title: Effect of childhood cancer treatment on fertility markers in adult male long-term survivors.
abstract: BACKGROUND
  Although it is accepted that pediatric cancer treatment harbors a risk of gonadal damage, large cohort studies using up-to-date fertility markers are lacking.
  
  
  METHODS
  The aim of our study was to evaluate the gonadal toxicity of childhood cancer treatment using fertility markers. We included 248 adult male long-term survivors of childhood cancer. Median age at diagnosis: 5 years, median age at follow-up: 24 years, median follow-up time 18 years. We evaluated patient characteristics, treatment modalities, testicular size, and endocrinological parameters including Inhibin B, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone.
  
  
  RESULTS
  The median value of Inhibin B in the cancer survivor group was 126 ng/L versus 177 ng/L in the control group (P < 0.001). In the survivors, 67% had Inhibin B levels below the normal reference value of 150 ng/L compared with 26% in the control group (P < 0.05). Inhibin B was the most sensitive discriminator between survivors and controls. Significantly decreased Inhibin B levels and increased FSH levels were found in men treated for Hodgkin and non-Hodgkin lymphoma, acute-myeloid leukemia, neuroblastoma, and sarcoma as compared to other malignancies. Cumulative dosages of procarbazine and cyclophosphamide were the only independent chemotherapy-related predictors for decrease of Inhibin B levels and increase of FSH. Age at time of treatment did not influence post-treatment Inhibin B or FSH levels.
  
  
  CONCLUSIONS
  Severe gonadal impairment is a risk in a considerable subgroup of childhood cancer survivors based on current fertility markers like Inhibin B. Males receiving gonadotoxic treatment before puberty are not protected from post treatment gonadal dysfunction.
authors.affiliation: Department of Urology, Section of Andrology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
authors.forename: Niels J
authors.initials: NJ
authors.lastname: van Casteren
authors.forename: Geert H M
authors.initials: GH
authors.lastname: van der Linden
authors.forename: Friederike G A J
authors.initials: FG
authors.lastname: Hakvoort-Cammel
authors.forename: Karel
authors.initials: K
authors.lastname: Hählen
authors.forename: Gert R
authors.initials: GR
authors.lastname: Dohle
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000009:adverse effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000032:analysis; D005500:Follow-Up Studies; D006066:Gonads / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007246:Infertility / Q000139:chemically induced / Q000175:diagnosis*; D007265:Inhibins / Q000032:analysis; D015470:Leukemia, Myeloid, Acute / Q000150:complications; D008223:Lymphoma / Q000150:complications; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000628:therapy; D009447:Neuroblastoma / Q000150:complications; D011344:Procarbazine / Q000009:adverse effects; D012509:Sarcoma / Q000150:complications; D017741:Survivors
chemical_list: D015415:Biomarkers; C422364:inhibin B; D011344:Procarbazine; D007265:Inhibins; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone