{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:13:18Z","timestamp":1790629998956,"version":"4.1.0"},"reference-count":58,"publisher":"Bioscientifica","issue":"7","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,3]]},"abstract":"<jats:p>Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9\u201320.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters.<\/jats:p>","DOI":"10.1530\/ec-23-0031","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T07:17:24Z","timestamp":1680506244000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":9,"title":["Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome"],"prefix":"10.1530","volume":"12","author":[{"given":"Hans Valdemar","family":"L\u00f3pez Krabbe","sequence":"first","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen","family":"Holm Petersen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"},{"name":"Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise Laub","family":"Asserh\u00f8j","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Fertility, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine Holm","family":"Johannsen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke Beck","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line Hartvig","family":"Cleemann","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper P","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e6rke","family":"Priskorn","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina M","family":"Main","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0534-4350","authenticated-orcid":true,"given":"Anders","family":"Juul","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7885-7467","authenticated-orcid":true,"given":"Lise","family":"Aksglaede","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Endocrine Reviews","first-page":"389","article-title":"Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology","volume":"39","author":"Gravholt","year":"2018","unstructured":"Gravholt CHChang SWallentin MFedder JMoore P & Skakkeb\u00e6k A. Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology. Endocrine Reviews201839389\u2013423. (https:\/\/doi.org\/10.1210\/er.2017-00212)"},{"key":"bib2","series-title":"Clinical Endocrinology","first-page":"276","article-title":"Primary testicular failure in Klinefelter\u2019s syndrome: the use of bivariate luteinizing hormone-testosterone reference charts","volume":"66","author":"Aksglaede","year":"2007","unstructured":"Aksglaede LAndersson AMJ\u00f8rgensen NJensen TKCarlsen EMcLachlan RISkakkeb\u00e6k NEPetersen JH & Juul A. Primary testicular failure in Klinefelter\u2019s syndrome: the use of bivariate luteinizing hormone-testosterone reference charts. Clinical Endocrinology200766276\u2013281. (https:\/\/doi.org\/10.1111\/j.1365-2265.2006.02722.x)"},{"key":"bib3","series-title":"Journal of Endocrinological Investigation","first-page":"1769","article-title":"First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy","volume":"45","author":"Pasquali","year":"2022","unstructured":"Pasquali DChiodini PSimeon VFerlin AVignozzi LCorona GLanfranco FRochira VCalogero AEBonomi M, et al. First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy. Journal of Endocrinological Investigation2022451769\u20131776. (https:\/\/doi.org\/10.1007\/s40618-022-01816-4)"},{"key":"bib4","series-title":"Lancet","first-page":"273","article-title":"Klinefelter\u2019s syndrome","volume":"364","author":"Lanfranco","year":"2004","unstructured":"Lanfranco FKamischke AZitzmann M & Nieschlag E. Klinefelter\u2019s syndrome. Lancet2004364273\u2013283. (https:\/\/doi.org\/10.1016\/S0140-6736(0416678-6)"},{"key":"bib5","series-title":"Molecular Reproduction and Development","first-page":"17","article-title":"Global transcriptome analysis of peripheral blood identifies the most significantly down-regulated genes associated with metabolism regulation in Klinefelter syndrome","volume":"82","author":"Huang","year":"2015","unstructured":"Huang JZhang LDeng HChang LLiu Q & Liu P. Global transcriptome analysis of peripheral blood identifies the most significantly down-regulated genes associated with metabolism regulation in Klinefelter syndrome. Molecular Reproduction and Development20158217\u201325. (https:\/\/doi.org\/10.1002\/mrd.22438)"},{"key":"bib6","series-title":"Human Molecular Genetics","first-page":"1219","article-title":"Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity","volume":"26","author":"Belling","year":"2017","unstructured":"Belling KRusso FJensen ABDalgaard MDWestergaard DRajpert-De Meyts ESkakkeb\u00e6k NEJuul A & Brunak S. Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity. Human Molecular Genetics2017261219\u20131229. (https:\/\/doi.org\/10.1093\/hmg\/ddx014)"},{"key":"bib7","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"E518","article-title":"Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome","volume":"100","author":"Zitzmann","year":"2015","unstructured":"Zitzmann MBongers RWerler SBogdanova NWistuba JKliesch SGromoll J & T\u00fcttelmann F. Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome. Journal of Clinical Endocrinology and Metabolism2015100E518\u2013E523. (https:\/\/doi.org\/10.1210\/jc.2014-2780)"},{"key":"bib8","series-title":"Journal of the Endocrine Society","first-page":"2276","article-title":"Testosterone treatment in infants with 47,XXY: effects on body composition","volume":"3","author":"Davis","year":"2019","unstructured":"Davis SMReynolds RMDabelea DMZeitler PS & Tartaglia NR. Testosterone treatment in infants with 47,XXY: effects on body composition. Journal of the Endocrine Society201932276\u20132285 . (https:\/\/doi.org\/10.1210\/js.2019-00274)"},{"key":"bib9","series-title":"Andrology","first-page":"1169","article-title":"Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome","volume":"4","author":"Davis","year":"2016","unstructured":"Davis SLahlou NBardsley MTemple MCKowal KPyle LZeitler P & Ross J. Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome. Andrology201641169\u20131177. (https:\/\/doi.org\/10.1111\/andr.12275)"},{"key":"bib10","series-title":"Acta Paediatrica","first-page":"866","article-title":"Insulin resistance and metabolic syndrome in prepubertal boys with Klinefelter syndrome","volume":"100","author":"Bardsley","year":"2011","unstructured":"Bardsley MZFalkner BKowal K & Ross JL. Insulin resistance and metabolic syndrome in prepubertal boys with Klinefelter syndrome. Acta Paediatrica2011100866\u2013870. (https:\/\/doi.org\/10.1111\/j.1651-2227.2011.02161.x)"},{"key":"bib11","series-title":"Archives of Disease in Childhood","first-page":"30","article-title":"Normal bone mineral content but unfavourable muscle\/fat ratio in Klinefelter syndrome","volume":"93","author":"Aksglaede","year":"2008","unstructured":"Aksglaede LMolgaard CSkakkeb\u00e6k NE & Juul A. Normal bone mineral content but unfavourable muscle\/fat ratio in Klinefelter syndrome. Archives of Disease in Childhood20089330\u201334. (https:\/\/doi.org\/10.1136\/adc.2007.120675)"},{"key":"bib12","series-title":"Journal of the Endocrine Society","first-page":"bvab016","article-title":"Cortical bone mass is low in boys with Klinefelter syndrome and improves with oxandrolone","volume":"5","author":"Vogiatzi","year":"2021","unstructured":"Vogiatzi MGDavis SM & Ross JL. Cortical bone mass is low in boys with Klinefelter syndrome and improves with oxandrolone. Journal of the Endocrine Society20215bvab016. (https:\/\/doi.org\/10.1210\/jendso\/bvab016)"},{"key":"bib13","series-title":"International Journal of Endocrinology","first-page":"3032759","article-title":"Bone mineral status in children and adolescents with Klinefelter syndrome","volume":"2016","author":"Stagi","year":"2016","unstructured":"Stagi SDi MManoni CScalini PChiarelli FVerrotti ALapi EGiglio SDosa L & Martino De M. Bone mineral status in children and adolescents with Klinefelter syndrome. International Journal of Endocrinology201620163032759 . (https:\/\/doi.org\/10.1155\/2016\/3032759)"},{"key":"bib14","series-title":"Lancet","first-page":"1264","article-title":"Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries","volume":"363","author":"Boisen","year":"2004","unstructured":"Boisen KAKaleva MMain KMVirtanen HEHaavisto AMSchmidt IMChellakooty MDamgaard INMau CReunanen M, et al. Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet20043631264\u20131269. (https:\/\/doi.org\/10.1016\/S0140-6736(0415998-9)"},{"key":"bib15","series-title":"European Journal of Clinical Nutrition","first-page":"664","article-title":"Body fat throughout childhood in 2647 healthy Danish children: agreement of BMI, waist circumference, skinfolds with dual X-ray absorptiometry","volume":"68","author":"Wohlfahrt-Veje","year":"2014","unstructured":"Wohlfahrt-Veje CTinggaard JWinther KMouritsen AHagen CPMieritz MGRenzy-Martin De KTBoas MPetersen JH & Main KM. Body fat throughout childhood in 2647 healthy Danish children: agreement of BMI, waist circumference, skinfolds with dual X-ray absorptiometry. European Journal of Clinical Nutrition201468664\u2013670. (https:\/\/doi.org\/10.1038\/ejcn.2013.282)"},{"key":"bib16","series-title":"Human Reproduction","first-page":"998","article-title":"Average sperm count remains unchanged despite reduction in maternal smoking: results from a large cross-sectional study with annual investigations over 21 years","volume":"33","author":"Priskorn","year":"2018","unstructured":"Priskorn LNordkap LBang AKKrause MHolmboe SAEgeberg Palme DLWinge SBM\u00f8rup NCarlsen EJoensen UN, et al. Average sperm count remains unchanged despite reduction in maternal smoking: results from a large cross-sectional study with annual investigations over 21 years. Human Reproduction201833998\u20131008. (https:\/\/doi.org\/10.1093\/humrep\/dey090)"},{"key":"bib17","series-title":"Clinica Chimica Acta; International Journal of Clinical Chemistry","first-page":"6","article-title":"Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17\u03b1-hydroxyprogesterone, \u03b44-androstenedione, testosterone and their ratios in children, adolescents and young adults","volume":"437","author":"S\u00f8eborg","year":"2014","unstructured":"S\u00f8eborg TFrederiksen HMouritsen AJohannsen THMain KMJ\u00f8rgensen NPetersen JHAndersson AM & Juul A. Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17\u03b1-hydroxyprogesterone, \u03b44-androstenedione, testosterone and their ratios in children, adolescents and young adults. Clinica Chimica Acta; International Journal of Clinical Chemistry20144376\u201313. (https:\/\/doi.org\/10.1016\/j.cca.2014.06.018)"},{"key":"bib18","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"754","article-title":"Sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by LC-MS\/MS","volume":"105","author":"Frederiksen","year":"2020","unstructured":"Frederiksen HJohannsen THAndersen SEAlbrethsen JLandersoe SKPetersen JHAndersen ANVestergaard ETSchorring MELinneberg A, et al. Sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by LC-MS\/MS. Journal of Clinical Endocrinology and Metabolism2020105754\u2013768. (https:\/\/doi.org\/10.1210\/clinem\/dgz196)"},{"key":"bib19","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"3666","article-title":"A critical evaluation of simple methods for the estimation of free testosterone in serum","volume":"84","author":"Vermeulen","year":"1999","unstructured":"Vermeulen AVerdonck L & Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. Journal of Clinical Endocrinology and Metabolism1999843666\u20133672. (https:\/\/doi.org\/10.1210\/jcem.84.10.6079)"},{"key":"bib20","series-title":"Steroids","first-page":"512","article-title":"A novel spreadsheet method for calculating the free serum concentrations of testosterone, dihydrotestosterone, estradiol, estrone and cortisol: with illustrative examples from male and female populations","volume":"74","author":"Mazer","year":"2009","unstructured":"Mazer NA. A novel spreadsheet method for calculating the free serum concentrations of testosterone, dihydrotestosterone, estradiol, estrone and cortisol: with illustrative examples from male and female populations. Steroids200974512\u2013519. (https:\/\/doi.org\/10.1016\/j.steroids.2009.01.008)"},{"key":"bib21","series-title":"Human Reproduction","first-page":"2323","article-title":"The LH\/FSH ratio is not a sex-dimorphic marker after infancy: data from 6417 healthy individuals and 125 patients with Differences of Sex Development","volume":"35","author":"Ljubicic","year":"2020","unstructured":"Ljubicic MLJespersen KAksglaede LHagen CPPetersen JHAndersen HRLinneberg AMain KMAndersson AMJohannsen TH, et al. The LH\/FSH ratio is not a sex-dimorphic marker after infancy: data from 6417 healthy individuals and 125 patients with Differences of Sex Development. Human Reproduction2020352323\u20132335. (https:\/\/doi.org\/10.1093\/humrep\/deaa182)"},{"key":"bib22","series-title":"Archives of Disease in Childhood","first-page":"13","article-title":"Variations in the pattern of pubertal changes in boys","volume":"45","author":"Marshall","year":"1970","unstructured":"Marshall WA & Tanner JM. Variations in the pattern of pubertal changes in boys. Archives of Disease in Childhood19704513\u201323. (https:\/\/doi.org\/10.1136\/adc.45.239.13)"},{"key":"bib23","series-title":"Acta Paediatrica","first-page":"214","article-title":"The 2014 Danish references from birth to 20 years for height, weight and body mass index","volume":"103","author":"Tinggaard","year":"2014","unstructured":"Tinggaard JAksglaede LS\u00f8rensen KMouritsen AWohlfahrt-Veje CHagen CPMieritz MGJ\u00f8rgensen NWolthers ODHeuck C, et al. The 2014 Danish references from birth to 20 years for height, weight and body mass index. Acta Paediatrica2014103214\u2013224. (https:\/\/doi.org\/10.1111\/apa.12468)"},{"key":"bib24","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"5357","article-title":"Changes in anti-M\u00fcllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years","volume":"95","author":"Aksglaede","year":"2010","unstructured":"Aksglaede LS\u00f8rensen KBoas MMouritsen AHagen CPJensen RBPetersen JHLinneberg AAndersson AMMain KM, et al. Changes in anti-M\u00fcllerian hormone (AMH) throughout the life span: a population-based study of 1027 healthy males from birth (cord blood) to the age of 69 years. Journal of Clinical Endocrinology and Metabolism2010955357\u20135364. (https:\/\/doi.org\/10.1210\/jc.2010-1207)"},{"key":"bib25","series-title":"European Journal of Endocrinology","first-page":"P1","article-title":"Peptide hormone analysis in diagnosis and treatment of differences of sex development: joint position paper of EU cost action \u2018SDnet\u2019 and European reference network on rare endocrine conditions","volume":"182","author":"Johannsen","year":"2020","unstructured":"Johannsen THAndersson AMAhmed SFRijke De YBGreaves RFHartmann MFHiort OHolterhus PMKrone NPKulle A, et al. Peptide hormone analysis in diagnosis and treatment of differences of sex development: joint position paper of EU cost action \u2018SDnet\u2019 and European reference network on rare endocrine conditions. European Journal of Endocrinology2020182P1\u2013P15. (https:\/\/doi.org\/10.1530\/EJE-19-0831)"},{"key":"bib26","series-title":"Journal of Endocrinological Investigation","first-page":"297","article-title":"Body composition, trabecular bone score and vertebral fractures in subjects with Klinefelter syndrome","volume":"46","author":"Vena","year":"2023","unstructured":"Vena WCarrone FDelbarba AAkpojiyovbi OPezzaioli LCFacondo PCappelli CLeonardi LBalzarini LFarina D, et al. Body composition, trabecular bone score and vertebral fractures in subjects with Klinefelter syndrome. Journal of Endocrinological Investigation202346297\u2013304 . (https:\/\/doi.org\/10.1007\/s40618-022-01901-8)"},{"key":"bib27","series-title":"Diabetes Care","first-page":"1591","article-title":"The metabolic syndrome is frequent in Klinefelter\u2019s syndrome and is associated with abdominal obesity and hypogonadism","volume":"29","author":"Bojesen","year":"2006","unstructured":"Bojesen AKristensen KBirkebaek NHFedder JMosekilde LBennett PLaurberg PFrystyk JFlyvbjerg AChristiansen JS, et al. The metabolic syndrome is frequent in Klinefelter\u2019s syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care2006291591\u20131598. (https:\/\/doi.org\/10.2337\/dc06-0145)"},{"key":"bib28","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1254","article-title":"Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses","volume":"91","author":"Bojesen","year":"2006","unstructured":"Bojesen AJuul SBirkeb\u00e6k NH & Gravholt CH. Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. Journal of Clinical Endocrinology and Metabolism2006911254\u20131260. (https:\/\/doi.org\/10.1210\/jc.2005-0697)"},{"key":"bib29","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"6516","article-title":"Mortality in patients with Klinefelter syndrome in Britain: a cohort study","volume":"90","author":"Swerdlow","year":"2005","unstructured":"Swerdlow AJHiggins CDSchoemaker MJWright AFJacobs PA & United Kingdom ClinicalCytogenetics Group. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. Journal of Clinical Endocrinology and Metabolism2005906516\u20136522. (https:\/\/doi.org\/10.1210\/jc.2005-1077)"},{"key":"bib30","series-title":"American Journal of Medical Genetics. Part C, Seminars in Medical Genetics","first-page":"327","article-title":"High prevalence of cardiometabolic risk features in adolescents with 47,XXY\/Klinefelter syndrome","volume":"184","author":"Davis","year":"2020","unstructured":"Davis SMDeKlotz SNadeau KJKelsey MMZeitler PS & Tartaglia NR. High prevalence of cardiometabolic risk features in adolescents with 47,XXY\/Klinefelter syndrome. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics2020184327\u2013333. (https:\/\/doi.org\/10.1002\/ajmg.c.31784)"},{"key":"bib31","series-title":"Archives of Pediatrics and Adolescent Medicine","first-page":"826","article-title":"Effect of android to gynoid fat ratio on insulin resistance in obese youth","volume":"163","author":"Aucouturier","year":"2009","unstructured":"Aucouturier JMeyer MThivel DTaillardat M & Duch\u00e9 P. Effect of android to gynoid fat ratio on insulin resistance in obese youth. Archives of Pediatrics and Adolescent Medicine2009163826\u2013831. (https:\/\/doi.org\/10.1001\/archpediatrics.2009.148)"},{"key":"bib32","series-title":"Diabetic Medicine","first-page":"174","article-title":"Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment","volume":"37","author":"Gianatti","year":"2020","unstructured":"Gianatti EJ & Grossmann M. Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment. Diabetic Medicine202037174\u2013186. (https:\/\/doi.org\/10.1111\/dme.13977)"},{"key":"bib33","series-title":"Acta Paediatrica","first-page":"793","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","unstructured":"Aksgl\u00e6de LSkakkeb\u00e6k NEAlmstrup K & Juul A. Clinical and biological parameters in 166 boys, adolescents and adults with nonmosaic Klinefelter syndrome: A Copenhagen experience. Acta Paediatrica2011100793\u2013806. (https:\/\/doi.org\/10.1111\/j.1651-2227.2011.02246.x)"},{"key":"bib34","series-title":"Journal of Endocrinological Investigation","first-page":"1675","article-title":"Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis","volume":"43","author":"Pizzocaro","year":"2020","unstructured":"Pizzocaro AVena WCondorelli RRadicioni ARastrelli GPasquali DSelice RFerlin AForesta CJannini EA, et al. Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis. Journal of Endocrinological Investigation2020431675\u20131687. (https:\/\/doi.org\/10.1007\/s40618-020-01299-1)"},{"key":"bib35","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"176","article-title":"Effects of oxandrolone on cardiometabolic health in boys with Klinefelter syndrome: a randomized controlled trial","volume":"102","author":"Davis","year":"2017","unstructured":"Davis SMCox-Martin MGBardsley MZKowal KZeitler PS & Ross JL. Effects of oxandrolone on cardiometabolic health in boys with Klinefelter syndrome: a randomized controlled trial. Journal of Clinical Endocrinology and Metabolism2017102176\u2013184. (https:\/\/doi.org\/10.1210\/jc.2016-2904)"},{"key":"bib36","series-title":"Journal of Endocrinological Investigation","first-page":"967","article-title":"Testosterone supplementation and body composition: results from a meta-analysis of observational studies","volume":"39","author":"Corona","year":"2016","unstructured":"Corona GGiagulli VAMaseroli EVignozzi LAversa AZitzmann MSaad FMannucci E & Maggi M. Testosterone supplementation and body composition: results from a meta-analysis of observational studies. Journal of Endocrinological Investigation201639967\u2013981. (https:\/\/doi.org\/10.1007\/s40618-016-0480-2)"},{"key":"bib37","series-title":"Journal of Bone and Mineral Research","first-page":"2474","article-title":"Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in Klinefelter syndrome","volume":"29","author":"Shanbhogue","year":"2014","unstructured":"Shanbhogue VVHansen SJ\u00f8rgensen NRBrixen K & Gravholt CH. Bone geometry, volumetric density, microarchitecture, and estimated bone strength assessed by HR-pQCT in Klinefelter syndrome. Journal of Bone and Mineral Research2014292474\u20132482. (https:\/\/doi.org\/10.1002\/jbmr.2272)"},{"key":"bib38","series-title":"Calcified Tissue International","first-page":"35","article-title":"Klinefelter bone microarchitecture evolution with testosterone replacement therapy","volume":"111","author":"Piot","year":"2022","unstructured":"Piot APlotton IBoutroy SBacchetta JAilloud SLejeune HChapurlat RDSzulc P & Confavreux CB. Klinefelter bone microarchitecture evolution with testosterone replacement therapy. Calcified Tissue International202211135\u201346. (https:\/\/doi.org\/10.1007\/s00223-022-00956-2)"},{"key":"bib39","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"E739","article-title":"Bone mass in subjects with Klinefelter syndrome: role of testosterone levels and androgen receptor gene cag polymorphism","volume":"96","author":"Ferlin","year":"2011","unstructured":"Ferlin ASchipilliti MVinanzi CGarolla AMambro Di ASelice RLenzi A & Foresta C. Bone mass in subjects with Klinefelter syndrome: role of testosterone levels and androgen receptor gene cag polymorphism. Journal of Clinical Endocrinology and Metabolism201196E739\u2013E745. (https:\/\/doi.org\/10.1210\/jc.2010-1878)"},{"key":"bib40","series-title":"Andrology","first-page":"1699","article-title":"Prevalence and determinants of radiological vertebral fractures in patients with Klinefelter syndrome","volume":"8","author":"Vena","year":"2020","unstructured":"Vena WPizzocaro AIndirli RAmer MMaffezzoni FDelbarba ALeonardi LBalzarini LUlivieri FMFerlin A, et al. Prevalence and determinants of radiological vertebral fractures in patients with Klinefelter syndrome. Andrology202081699\u20131704. (https:\/\/doi.org\/10.1111\/andr.12841)"},{"key":"bib41","series-title":"Osteoporosis International","first-page":"1441","article-title":"Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone","volume":"22","author":"Bojesen","year":"2011","unstructured":"Bojesen ABirkeb\u00e6k NKristensen KHeickendorff LMosekilde LChristiansen JS & Gravholt CH. Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone. Osteoporosis International2011221441\u20131450. (https:\/\/doi.org\/10.1007\/s00198-010-1354-7)"},{"key":"bib42","series-title":"Endocrine","first-page":"327","article-title":"Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter syndrome","volume":"61","author":"Tahani","year":"2018","unstructured":"Tahani NNieddu LProssomariti GSpaziani MGranato SCarlomagno FAnzuini ALenzi ARadicioni AF & Romagnoli E. Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter syndrome. Endocrine201861327\u2013335. (https:\/\/doi.org\/10.1007\/s12020-018-1604-6)"},{"key":"bib43","series-title":"Osteoporosis International","first-page":"1281","article-title":"The National Osteoporosis Foundation\u2019s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations","volume":"27","author":"Weaver","year":"2016","unstructured":"Weaver CMGordon CMJanz KFKalkwarf HJLappe JMLewis RO\u2019Karma MWallace TC & Zemel BS. The National Osteoporosis Foundation\u2019s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporosis International2016271281\u20131386. (https:\/\/doi.org\/10.1007\/s00198-015-3440-3)"},{"key":"bib44","series-title":"Archives of Disease in Childhood","first-page":"10","article-title":"Whole body bone mineral accretion in healthy children and adolescents","volume":"81","author":"M\u00f8lgaard","year":"1999","unstructured":"M\u00f8lgaard CThomsen BL & Michaelsen KF. Whole body bone mineral accretion in healthy children and adolescents. Archives of Disease in Childhood19998110\u201315. (https:\/\/doi.org\/10.1136\/adc.81.1.10)"},{"key":"bib45","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"169","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 (SRY)-positive 46,XX karyotypes","volume":"93","author":"Aksglaede","year":"2008","unstructured":"Aksglaede LSkakkebaek NE & Juul A. 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 (SRY)-positive 46,XX karyotypes. Journal of Clinical Endocrinology and Metabolism200893169\u2013176. (https:\/\/doi.org\/10.1210\/jc.2007-1426)"},{"key":"bib46","series-title":"Andrology","first-page":"145","article-title":"European academy of andrology guidelines on Klinefelter syndrome Endorsing Organization: European Society of Endocrinology","volume":"9","author":"Zitzmann","year":"2021","unstructured":"Zitzmann MAksglaede LCorona GIsidori AMJuul AT\u2019Sjoen GKliesch SD\u2019Hauwers KToppari JS\u0142owikowska-Hilczer J, et al. European academy of andrology guidelines on Klinefelter syndrome Endorsing Organization: European Society of Endocrinology. Andrology20219145\u2013167. (https:\/\/doi.org\/10.1111\/andr.12909)"},{"key":"bib47","series-title":"Endocrine Reviews","article-title":"Androgens during infancy, childhood, and adolescence: physiology and use in clinical practice","volume":"41","author":"Mason","year":"2020","unstructured":"Mason KASchoelwer MJ & Rogol AD. Androgens during infancy, childhood, and adolescence: physiology and use in clinical practice. Endocrine Reviews202041. (https:\/\/doi.org\/10.1210\/endrev\/bnaa003)"},{"key":"bib48","series-title":"European Journal of Endocrinology","first-page":"G9","article-title":"Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline","volume":"186","author":"Nordenstr\u00f6m","year":"2022","unstructured":"Nordenstr\u00f6m AAhmed SFAkker van den EBlair JBonomi MBrachet CBroersen LHAClaahsen-Van der Grinten HLDessens ABGawlik A, et al. Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline. European Journal of Endocrinology2022186G9\u2013G49. (https:\/\/doi.org\/10.1530\/EJE-22-0073)"},{"key":"bib49","series-title":"Journal of Adolescent Health","first-page":"20","article-title":"A multicenter, open-label, observational study of testosterone gel (1%) in the treatment of adolescent boys with Klinefelter syndrome or anorchia","volume":"54","author":"Rogol","year":"2014","unstructured":"Rogol ADSwerdloff RSReiter EORoss JLZumbrunnen TLPratt GABrennan JJBenesh JKan-Dobrosky N & Miller MG. A multicenter, open-label, observational study of testosterone gel (1%) in the treatment of adolescent boys with Klinefelter syndrome or anorchia. Journal of Adolescent Health20145420\u201325. (https:\/\/doi.org\/10.1016\/j.jadohealth.2013.07.021)"},{"issue":"Supplement","key":"bib50","series-title":"Journal of Urology","first-page":"1527","article-title":"Safety and efficacy of testosterone replacement therapy in adolescents with Klinefelter syndrome","volume":"191","author":"Mehta","year":"2014","unstructured":"Mehta AClearman T & Paduch DA. Safety and efficacy of testosterone replacement therapy in adolescents with Klinefelter syndrome. Journal of Urology2014191(Supplement) 1527\u20131531. (https:\/\/doi.org\/10.1016\/j.juro.2013.09.015)"},{"key":"bib51","series-title":"Andrology","first-page":"1178","article-title":"Testicular function during puberty and young adulthood in patients with Klinefelter\u2019s syndrome with and without spermatozoa in seminal fluid","volume":"4","author":"Rohayem","year":"2016","unstructured":"Rohayem JNieschlag EZitzmann M & Kliesch S. Testicular function during puberty and young adulthood in patients with Klinefelter\u2019s syndrome with and without spermatozoa in seminal fluid. Andrology201641178\u20131186. (https:\/\/doi.org\/10.1111\/andr.12249)"},{"key":"bib52","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1376","article-title":"Evaluation of 451 Danish boys with delayed puberty: diagnostic use of a new puberty nomogram and effects of oral testosterone therapy","volume":"100","author":"Lawaetz","year":"2015","unstructured":"Lawaetz JGHagen CPMieritz MGJensen MBPetersen JH & Juul A. Evaluation of 451 Danish boys with delayed puberty: diagnostic use of a new puberty nomogram and effects of oral testosterone therapy. Journal of Clinical Endocrinology and Metabolism20151001376\u20131385. (https:\/\/doi.org\/10.1210\/jc.2014-3631)"},{"key":"bib53","series-title":"American Journal of Medical Genetics. Part C, Seminars in Medical Genetics","first-page":"302","article-title":"Gonadal dysfunction and beyond: clinical challenges in children, adolescents, and adults with 47,XXY Klinefelter syndrome","volume":"184","author":"Zitzmann","year":"2020","unstructured":"Zitzmann M & Rohayem J. Gonadal dysfunction and beyond: clinical challenges in children, adolescents, and adults with 47,XXY Klinefelter syndrome. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics2020184302\u2013312. (https:\/\/doi.org\/10.1002\/ajmg.c.31786)"},{"key":"bib54","article-title":"Manuscript A. of the 2022 3rd International Workshop on Klinefelter syndrome , XYY and Trisomy X The 3rd International Workshop on Klinefelter Syndrome, Trisomy X , and 47 , XYY syndrome was held in Leiden, the Netherlands, on September 12-14, 2022","unstructured":"Manuscript A. of the 2022 3rd International Workshop on Klinefelter syndrome , XYY and Trisomy X The 3rd International Workshop on Klinefelter Syndrome, Trisomy X , and 47 , XYY syndrome was held in Leiden, the Netherlands, on September 12-14, 2022. Here, we revi 1720, pp. 0\u20133 2023."},{"key":"bib55","series-title":"Pediatric Endocrinology Reviews: PER","first-page":"145","article-title":"Considerations for androgen therapy in children and adolescents with Klinefelter syndrome (47, XXY)","volume":"8","author":"Rogol","year":"2010","unstructured":"Rogol AD & Tartaglia N.   Considerations for androgen therapy in children and adolescents with Klinefelter syndrome (47, XXY). Pediatric Endocrinology Reviews: PER20108145\u2013150."},{"key":"bib56","series-title":"Archives of Disease in Childhood","first-page":"1","article-title":"Klinefelter syndrome: going beyond the diagnosis","author":"Butler","year":"2022","unstructured":"Butler GSrirangalingam UFaithfull JSangster PSenniappan S & Mitchell R. Klinefelter syndrome: going beyond the diagnosis. Archives of Disease in Childhood20221\u20136. (https:\/\/doi.org\/10.1136\/archdischild-2020-320831)"},{"key":"bib57","series-title":"Current Opinion in Endocrinology, Diabetes, and Obesity","first-page":"60","article-title":"Endocrine aspects of Klinefelter syndrome","volume":"26","author":"Lizarazo","year":"2019","unstructured":"Lizarazo AHMcLoughlin M & Vogiatzi MG. Endocrine aspects of Klinefelter syndrome. Current Opinion in Endocrinology, Diabetes, and Obesity20192660\u201365. (https:\/\/doi.org\/10.1097\/MED.0000000000000454)"},{"key":"bib58","series-title":"Journal of Pediatrics","first-page":"193","article-title":"Androgen treatment effects on motor function, cognition, and behavior in boys with Klinefelter syndrome","volume":"185","author":"Ross","year":"2017","unstructured":"Ross JLKushner HKowal KBardsley MDavis SReiss ALTartaglia N & Roeltgen D. Androgen treatment effects on motor function, cognition, and behavior in boys with Klinefelter syndrome. Journal of Pediatrics2017185193\u2013199.e4. (https:\/\/doi.org\/10.1016\/j.jpeds)"}],"container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/12\/7\/EC-23-0031.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/12\/7\/EC-23-0031.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/12\/7\/EC-23-0031.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:46:19Z","timestamp":1784555179000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/1194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,3]]},"references-count":58,"journal-issue":{"issue":"7"},"URL":"https:\/\/doi.org\/10.1530\/ec-23-0031","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,3]]}}}