Hormonal approaches to preservation and restoration of male fertility after cancer treatment.

It is important to develop methods to prevent or reverse the sterility caused by chemotherapy or radiation therapy for cancer in men. Using a rat model, we have shown that infertility after testicular exposure to moderate doses of radiation and some chemotherapeutic agents occurs as a result of the inability of spermatogonia to differentiate. There is evidence that this phenomenon also occurs in men. Spermatogenesis and fertility can be restored in rats following treatment with radiation or some chemotherapeutic agents by suppressing testosterone with gonadotropin releasing hormone (GnRH) agonists or antagonists either before or after the cytotoxic insult. However, species differences exist in the testicular response to radiation or GnRH antagonist therapy, so rescue protocols that work in rodents do not work in nonhuman primates. The applicability of this procedure to humans is still largely unknown. In rodents, suppression of testosterone with GnRH analog treatment also appears to enhance the success of spermatogonial transplantation-an option when all stem cells are killed by cytotoxic therapy.