Combination chemotherapy that includes an alkylating agent and procarbazine causes severe damage to the testicular germinal epithelium.[15,16,17,18,19] Azoospermia occurred less frequently in adults following treatment with two, rather than six, cycles of MOPP (mechlorethamine, vincristine [Oncovin], procarbazine, prednisone). Elevation of the basal follicle-stimulating hormone (FSH) level, reflecting impaired spermatogenesis, was less frequent among patients receiving two courses of OPPA (vincristine, procarbazine, prednisone, doxorubicin) than among those who received two courses of OPPA in combination with two or more courses of COPP (cyclophosphamide, vincristine, procarbazine and prednisone).
Most studies suggest that procarbazine contributes significantly to the testicular toxicity of combination chemotherapy regimens. The combination of doxorubicin, bleomycin, vinblastine, and dacarbazine produced oligospermia or azoospermia in adults frequently during the course of treatment. However, recovery of spermatogenesis occurred after treatment was completed, in contrast to the experience reported following treatment with MOPP. Most studies suggested that prepubertal males were not at lower risk for chemotherapy-induced testicular damage than were postpubertal patients.[16,23,24,25]
Male survivors of non-Hodgkin lymphoma who underwent pelvic radiation therapy and received a cumulative cyclophosphamide dose greater than 9.5 g/m2 were at increased risk for failure to recover spermatogenesis; in survivors of Ewing and soft tissue sarcoma, treatment with a cumulative cyclophosphamide dose greater than 7.5 g/m2 was correlated with persistent oligospermia or azoospermia. Spermatogenesis was present in 67% of 15 men who received 200 mg/kg of cyclophosphamide prior to undergoing bone marrow transplantation (BMT) for aplastic anemia. Cyclophosphamide doses exceeding 7.5 g/m2 and ifosfamide doses exceeding 60 g/m2 produced oligospermia or azoospermia in most exposed individuals.[28,29,30]
The majority of postpubertal women who receive TBI prior to BMT develop amenorrhea. Recovery of normal ovarian function occurred in only 9 of 144 patients in one series and was highly correlated with age at irradiation in patients younger than 25 years. In a series restricted to patients who were prepubertal at the time of BMT, 44% (7 of 16) had clinical and biochemical evidence of ovarian failure.
The frequency of ovarian failure following abdominal radiation therapy is related to both the age of the woman at the time of irradiation and the radiation therapy dose received by the ovaries. Whole-abdomen irradiation produces severe ovarian damage. Seventy-one percent of women in one series failed to enter puberty and 26% had premature menopause following whole-abdominal radiation therapy doses of 2,000 cGy to 3,000 cGy. Other studies reported similar results in women treated with whole-abdomen irradiation  or craniospinal irradiation [35,36] during childhood.
Ovarian function may be impaired following treatment with combination chemotherapy that includes an alkylating agent and procarbazine such as MOPP; MVPP (nitrogen mustard [mechlorethamine], vinblastine, procarbazine, and prednisone); ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone); MDP (doxorubicin, prednisone, procarbazine, vincristine, and cyclophosphamide); or the combination of COP (cyclophosphamide, vincristine, and procarbazine) with ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine). Amenorrhea was reported in 11% after MOPP (2 of 18 girls treated at age 2 to 15 years), 31% after MDP (10 of 31 girls treated at age 9.0 to 15.2 years), and 13% after ChIVPP (3 of 23 girls treated at age 6.1 to 20.0 years),[15,37,38] but in 0% after COP/ABVD (0 of 17 girls treated at age 4 to 20 years).