Effect of childhood cancer treatment on fertility markers in adult male long-term survivors.
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.
van Casteren
Niels J
NJ
Department of Urology, Section of Andrology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
van der Linden
Geert H M
GH
Hakvoort-Cammel
Friederike G A J
FG
Hählen
Karel
K
Dohle
Gert R
GR
van den Heuvel-Eibrink
Marry M
MM
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
D015415:Biomarkers; C422364:inhibin B; D011344:Procarbazine; D007265:Inhibins; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone