Chemotherapy affecting testicular function

In general, Leydig cell function is preserved, but germ cell failure is common in men treated with high cumulative doses of cyclophosphamide (7,500 mg/m2 or more) and more than 3 months of combination alkylating agent therapy.

Most studies suggest that prepubertal males are not at lower risk of chemotherapy-induced testicular damage than are postpubertal patients.[17-20]

Cyclophosphamide:

Cyclophosphamide:

Male survivors of non-Hodgkin lymphoma who received a cumulative cyclophosphamide dose of greater than 9.5 g/m2 and underwent pelvic radiation therapy were at increased risk of failure to recover spermatogenesis.[21]

Cyclophosphamide:

In survivors of Ewing sarcoma and soft tissue sarcoma, treatment with a cumulative cyclophosphamide dose of greater than 7.5 g/m2 was correlated with persistent oligospermia or azoospermia.[22]

Cyclophosphamide:

Cyclophosphamide doses exceeding 7.5 g/m2 and ifosfamide doses exceeding 60 g/m2 produced oligospermia or azoospermia in most exposed individuals.[23-25]

Cyclophosphamide:

A small cohort study reported normal semen quality in adult long-term survivors of childhood ALL treated with 0 to 10 g/m2 of cyclophosphamide and cranial irradiation, whereas no spermatozoa were detected in semen samples from survivors treated with more than 20 g/m2 of cyclophosphamide.[26]

Cyclophosphamide:

Treatment with a cyclophosphamide equivalent dose of less than 4 g/m2 results in infrequent azoospermia or oligospermia. Approximately 89% of 31 men treated were normospermic.[27]

Cyclophosphamide:

Spermatogenesis was present in 67% of 15 men who received 200 mg/kg of cyclophosphamide before undergoing HSCT for aplastic anemia.[28]

Dacarbazine:

Dacarbazine:

The combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) frequently produced oligospermia or azoospermia in adults during the course of treatment. However, recovery of spermatogenesis occurred after treatment was completed, which is in contrast to the experience reported after treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP).[29]

Alkylating agent plus procarbazine:

Alkylating agent plus procarbazine:

Most studies suggest that combination chemotherapy with an alkylating agent and procarbazine causes severe damage to the testicular germinal epithelium that is irreversible at high cumulative doses.[17,30-33]

Alkylating agent plus procarbazine:

Azoospermia occurred less frequently in adults after treatment with two, rather than six, cycles of MOPP.[34]

Alkylating agent plus procarbazine:

Elevation of the basal follicle-stimulating hormone (FSH) level, which may reflect impaired spermatogenesis, was less frequent among patients who received two courses of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) than among those who received two courses of OPPA in combination with two or more courses of cyclophosphamide, vincristine, procarbazine and prednisone (COPP).[35]

Alkylating agents plus low-dose cranial radiation:

Alkylating agents plus low-dose cranial radiation:

In a cross-sectional study that included male adult survivors of pediatric ALL who had received alkylating agent chemotherapy with or without cranial radiation, St. Jude Children's Research Hospital investigators demonstrated that cranial radiation at doses lower than 26 Gy has no demonstrable independent effect on spermatogenesis.[36]