{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:12:54Z","timestamp":1788437574909,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL) affect young women, with cure rates exceeding 80%. Treatment-related gonadal insufficiency is recognized for its impact on fertility, yet fertility preservation remains underutilized, and prospective data are limited. The aim of this study is to prospectively evaluate gonadal function in women \u226440 years old with lymphoma undergoing chemotherapy. Methods: Ovarian reserve and endocrine ovarian function were evaluated by sequential measurements of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-M\u00fcllerian hormone (AMH), progesterone, and estradiol at diagnosis, during, and after chemotherapy. Results: 81 female patients \u226440 years old were enrolled, including 53 with HL and 28 with NHL (16 with PMBCL). HL patients had significantly lower AMH values for their respective age group compared to all other diagnoses (p = 0.05), which was more striking for patients \u226430 years old (p = 0.039), indicating pre-existing reduced ovarian reserve in HL. In HL, both FSH and AMH levels indicate gonadal dysfunction for at least six months post-chemotherapy, with AMH serving as a more sensitive biomarker than FSH. For PMBCL patients treated with R-DA-EPOCH, AMH suppression was noticed, with no evidence of recovery up to 18 months post-treatment. At all time points, the PMBCL patients had significantly lower AMH values compared to the HL patients (AMH6: p = 0.03, AMH12 and AMH18: p = 0.05). AMH emerged as the most sensitive marker of ovarian damage, with pretreatment levels &lt;7 pmol\/L predicting impaired ovarian reserve in HL patients. Conclusions: For HL, the pretreatment cut-off of 7 pmol\/L could discriminate patients with ovarian insufficiency post-treatment, whereas no statistically significant predictive association was identified in PMBCL. These findings require validation in larger cohorts.<\/jats:p>","DOI":"10.3390\/cancers18172855","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:08:53Z","timestamp":1788433733000},"page":"2855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Chemotherapy on Gonadal Function in Female Patients with Hodgkin and Non-Hodgkin Lymphoma: A Comprehensive Analysis of Hormonal Kinetics and Implications for Fertility and Contraceptive Planning"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6945-3612","authenticated-orcid":false,"given":"Angeliki N.","family":"Georgopoulou","sequence":"first","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-1853","authenticated-orcid":false,"given":"Theodoros P.","family":"Vassilakopoulos","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Giannakou","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neoklis A.","family":"Georgopoulos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, University of Patras Medical School, 26110 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0590-1575","authenticated-orcid":false,"given":"Sophia","family":"Kalantaridou","sequence":"additional","affiliation":[{"name":"B Obstetrics and Gynecology Department, Attikon General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Keramaris","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Lalou","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Loukari","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Konstantopoulos","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina P.","family":"Siakantaris","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2913-7887","authenticated-orcid":false,"given":"Anastasia","family":"Kopsaftopoulou","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8934-0342","authenticated-orcid":false,"given":"Chrysovalanto","family":"Chatzidimitriou","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Arapaki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Belia","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iliana","family":"Konstantinou","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1118-1700","authenticated-orcid":false,"given":"Ioannis","family":"Asimakopoulos","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-887X","authenticated-orcid":false,"given":"Irene","family":"Mammali","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, University of Patras Medical School, 26110 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria K.","family":"Angelopoulou","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, School of Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1200\/JCO.2016.70.9410","article-title":"Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: Updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials","volume":"35","author":"Sasse","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2040620720902911","DOI":"10.1177\/2040620720902911","article-title":"Optimizing outcomes in relapsed\/refractory Hodgkin lymphoma: A review of current and forthcoming therapeutic strategies","volume":"11","author":"Vassilakopoulos","year":"2020","journal-title":"Ther. Adv. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liaskas, A., Dimopoulou, M.N., Piperidou, A., Angelopoulou, M.K., and Vassilakopoulos, T.P. (2025). Current Issues and Future Perspectives of Targeted Therapies in Primary Mediastinal Large B-Cell Lymphoma. J. Clin. Med., 14.","DOI":"10.3390\/jcm14041191"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1200\/JCO.2010.32.8427","article-title":"Long-term complications of lymphoma and its treatment","volume":"29","author":"Ng","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e506","DOI":"10.1016\/j.clml.2020.03.006","article-title":"Long-term Hodgkin Lymphoma Survivors: A Glimpse of What Happens 10 Years After Treatment","volume":"20","author":"Laddaga","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.bpobgyn.2011.11.008","article-title":"Chemotherapy and fertility","volume":"26","author":"Blumenfeld","year":"2012","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3978","DOI":"10.1182\/bloodadvances.2021005557","article-title":"Hodgkin lymphoma and female fertility: A multicenter study in women treated with ABVD","volume":"7","author":"Machet","year":"2022","journal-title":"Blood Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1182\/blood-2007-02-073544","article-title":"Fertility in male patients with advanced Hodgkin lymphoma treated with BEACOPP: A report of the German Hodgkin Study Group (GHSG)","volume":"111","author":"Sieniawski","year":"2008","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.3109\/10428194.2015.1118476","article-title":"Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B-cell lymphomas","volume":"57","author":"Gharwan","year":"2016","journal-title":"Leuk. Lymphoma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1200\/JCO.2011.37.1989","article-title":"Premature ovarian failure and fertility in long-term survivors of Hodgkin\u2019s lymphoma: A European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d\u2019\u00c9Tude des Lymphomes de l\u2019Adulte Cohort Study","volume":"30","author":"Heutte","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1200\/JCO.2012.44.3721","article-title":"Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin study group HD13 to HD15 Trials","volume":"31","author":"Behringer","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1093\/annonc\/mdr575","article-title":"Fertility and gonadal function in female survivors after treatment of early unfavorable hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial","volume":"23","author":"Behringer","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.3324\/haematol.2011.045856","article-title":"Management of fertility in patients treated for Hodgkin\u2019s lymphoma","volume":"96","author":"Harel","year":"2011","journal-title":"Haematologica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/humupd\/dmac045","article-title":"Anti-M\u00fcllerian hormone for the diagnosis and prediction of menopause: A systematic review","volume":"29","author":"Nelson","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"ref_15","unstructured":"Plus, E.A.M.H., and Rii, A.M.H. (2026, August 30). Elecsys AMH Plus 08818916190. 1\u20138. Available online: https:\/\/diagnostics.roche.com\/global\/en\/products\/lab\/elecsys-amh-plus-cps-000433.html."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.anireprosci.2010.08.030","article-title":"The normal menstrual cycle in women","volume":"124","author":"Mihm","year":"2011","journal-title":"Anim. Reprod. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Anderson, R.A., and Su, H.I. (2020). The Clinical Value and Interpretation of Anti-M\u00fcllerian Hormone in Women With Cancer. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.574263"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mce.2003.09.024","article-title":"Anti-M\u00fcllerian hormone and its role in ovarian function","volume":"211","author":"Gruijters","year":"2003","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.fertnstert.2020.09.134","article-title":"Testing and interpreting measures of ovarian reserve: A committee opinion","volume":"114","author":"Penzias","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ciccarone, M., Cavaceppi, P., Tesei, C., Brunetti, S., Pulsoni, A., Annibali, O., Gasparoli, C., Battistini, R., Hohaus, S., and Pelliccia, S. (2023). Effects of ABVD chemotherapy on ovarian function: Epidemiology, hormonal dosages and ultrasound morphologic analyses in 270 patients with Hodgkin\u2019s disease. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1059393"},{"key":"ref_21","first-page":"165","article-title":"Non-growing follicle density is increased following adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy in the adult human ovary","volume":"32","author":"McLaughlin","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1182\/blood-2017-09-772632","article-title":"Biology of classical Hodgkin lymphoma: Implications for prognosis and novel therapies","volume":"131","author":"Mottok","year":"2018","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12610-016-0031-x","article-title":"Semen quality of 4480 young cancer and systemic disease patients: Baseline data and clinical considerations","volume":"26","author":"Auger","year":"2016","journal-title":"Basic Clin. Androl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1182\/blood.V122.21.1779.1779","article-title":"Study On The Fertility Status Of Females With Primary Mediastinal B-Cell Lymphoma Following Treatment With Dose-Adjusted EPOCH-Rituximab","volume":"122","author":"Gharwan","year":"2013","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e965","DOI":"10.1097\/HS9.0000000000000965","article-title":"PET for Response Assessment to R-da-EPOCH in Primary Mediastinal Large B-cell lymphoma: Who Is Worthy to be Irradiated?","volume":"7","author":"Vassilakopoulos","year":"2023","journal-title":"HemaSphere"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Piperidou, A., Angelopoulou, M.K., Chatzidimitriou, C., Asimakopoulos, J.V., Arapaki, M., Panitsas, F., Tsourouflis, G., Belia, M., Konstantinou, I., and Kopsaftopoulou, A. (2025). Optimally Delivered R-da-EPOCH Versus R-CHOP-21 in Primary Mediastinal Large B-Cell Lymphoma: A Real-Life Comparison in a Single Academic Center. Cancers, 17.","DOI":"10.3390\/cancers17101699"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chatzidimitriou, C., Rondogianni, P., Arapaki, M., Liaskas, A., Plata, E., Angelopoulou, M.K., Tsirigotis, P., and Vassilakopoulos, T.P. (2021). Very Early Onset of Therapy-Related Acute Myeloid Leukemia with 11q23 Rearrangement Presenting with Unusual PET Findings after R-DA-EPOCH for Primary Mediastinal Large B-Cell Lymphoma. Medicina, 58.","DOI":"10.3390\/medicina58010048"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.fertnstert.2011.06.016","article-title":"Evaluation of serum antimullerian hormone and inhibin B concentrations in the differential diagnosis of secondary oligoamenorrhea","volume":"96","author":"Li","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Klonoff-Cohen, H., Polavarapu, M., and Ramachandran, N. (2025). Anti-Mullerian Hormone and conception timing as predictors of live births in cancer patients using fertility preservation: A systematic review. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1683794"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0140-6736(24)01315-1","article-title":"Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): A randomised, multicentre, parallel, open-label, phase 3 trial","volume":"404","author":"Borchmann","year":"2024","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/humupd\/dmn022","article-title":"GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy","volume":"14","author":"Blumenfeld","year":"2008","journal-title":"Hum. Reprod. Update"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1200\/JCO.2015.65.8864","article-title":"No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial","volume":"34","author":"Demeestere","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1200\/JCO-24-02782","article-title":"Fertility Preservation in People With Cancer: ASCO Guideline Update","volume":"43","author":"Su","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"hoaa052","DOI":"10.1093\/hropen\/hoaa052","article-title":"ESHRE guideline: Female fertility preservation","volume":"2020","author":"Anderson","year":"2020","journal-title":"Hum. Reprod. Open"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:16:23Z","timestamp":1788434183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":34,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172855"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172855","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}