Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment
IntroductionImpaired testosterone secretion is a frequent sequela following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.MethodsMonocentric, retrospective analysis. Male patients transplanted...
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Endocrinology |
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| author | Alessandro Cattoni Alessandro Cattoni Maria Laura Nicolosi Giulia Capitoli Alberto Gadda Silvia Molinari Sotiris Louka Andrea Buonsante Simona Orlandi Gianluca Salierno Iacopo Bellani Francesca Vendemini Giorgio Ottaviano Alberto Gaiero Graziella Fichera Andrea Biondi Andrea Biondi Adriana Balduzzi Adriana Balduzzi |
| author_facet | Alessandro Cattoni Alessandro Cattoni Maria Laura Nicolosi Giulia Capitoli Alberto Gadda Silvia Molinari Sotiris Louka Andrea Buonsante Simona Orlandi Gianluca Salierno Iacopo Bellani Francesca Vendemini Giorgio Ottaviano Alberto Gaiero Graziella Fichera Andrea Biondi Andrea Biondi Adriana Balduzzi Adriana Balduzzi |
| author_sort | Alessandro Cattoni |
| collection | DOAJ |
| description | IntroductionImpaired testosterone secretion is a frequent sequela following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.MethodsMonocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 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.ResultsOf 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 (p 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 (p<0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan (p 0.024). Chemo-only regimens were associated with statistically larger TV (p <0.001), higher testosterone (p 0.008) and lower gonadotropin levels (p <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).Conclusionsa) 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. |
| first_indexed | 2024-03-08T23:53:04Z |
| format | Article |
| id | doaj.art-b7575bbf3fb34f0b8c83866cb7a1b060 |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-08T23:53:04Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-b7575bbf3fb34f0b8c83866cb7a1b0602023-12-13T09:51:42ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12926831292683Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessmentAlessandro Cattoni0Alessandro Cattoni1Maria Laura Nicolosi2Giulia Capitoli3Alberto Gadda4Silvia Molinari5Sotiris Louka6Andrea Buonsante7Simona Orlandi8Gianluca Salierno9Iacopo Bellani10Francesca Vendemini11Giorgio Ottaviano12Alberto Gaiero13Graziella Fichera14Andrea Biondi15Andrea Biondi16Adriana Balduzzi17Adriana Balduzzi18Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyBicocca Bioinformatics, Biostatistics and Bioimaging B4 Centre, University of Milano-Bicocca, Monza, ItalyBicocca Bioinformatics, Biostatistics and Bioimaging B4 Centre, University of Milano-Bicocca, Monza, ItalyDepartment of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyDepartment of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyDepartment of Pediatrics and Neonatology, IRCCS Gaslini Savona e Pietra Ligure, Savona, ItalyDepartment of Endocrinology, Ospedale San Paolo, Savona, ItalyDepartment of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyDepartment of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyIntroductionImpaired testosterone secretion is a frequent sequela following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty.MethodsMonocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 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.ResultsOf 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 (p 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 (p<0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan (p 0.024). Chemo-only regimens were associated with statistically larger TV (p <0.001), higher testosterone (p 0.008) and lower gonadotropin levels (p <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).Conclusionsa) 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1292683/fulltreosulfanbusulfantotal body irradiationhypogonadismgonadal disordershematopoietic stem cell transplantation |
| spellingShingle | Alessandro Cattoni Alessandro Cattoni Maria Laura Nicolosi Giulia Capitoli Alberto Gadda Silvia Molinari Sotiris Louka Andrea Buonsante Simona Orlandi Gianluca Salierno Iacopo Bellani Francesca Vendemini Giorgio Ottaviano Alberto Gaiero Graziella Fichera Andrea Biondi Andrea Biondi Adriana Balduzzi Adriana Balduzzi Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment Frontiers in Endocrinology treosulfan busulfan total body irradiation hypogonadism gonadal disorders hematopoietic stem cell transplantation |
| title | Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment |
| title_full | Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment |
| title_fullStr | Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment |
| title_full_unstemmed | Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment |
| title_short | Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment |
| title_sort | pubertal attainment and leydig cell function following pediatric hematopoietic stem cell transplantation a three decade longitudinal assessment |
| topic | treosulfan busulfan total body irradiation hypogonadism gonadal disorders hematopoietic stem cell transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1292683/full |
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