{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:30:00Z","timestamp":1768566600274,"version":"3.49.0"},"posted":{"date-parts":[[2024,12,10]]},"group-title":"Endocrinology (including Diabetes Mellitus and Metabolic Disease)","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>47,XXY\/Klinefelter syndrome (XXY) is associated with impaired testicular function and differences in physical growth, metabolism, and neurodevelopment. Clinical features of XXY may be attributable to inadequate testosterone during the mini-puberty period of infancy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We tested the hypothesis that exogenous testosterone treatment positively effects short-term physical, hormonal, and neurodevelopmental outcomes in infants with XXY.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Double-blind randomized controlled trial, 2017-2021<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>US tertiary care pediatric hospital<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Infants 30-90 days of age with prenatally identified, non-mosaic 47,XXY (n=71).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>Testosterone cypionate 25mg intramuscular injections every 4 weeks for 3 doses<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Main outcome measures<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>a priori<\/jats:italic>\n                    primary outcomes were change in percent fat mass (%FM) z-scores and change in the total composite percentile on Alberta Infant Motor Scales (AIMS) assessment from baseline to 12 weeks.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The between group difference in change in %FM z-scores was -0.57 [95% CI -1.1, - 0.06], p=0.03), secondary to greater increases in lean mass in the testosterone-treated group (1.5\u00b10.4 kg vs 1.2\u00b10.4, p=0.001). Testosterone suppressed gonadotropins and inhibin B (p&lt;0.001 for all). In contrast, there were no significant group differences in short term motor, cognitive, or language outcomes (p&gt;0.15 for all).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In this double-blind randomized controlled trial in infants with XXY, testosterone injections resulted in physical effects attributable to systemic androgen exposure; however, there was no impact on neurodevelopmental outcomes and the hypothalamic-pituitary-gonadal axis was suppressed. These results do not support routine testosterone treatment in infants with XXY, however long term follow up on physical health, neurodevelopment and testicular function is needed.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.12.09.24318726","type":"posted-content","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T19:20:23Z","timestamp":1733858423000},"source":"Crossref","is-referenced-by-count":0,"title":["Testosterone Effects on Short-Term Physical, Hormonal, and Neurodevelopmental Outcomes in Infants with 47,XXY\/Klinefelter Syndrome: The TESTO Randomized Controlled Trial"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0304-9550","authenticated-orcid":false,"given":"Shanlee","family":"Davis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-2165","authenticated-orcid":false,"given":"Susan","family":"Howell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-0947","authenticated-orcid":false,"given":"Jennifer","family":"Janusz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1365-6466","authenticated-orcid":false,"given":"Najiba","family":"Lahlou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6512-9743","authenticated-orcid":false,"given":"Talia","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-7308","authenticated-orcid":false,"given":"Karli","family":"Swenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0464-229X","authenticated-orcid":false,"given":"Rebecca","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8613-2498","authenticated-orcid":false,"given":"Judith","family":"Ross","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-7858","authenticated-orcid":false,"given":"Philip","family":"Zeitler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-6722","authenticated-orcid":false,"given":"Nicole","family":"Tartaglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"2","key":"2025020921100574000_2024.12.09.24318726v2.1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000479460","article-title":"Non-Invasive Prenatal Testing for Sex Chromosome Aneuploidy in Routine Clinical Practice","volume":"44","year":"2018","journal-title":"Fetal diagnosis and therapy"},{"key":"2025020921100574000_2024.12.09.24318726v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.09.007"},{"issue":"6","key":"2025020921100574000_2024.12.09.24318726v2.3","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","year":"2011","journal-title":"Acta paediatrica"},{"key":"2025020921100574000_2024.12.09.24318726v2.4","doi-asserted-by":"crossref","unstructured":"Pacenza N , Pasqualini T , Gottlieb S , Knoblovits P , Costanzo PR , Stewart Usher J , Rey RA , Martinez MP , Aszpis S . 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