{"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":1790630000132,"version":"4.1.0"},"reference-count":21,"publisher":"The Endocrine Society","issue":"9","funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS050597"],"award-info":[{"award-number":["NS050597"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["2T32DK63687011A1"],"award-info":[{"award-number":["2T32DK63687011A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K23HD092588-01"],"award-info":[{"award-number":["K23HD092588-01"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institut de Recherche Endocrinienne et Metabolique"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Klinefelter syndrome (KS) is a common genetic condition in which males have an extra X chromosome. KS is associated with testosterone deficiency, neurodevelopmental delays, and cardiometabolic disorders. There has been recent interest in prepubertal androgen treatment; however, the effects on puberty and gonadal function are unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To compare onset of puberty and testicular function in prepubertal boys treated with 2 years of oxandrolone (Ox) vs placebo (Pl).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Double-blind, randomized, controlled trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Single tertiary care referral center.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Eighty prepubertal boys with KS; mean age: 8.0 \u00b1 2.2 years (range: 4 to 12).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>Ox 0.05 mg\/kg vs identical-appearing Pl capsule given for 2 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcome Measures<\/jats:title>\n                  <jats:p>Onset of gonadarche (testicular volume \u22654 mL) and onset of pubarche (Tanner 2 pubic hair); change in testicular hormone concentrations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Ox-treated group had 20.5 times higher odds of reaching gonadarche (OR 95% CI: 6.5, 77.8) and 28.1 times higher odds of reaching pubarche (OR 95% CI: 8.8, 110.4) during the 2-year study period after adjusting for baseline age. Gonadarche and pubarche both occurred at a younger age in the Ox group (gonadarche: 9.8 \u00b1 1.5 vs 12.1 \u00b1 1.0 years, P &amp;lt; 0.001; pubarche: 10.2 \u00b1 1.1 vs 11.6 \u00b1 1.3 years, P = 0.02). Serum concentrations of testicular hormones and gonadotropins were not different between groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Two years of Ox treatment in prepubertal boys with KS results in an increased risk of early gonadarche, on average 2 years earlier than in Pl-treated boys. Ox did not affect serum concentrations of testicular hormones.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2018-00682","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T20:01:00Z","timestamp":1529524860000},"page":"3449-3455","source":"Crossref","is-referenced-by-count":19,"title":["Oxandrolone Treatment Results in an Increased Risk of Gonadarche in Prepubertal Boys With Klinefelter Syndrome"],"prefix":"10.1210","volume":"103","author":[{"given":"Shanlee M","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado"},{"name":"Section of Pediatric Endocrinology, Children\u2019s Hospital Colorado, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najiba","family":"Lahlou","sequence":"additional","affiliation":[{"name":"Hopital Cochin, Laboratoire d\u2019Hormonologie, Paris, France"},{"name":"BPR Clinical Laboratories, Pannes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Cox-Martin","sequence":"additional","affiliation":[{"name":"Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS) Program, University of Colorado School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kowal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pennsylvania"},{"name":"A.I. DuPont Hospital for Children, Wilmington, Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S","family":"Zeitler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado"},{"name":"Section of Pediatric Endocrinology, Children\u2019s Hospital Colorado, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith L","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pennsylvania"},{"name":"A.I. DuPont Hospital for Children, Wilmington, Delaware"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2018,6,20]]},"reference":[{"issue":"1","key":"2020071621401483800_B1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.yapd.2016.04.020","article-title":"Advances in the interdisciplinary care of children with Klinefelter syndrome","volume":"63","author":"Davis","year":"2016","journal-title":"Adv Pediatr"},{"issue":"2","key":"2020071621401483800_B2","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 Metab"},{"key":"2020071621401483800_B3","first-page":"193","article-title":"Androgen treatment effects on motor function, cognition, and behavior in boys with Klinefelter syndrome","volume-title":"J Pediatr","author":"Ross","year":"2017"},{"issue":"2","key":"2020071621401483800_B4","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/ajmg.c.31437","article-title":"Positive effects of early androgen therapy on the behavioral phenotype of boys with 47,XXY","volume":"169","author":"Samango-Sprouse","year":"2015","journal-title":"Am J Med Genet C Semin Med Genet"},{"issue":"3","key":"2020071621401483800_B5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/ajmg.a.35769","article-title":"Positive effects of short course androgen therapy on the neurodevelopmental outcome in boys with 47,XXY syndrome at 36 and 72 months of age","volume":"161A","author":"Samango-Sprouse","year":"2013","journal-title":"Am J Med Genet A"},{"issue":"1","key":"2020071621401483800_B6","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","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2020071621401483800_B7","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ajmg.c.31350","article-title":"Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome","volume":"163C","author":"Wosnitzer","year":"2013","journal-title":"Am J Med Genet C Semin Med Genet"},{"issue":"4","key":"2020071621401483800_B8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ecl.2015.07.008","article-title":"Testis development and fertility potential in boys with Klinefelter syndrome","volume":"44","author":"Davis","year":"2015","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"1","key":"2020071621401483800_B9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/humupd\/dmi039","article-title":"Natural history of seminiferous tubule degeneration in Klinefelter syndrome","volume":"12","author":"Aksglaede","year":"2006","journal-title":"Hum Reprod Update"},{"issue":"3","key":"2020071621401483800_B10","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/andr.12208","article-title":"The Klinefelter syndrome: current management and research challenges","volume":"4","author":"Nieschlag","year":"2016","journal-title":"Andrology"},{"issue":"6","key":"2020071621401483800_B11","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/j.1651-2227.2011.02184.x","article-title":"Testosterone and the child (0-12 years) with Klinefelter syndrome (47XXY): a review","volume":"100","author":"Fennoy","year":"2011","journal-title":"Acta Paediatr"},{"issue":"6","key":"2020071621401483800_B12","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1111\/andr.12275","article-title":"Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome","volume":"4","author":"Davis","year":"2016","journal-title":"Andrology"},{"issue":"7","key":"2020071621401483800_B13","doi-asserted-by":"crossref","first-page":"725","DOI":"10.2165\/00003495-200464070-00004","article-title":"The anabolic androgenic steroid oxandrolone in the treatment of wasting and catabolic disorders: review of efficacy and safety","volume":"64","author":"Orr","year":"2004","journal-title":"Drugs"},{"issue":"1","key":"2020071621401483800_B14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13633-015-0013-3","article-title":"Effect of oxandrolone therapy on adult height in Turner syndrome patients treated with growth hormone: a meta-analysis","volume":"2015","author":"Sheanon","year":"2015","journal-title":"Int J Pediatr Endocrinol"},{"issue":"6","key":"2020071621401483800_B15","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1159\/000315482","article-title":"A double-blind, placebo-controlled comparison of letrozole to oxandrolone effects upon growth and puberty of children with constitutional delay of puberty and idiopathic short stature","volume":"74","author":"Salehpour","year":"2010","journal-title":"Horm Res Paediatr"},{"issue":"2","key":"2020071621401483800_B16","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1046\/j.1365-2265.1997.t01-1-1150928.x","article-title":"Effect of low dose oxandrolone and testosterone treatment on the pituitary-testicular and GH axes in boys with constitutional delay of growth and puberty","volume":"46","author":"Crowne","year":"1997","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"7","key":"2020071621401483800_B17","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1136\/adc.66.7.841","article-title":"Treatment of constitutional growth delay in prepubertal boys with a prolonged course of low dose oxandrolone","volume":"66","author":"Papadimitriou","year":"1991","journal-title":"Arch Dis Child"},{"issue":"4","key":"2020071621401483800_B18","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.jamcollsurg.2011.12.038","article-title":"Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy","volume":"214","author":"Porro","year":"2012","journal-title":"J Am Coll Surg"},{"issue":"5","key":"2020071621401483800_B19","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1210\/jcem-58-5-857","article-title":"True precocious puberty complicating congenital adrenal hyperplasia: treatment with a luteinizing hormone-releasing hormone analog","volume":"58","author":"Pescovitz","year":"1984","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"2020071621401483800_B20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.6065\/apem.2016.21.3.136","article-title":"Etiology and therapeutic outcomes of children with gonadotropin-independent precocious puberty","volume":"21","author":"Kang","year":"2016","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"2020071621401483800_B21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jad.2013.10.034","article-title":"Pubertal timing in girls and depression: a systematic review","volume":"155","author":"Galvao","year":"2014","journal-title":"J Affect Disord"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/103\/9\/3449\/25685913\/jc.2018-00682.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/103\/9\/3449\/25685913\/jc.2018-00682.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T09:22:52Z","timestamp":1594977772000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/103\/9\/3449\/5040363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,20]]},"references-count":21,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2018-00682","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,9]]},"published":{"date-parts":[[2018,6,20]]}}}