Effect of cancer therapy on pituitary-testicular axis1

Abstract
Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men. Alkylating agents, such as cyclophosphamide and procarbazine, are the most common agents implicated. The vast majority of men receiving procarbazine‐containing regimens for the treatment of lymphomas are rendered permanently infertile. Treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) appears to have a significant advantage in terms of testicular function, with a return to normal fertility in the vast majority of patients. Cisplatin‐based chemotherapy for testicular cancer results in temporary azoospermia in most men with a recovery of spermatogenesis in about 50% after 2 years and 80% after 5 years. There is also evidence of chemotherapy‐induced Leydig cell impairment in a proportion of these men, although this appears to be of no clinical significance in the majority of patients. The germinal epithelium is very sensitive to radiation‐induced damage with changes to spermatogonia following as little as 0.1 Gy, and permanent infertility after fractionated doses of 2 Gy and above, whereas clinically significant Leydig cell impairment occurs rarely with doses of less than 20 Gy.