{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:42:45Z","timestamp":1789094565847,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Impaired testosterone secretion is a frequent\n                      <jats:italic>sequela<\/jats:italic>\n                      following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Monocentric, retrospective analysis. Male patients transplanted &amp;lt;18 years between 1992 and 2021, surviving \u22652 years after HSCT and showing, upon enrollment, clinical and biochemical signs consistent with pubertal onset and progression were included. Clinical and biochemical data collected every 6-12 months were recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 130 patients enrolled, 56% were prepubertal, while 44% were peri-\/postpubertal upon HSCT. Overall, 44% showed spontaneous progression into puberty and normal gonadal profile, while the remaining experienced pubertal arrest (1%), isolated increase of FSH (19%), compensated (23%) or overt (13%) hypergonadotropic hypogonadism. Post-pubertal testicular volume (TV) was statistically smaller among patients still pre-pubertal upon HSCT (\n                      <jats:italic>p<\/jats:italic>\n                      0.049), whereas no differences were recorded in adult testosterone levels. LH and testosterone levels showed a specular trend between 20 and 30 years, as a progressive decrease in sexual steroids was associated with a compensatory increase of the luteinizing hormone. A variable degree of gonadal dysfunction was reported in 85%, 51%, 32% and 0% of patients following total body irradiation- (TBI), busulfan-, cyclophosphamide- and treosulfan-based regimens, respectively. TBI and busulfan cohorts were associated with the lowest probability of gonadal event-free course (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt;0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan (\n                      <jats:italic>p<\/jats:italic>\n                      0.024). Chemo-only regimens were associated with statistically larger TV (\n                      <jats:italic>p &amp;lt;<\/jats:italic>\n                      0.001), higher testosterone (\n                      <jats:italic>p<\/jats:italic>\n                      0.008) and lower gonadotropin levels (\n                      <jats:italic>p &amp;lt;<\/jats:italic>\n                      0.001) than TBI. Accordingly, the latter was associated with a 2-fold increase in the risk of gonadal failure compared to busulfan (OR 2.34, CI 1.08-8.40), whereas being pre-pubertal upon HSCT was associated with a reduced risk (OR 0.15, CI 0.08-0.30).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>a) patients pre-pubertal upon HSCT showed a reduced risk of testicular endocrine dysfunction, despite smaller adult TV; b) patients showed downwards trend in testosterone levels after full pubertal attainment, despite a compensatory increase in LH; c) treosulfan was associated to a statistically lower occurrence of hypogonadism than busulfan, with a trend towards larger TV, higher testosterone levels and lower gonadotropins.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2023.1292683","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:53:48Z","timestamp":1702443228000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment"],"prefix":"10.3389","volume":"14","author":[{"given":"Alessandro","family":"Cattoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Nicolosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Capitoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Gadda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Molinari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotiris","family":"Louka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Buonsante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Orlandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Salierno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Bellani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vendemini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Ottaviano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Gaiero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Fichera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Balduzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052638","article-title":"Hematopoietic stem-cell transplantation","volume":"354","author":"Copelan","year":"2006","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/sj.bmt.1705992","article-title":"Pediatric blood and marrow transplantation: state of the science","volume":"41","author":"Cairo","year":"2008","journal-title":"Bone Marrow Transplant"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30665","article-title":"An estimate of the number of people in Italy living after a childhood cancer","volume":"140","author":"Francisci","year":"2017","journal-title":"Int J Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-023-01926-4","article-title":"Decision making on HSCT in patients with hemoglobinopathies; 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