Spermatogenesis after cancer treatment: damage and recovery.
Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men, and alkylating agents are the most common agents implicated. The vast majority of men receiving procarbazine-containing regimens for the treatment of lymphomas are rendered permanently infertile, whereas treatment with doxorubicin hydrochloride (Adriamycin), bleomycin, vinblastine, and dacarbazine appears to have a significant advantage, 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% of the patients after 2 years and 80% after 5 years. The germinal epithelium is very sensitive to radiation-induced damage, with changes to spermatogonia following as little as 0.2 Gy. Testicular doses of less than 0.2 Gy had no significant effect on FSH levels or sperm counts, whereas doses between 0.2 and 0.7 Gy caused a transient dose-dependent increase in FSH and reduction in sperm concentration, with a return to normal values within 12-24 months. No radiation dose threshold has been defined above which permanent azoospermia is inevitable; however, doses of 1.2 Gy and above are likely to be associated with a reduced risk of recovery of spermatogenesis; the time to recovery, if it is to occur, is also likely to be dose dependent.
Howell
S J
SJ
Department of Endocrinology, Christie Hospital NHS Trust, Withington, Manchester, UK M20 4BX.
Shalet
S M
SM
D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004249:DNA Damage; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D007248:Infertility, Male / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D011832:Radiation Injuries; D013091:Spermatogenesis; D013736:Testicular Neoplasms / Q000188:drug therapy; D014916:Whole-Body Irradiation / Q000009:adverse effects
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide