Gonadotoxicity of cancer therapies in pediatric and reproductive-age males

Abstract

The male reproductive tract is highly susceptible to the toxic effects of chemotherapy and radiation therapy, which may damage the testes directly as well as disrupt the endocrine axis by altering Leydig cell function. Approximately 1 in every 5,000 young males is at risk for infertility due to their cancer treatment. Both prepubertal and pubertal testes are vulnerable to cytotoxic agents used in cancer therapy, and the alkylating agents often used to treat pediatric cancers are highly gonadotoxic. Alkylating agents that are known to cause infertility include busulfan, cisplatin, cyclophosphamide, ifosfamide, and procarbazine. With regard to radiation therapy, even very low doses—either due to scatter or from direct irradiation—can cause significant impairment of testicular function. Assessment of the effects of chemotherapy or radiation therapy on testicular maturation and function in male cancer patients is an important part of care and involves pubertal staging, plasma hormone analysis, and semen analysis. It is essential for oncologists to consider the potential impacts of cancer treatment on fertility and provide their patients options to preserve fertility, prior to initiating chemotherapy or radiation therapy.