Gonadal damage from chemotherapy and radiotherapy

Abstract

Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men and women. 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 become permanently infertile. 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 in 80% after 5 years. There is also evidence of Leydig cell impairment in a proportion of these men, although the clinical significance of this is not clear. The germinal epithelium is very sensitive to radiation-induced damage, with changes to spermatogonia occurring following as little as 0.1 Gy and permanent infertility after fractionated doses of 2 Gy and above. Cytotoxic-induced premature ovarian failure is age- and drug-dependent and ensues in approximately half of women treated with procarbazine-containing chemotherapy for lymphomas. High-dose chemotherapy, total body irradiation, and irradiation at an ovarian dose above 6 Gy usually result in permanent ovarian failure. The course of ovarian function after chemotherapy is variable, and late recovery occurs in some patients. Several methods of preserving gonadal function during potentially sterilizing treatment have been considered. Currently, sperm banking remains the only proven method in men, although hormonal manipulation to enhance the recovery of spermatogenesis and cryopreservation of testicular germ cells are possibilities for the future. Transposition of the ovaries to allow better shielding during radiotherapy is of use in some women, and the prospect of cryopreservation and reimplantation of ovarian tissue is promising.