j.1651-2227.2011.02246.x","article-title":"Clinical and biological parameters in 166 boys, adolescents and adults with nonmosaic Klinefelter syndrome: a Copenhagen experience","volume":"100","author":"Aksgl\u00e6de","year":"2011","journal-title":"Acta Paediatr"},{"issue":"4","key":"2026020606114600000_bvaf206-B12","first-page":"1","article-title":"Edinburgh study of growth and development of children with sex chromosome abnormalities IV","volume":"26","author":"Ratcliffe","year":"1990","journal-title":"Birth Defects Orig Artic Ser"},{"issue":"2","key":"2026020606114600000_bvaf206-B13","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1136\/adc.80.2.192","article-title":"Long-term outcome in children of sex chromosome abnormalities","volume":"80","author":"Ratcliffe","year":"1999","journal-title":"Arch Dis Child"},{"issue":"1","key":"2026020606114600000_bvaf206-B14","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13023-018-0976-2","article-title":"Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study 11 medical and health sciences 1117 public health and health services","volume":"14","author":"Berglund","year":"2019","journal-title":"Orphanet J Rare Dis"},{"issue":"2","key":"2026020606114600000_bvaf206-B15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/apa.16162","article-title":"The quadratic-exponential-pubertal-stop model is valid for analysing human growth patterns and developing novel growth references","volume":"111","author":"Holmgren","year":"2022","journal-title":"Acta Paediatr"},{"key":"2026020606114600000_bvaf206-B16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jtbi.2016.06.007","article-title":"Modelling individual longitudinal human growth from fetal to adult life\u2014QEPS I","volume":"406","author":"Nierop","year":"2016","journal-title":"J Theor Biol"},{"issue":"1","key":"2026020606114600000_bvaf206-B17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12887-017-0857-1","article-title":"Insight into human pubertal growth by applying the QEPS growth model","volume":"17","author":"Holmgren","year":"2017","journal-title":"BMC Pediatr"},{"issue":"9","key":"2026020606114600000_bvaf206-B18","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1515\/jpem-2020-0127","article-title":"A new type of pubertal height reference based on growth aligned for onset of pubertal growth","volume":"33","author":"Albertsson-Wikland","year":"2020","journal-title":"J Pediatr Endocrinol and Metab"},{"issue":"1","key":"2026020606114600000_bvaf206-B19","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s12887-022-03304-3","article-title":"Novel type of references for BMI aligned for onset of puberty\u2014using the QEPS growth model","volume":"22","author":"Albertsson-Wikland","year":"2022","journal-title":"BMC Pediatr"},{"issue":"1","key":"2026020606114600000_bvaf206-B20","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41390-020-01234-3","article-title":"The pubertal growth spurt is diminished in children with severe obesity","volume":"90","author":"Holmgren","year":"2021","journal-title":"Pediatr Res"},{"issue":"4","key":"2026020606114600000_bvaf206-B21","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1111\/apa.15129","article-title":"A new Swedish reference for total and prepubertal height","volume":"109","author":"Albertsson-Wikland","year":"2020","journal-title":"Acta Paediatr"},{"issue":"1","key":"2026020606114600000_bvaf206-B22","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1186\/s12887-021-02954-z","article-title":"Novel type of references for weight aligned for onset of puberty\u2014using the QEPS growth model","volume":"21","author":"Albertsson-Wikland","year":"2021","journal-title":"BMC Pediatr"},{"issue":"1","key":"2026020606114600000_bvaf206-B23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41390-018-0014-z","article-title":"Estimating secular changes in longitudinal growth patterns underlying adult height with the QEPS model: the Grow Up Gothenburg cohorts","volume":"84","author":"Holmgren","year":"2018","journal-title":"Pediatr Res"},{"issue":"3","key":"2026020606114600000_bvaf206-B24","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/pr.2016.253","article-title":"Pubertal height gain is inversely related to peak BMI in childhood","volume":"81","author":"Holmgren","year":"2017","journal-title":"Pediatr Res"},{"issue":"7","key":"2026020606114600000_bvaf206-B25","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1651-2227.2002.tb03322.x","article-title":"Swedish population-based longitudinal reference values from birth to 18 years of age for height, weight and head circumference","volume":"91","author":"Wikland","year":"2002","journal-title":"Acta Paediatr"},{"key":"2026020606114600000_bvaf206-B26","doi-asserted-by":"crossref","unstructured":"Holmgren A, Niklasson A, Gelander L, et al \u00a0Supplemental Table 1 for \u201cAge-specific Contributions to Height in Boys with Klinefelter Syndrome: Analysis of Growth Using the QEPS Model\u201d. Figshare. 2025. Deposited 4 November 2025. 10.6084\/m9.figshare.30535730.v1","DOI":"10.1210\/jendso\/bvaf206"},{"issue":"7","key":"2026020606114600000_bvaf206-B27","first-page":"e230031","article-title":"Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome","volume":"12","author":"Krabbe","year":"2023","journal-title":"Endocr Connect"},{"issue":"1","key":"2026020606114600000_bvaf206-B28","first-page":"39","article-title":"Early androgen deficiency in infants and young boys with 47,XXY Klinefelter syndrome","volume":"64","author":"Ross","year":"2005","journal-title":"Horm Res"},{"issue":"6","key":"2026020606114600000_bvaf206-B29","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1111\/j.1651-2227.2011.02280.x","article-title":"Clinical and hormonal status of infants with nonmosaic XXY karyotype","volume":"100","author":"Lahlou","year":"2011","journal-title":"Acta Paediatr"},{"key":"2026020606114600000_bvaf206-B30","first-page":"243","article-title":"The Edinburgh study of growth and development in children with sex chromosome abnormalities","volume":"15","author":"Ratcliffe","year":"1979","journal-title":"Birth Defects Orig Artic Ser"},{"issue":"3","key":"2026020606114600000_bvaf206-B31","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1136\/archdischild-2020-320831","article-title":"Klinefelter syndrome: going beyond the diagnosis","volume":"108","author":"Butler","year":"2023","journal-title":"Arch Dis Child"},{"issue":"1","key":"2026020606114600000_bvaf206-B32","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/andr.12909","article-title":"European academy of andrology guidelines on Klinefelter syndrome","volume":"9","author":"Zitzmann","year":"2021","journal-title":"Andrology"},{"issue":"jan30 1","key":"2026020606114600000_bvaf206-B33","doi-asserted-by":"crossref","first-page":"f518","DOI":"10.1136\/bmj.f518","article-title":"Klinefelter's syndrome does not cause delayed puberty","volume":"346","author":"Butler","year":"2013","journal-title":"BMJ"},{"issue":"1","key":"2026020606114600000_bvaf206-B34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s40618-020-01281-x","article-title":"From mini-puberty to pre-puberty: early impairment of the hypothalamus\u2013pituitary\u2013gonadal axis with normal testicular function in children with non-mosaic Klinefelter syndrome","volume":"44","author":"Spaziani","year":"2021","journal-title":"J Endocrinol Invest"},{"issue":"3","key":"2026020606114600000_bvaf206-B35","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/cen.14588","article-title":"Onset and progression of puberty in Klinefelter syndrome","volume":"96","author":"Tanner","year":"2022","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"7","key":"2026020606114600000_bvaf206-B36","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1111\/apa.14683","article-title":"Nordic populations are still getting taller\u2014secular changes in height from the 20th to 21st century","volume":"108","author":"Holmgren","year":"2019","journal-title":"Acta Paediatr"},{"issue":"2","key":"2026020606114600000_bvaf206-B37","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/apa.12468","article-title":"The 2014 Danish references from birth to 20 years for height, weight and body mass index","volume":"103","author":"Tinggaard","year":"2014","journal-title":"Acta Paediatr"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/jendso\/bvaf206\/65849628\/bvaf206.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/10\/3\/bvaf206\/65849628\/bvaf206.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/10\/3\/bvaf206\/65849628\/bvaf206.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T11:11:57Z","timestamp":1770376317000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/doi\/10.1210\/jendso\/bvaf206\/8377697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,2,6]]}},"URL":"https:\/\/doi.org\/10.1210\/jendso\/bvaf206","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2025,12,12]]},"article-number":"bvaf206"}}