{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:18Z","timestamp":1788761298668,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>A critical proportion of childhood bone and soft tissue sarcoma survivors experience some form of reproductive impairment. These findings underscore the increasing need for a comprehensive evaluation of gonadal function in this patient population. This study aimed to evaluate gonadal function in survivors of childhood bone and soft tissue sarcomas and to identify treatment-related risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included survivors aged 17 years or older at evaluation who had received curative-intent treatment for bone or soft tissue sarcomas diagnosed between January 2009 and February 2022. Demographics, clinical history, hormonal assays [follicle-stimulating hormone (FSH), luteinizing hormone, anti-M\u00fcllerian hormone (AMH), inhibin B, estradiol, testosterone], pelvic ultrasonography (females), and semen analysis (males) were recorded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort comprised 38 participants (median age 18.75 years); 17 males (44.74%) and 21 females (55.26%). Gonadal dysfunction was observed in 18 participants (47.4%), including low ovarian reserve or diminished AMH as the most common finding in females and azoospermia as the most frequent abnormality in males. Normal gonadal function was preserved in 20 participants (52.6%). FSH levels were significantly higher in the gonadal dysfunction group in both females (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.004) and males (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.007).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Childhood sarcoma survivors have a high prevalence of gonadal dysfunction, with notable impairments in ovarian reserve and spermatogenesis, marked by elevated FSH in both sexes. Routine surveillance, patient education on gonadotoxicity and infertility risks, and pre-treatment fertility preservation counseling are essential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1914861","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:33:58Z","timestamp":1788759238000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High prevalence of gonadal dysfunction in pediatric sarcoma survivors: insights from hormonal and clinical markers"],"prefix":"10.3389","volume":"14","author":[{"given":"Selma","family":"Cakmakci","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Kilinc Ugurlu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Gazi University Faculty of Medicine","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadide Basak","family":"Gulleroglu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derya Ozdemir","family":"Tas","sequence":"additional","affiliation":[{"name":"Center for Assisted Reproduction, Ankara City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem","family":"Bulut","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Tekirdag Ismail Fehmi Cumalioglu City Hospital","place":["Tekirdag, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Caner","family":"Ozer","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Health Sciences University Gulhane Faculty of Medicine","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Yazal Erdem","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derya","family":"Ozyoruk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Gurbuz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Boyraz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inci Ergurhan","family":"Ilhan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neriman","family":"Sari","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Ankara Bilkent City Hospital","place":["Ankara, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3238\/arztebl.2012.0124","article-title":"Fertility in survivors of childhood cancer","volume":"109","author":"Spix","year":"2012","journal-title":"Dtsch Arztebl Int"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e75","DOI":"10.1016\/S1470-2045(17)30026-8","article-title":"Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the international late effects of childhood cancer guideline harmonization group in collaboration with the PanCareSurFup consortium","volume":"18","author":"Skinner","year":"2017","journal-title":"Lancet Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e70805","DOI":"10.1002\/cam4.70805","article-title":"Association between treatment of childhood cancer and its late effects on gonadal or growth function in childhood cancer survivors: a retrospective observational study","volume":"14","author":"Urakawa","year":"2025","journal-title":"Cancer Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"992","DOI":"10.4143\/crt.2022.1518","article-title":"Gonadal function in female adolescent and young adult survivors of childhood cancer","volume":"55","author":"Jin","year":"2023","journal-title":"Cancer Res Treat"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1200\/JCO.2017.76.3441","article-title":"Reproductive function and outcomes in female survivors of childhood, adolescent, and young adult cancer: a review","volume":"36","author":"van Dorp","year":"2018","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1097\/AOG.0b013e3181f87c4b","article-title":"Reproductive outcomes for survivors of childhood cancer","volume":"116","author":"Hudson","year":"2010","journal-title":"Obstet Gynecol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/1097-0142(20010201)91:3<613::AID-CNCR1042>3.0.CO;2-R","article-title":"High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood","volume":"91","author":"Kenney","year":"2001","journal-title":"Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/pbc.21323","article-title":"Does ifosfamide affect gonadal function?","volume":"50","author":"Williams","year":"2008","journal-title":"Pediatr Blood Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1002\/pbc.22004","article-title":"Male gonadal toxicity","volume":"53","author":"Meistrich","year":"2009","journal-title":"Pediatr Blood Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/pbc.21780","article-title":"Effect of childhood cancer treatment on fertility markers in adult male long-term survivors","volume":"52","author":"Van Casteren","year":"2009","journal-title":"Pediatr Blood Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S1462-3889(02)00081-9","article-title":"The effect of cytotoxic chemotherapy on female fertility","volume":"7","author":"Chasle","year":"2003","journal-title":"Eur J Oncol Nurs"},{"key":"B12","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1111\/j.1651-2227.2008.00784.x","article-title":"Male reproductive health after childhood cancer","volume":"97","author":"L\u00e4hteenm\u00e4ki","year":"2008","journal-title":"Acta Paediatr"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1016\/j.ejca.2012.12.007","article-title":"Gonadal function recovery in very long-term male survivors of childhood cancer","volume":"49","author":"van Dorp","year":"2013","journal-title":"Eur J Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s00432-016-2124-5","article-title":"Gonadal status in long-term male survivors of childhood cancer","volume":"142","author":"Brignardello","year":"2016","journal-title":"J Cancer Res Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.17925\/EE.2022.18.2.122","article-title":"Review of the function of the hypothalamic-pituitary-gonadal axis in children and adolescents with cancer","volume":"18","author":"Dacal","year":"2022","journal-title":"Eur Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1007\/BF02002903","article-title":"Gonadal function of young adults after therapy of malignancies during childhood or adolescence","volume":"155","author":"M\u00fcller","year":"1996","journal-title":"Eur J Pediatr"},{"key":"B17","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1089\/jayao.2019.0138","article-title":"Dissociation of pubertal development abnormality and gonadal dysfunction in childhood cancer survivors","volume":"9","author":"Yu","year":"2020","journal-title":"J Adolesc Young Adult Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1002\/ijc.70260","article-title":"Fertility preservation in women with sarcoma: a real-world experience","volume":"158","author":"Beinse","year":"2026","journal-title":"Int J Cancer"},{"key":"B19","doi-asserted-by":"publisher","first-page":"951","DOI":"10.21037\/tau.2017.07.03","article-title":"Oncofertility in sarcoma patients","volume":"6","author":"Lopategui","year":"2017","journal-title":"Transl Androl Urol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1080\/13577149877939","article-title":"Outcome and toxicity of an Ifosfamide-based soft tissue sarcoma treatment protocol in children. The importance of local therapy","volume":"2","author":"Yule","year":"1998","journal-title":"Sarcoma"},{"key":"B21","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1097\/01.blo.0000137547.14953.1e","article-title":"Chemotherapy for bone sarcoma does not affect fertility rates or childbirth","volume":"428","author":"Hosalkar","year":"2004","journal-title":"Clin Orthop Relat Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"280","DOI":"10.4274\/jcrpe.2183","article-title":"Reference values for weight, height, head circumference, and body mass index in Turkish children","volume":"7","author":"Neyzi","year":"2015","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1136\/adc.45.239.13","article-title":"Variations in the pattern of pubertal changes in boys","volume":"45","author":"Marshall","year":"1970","journal-title":"Arch Dis Child"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4931","DOI":"10.1210\/jc.2009-1342","article-title":"Prenatal determinants of uterine volume and ovarian reserve in adolescence","volume":"94","author":"Hart","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B25","doi-asserted-by":"publisher","first-page":"4059","DOI":"10.1210\/jcem.82.12.4456","article-title":"Inhibin B as a serum marker of spermatogenesis: correlation to differences in sperm concentration and follicle-stimulating hormone levels. A study of 349 Danish men","volume":"82","author":"Jensen","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3110","DOI":"10.1210\/jcem.83.9.5121","article-title":"Serum inhibin B as a marker of spermatogenesis","volume":"83","author":"Pierik","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/S0015-0282(02)04259-0","article-title":"Serum levels of inhibin B and follicle-stimulating hormone may predict successful sperm retrieval in men with azoospermia who are undergoing testicular sperm extraction","volume":"78","author":"Bohring","year":"2002","journal-title":"Fertil Steril"},{"key":"B28","volume-title":"WHO Laboratory Manual for the Examination and Processing of Human Semen","year":"2021"},{"key":"B29","doi-asserted-by":"publisher","first-page":"168","DOI":"10.6065\/apem.2013.18.4.168","article-title":"Reduced male fertility in childhood cancer survivors","volume":"18","author":"Lee","year":"2013","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1089\/jayao.2018.0080","article-title":"Early detection of ovarian dysfunction by anti-mullerian hormone in adolescent and young adult-aged survivors of childhood cancer","volume":"8","author":"George","year":"2019","journal-title":"J Adolesc Young Adult Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1093\/humrep\/den487","article-title":"Assessment of ovarian reserve in adult childhood cancer survivors using anti-M\u00fcllerian hormone","volume":"24","author":"Lie Fong","year":"2008","journal-title":"Hum Reprod"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1093\/humrep\/deg473","article-title":"Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-M\u00fcllerian hormone, inhibin B and ovarian ultrasound","volume":"18","author":"Bath","year":"2003","journal-title":"Hum Reprod"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e4512","DOI":"10.1097\/MD.0000000000004512","article-title":"Severe gonadotoxic insult manifests early in young girls treated for ewing sarcoma","volume":"95","author":"M\u00f6rse","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1089\/jayao.2024.0093","article-title":"A mega-analysis of anti-m\u00fcllerian hormone levels in female childhood cancer survivors based on treatment risk, time since treatment, and pubertal status","volume":"14","author":"Yano Maher","year":"2025","journal-title":"J Adolesc Young Adult Oncol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1089\/jayao.2024.0057","article-title":"Systematic review of the gonadotoxicity and risk of infertility of soft tissue sarcoma chemotherapies in pre- and postpubertal females and males","volume":"13","author":"Steinmann","year":"2024","journal-title":"J Adolesc Young Adult Oncol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1089\/jayao.2023.0185","article-title":"A systematic review of the gonadotoxicity of osteosarcoma and ewing\u2019s sarcoma chemotherapies in postpubertal females and males","volume":"13","author":"Weidlinger","year":"2024","journal-title":"J Adolesc Young Adult Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1501364","DOI":"10.3389\/fimmu.2024.1501364","article-title":"Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy","volume":"15","author":"Yalcinkaya","year":"2025","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"367","DOI":"10.3892\/mco.2014.474","article-title":"Fertility following treatment of high-grade malignant bone and soft tissue tumors in young adults","volume":"3","author":"Hoshi","year":"2015","journal-title":"Mol Clin Oncol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.2174\/1871520621666210811105344","article-title":"Alkylating agents, the road less traversed, changing anticancer therapy","volume":"22","author":"Karati","year":"2022","journal-title":"Anticancer Agents Med Chem"},{"key":"B40","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1177\/10849785251376173","article-title":"An update on alkylating agents in breast cancer therapy","volume":"40","author":"Shaik","year":"2025","journal-title":"Cancer Biother Radiopharm"},{"key":"B41","author":"Craft","year":"2023"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1007\/s40618-022-01778-7","article-title":"The impact of male factors and their correct and early diagnosis in the infertile couple\u2019s pathway: 2021 perspectives","volume":"45","author":"Pallotti","year":"2022","journal-title":"J Endocrinol Invest"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1007\/s00277-025-06275-4","article-title":"Fertility assessment in long-term young female survivors with hematological disease after allogeneic hematopoietic cell transplantation: a single-center real-life cross-sectional study","volume":"104","author":"Hou","year":"2025","journal-title":"Ann Hematol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.anpede.2023.11.007","article-title":"Primary ovarian insufficiency in cancer survivors: keys to optimal management","volume":"99","author":"Colino","year":"2023","journal-title":"An Pediatr"},{"key":"B45","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1093\/humupd\/dmac004","article-title":"Anti-M\u00fcllerian hormone as a marker of ovarian reserve and premature ovarian insufficiency in children and women with cancer: a systematic review","volume":"28","author":"Anderson","year":"2022","journal-title":"Hum Reprod Update"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1914861\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:33:59Z","timestamp":1788759239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1914861\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":45,"alternative-id":["10.3389\/fped.2026.1914861"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1914861","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"1914861"}}