In addition to these alkylating agents, vinblastine, cytarabine, cisplatinum, and procarbazine have also been reported to be gonadotoxic in male and female patients.
Chemotherapy regimens for the treatment of non-Hodgkin lymphoma are generally less gonadotoxic than those used for Hodgkin lymphoma. The addition of adjuvant endocrine therapy in patients older than 40 years was more likely to result in permanent chemotherapy-related amenorrhea. The effects of chemotherapy on testicular function have also been widely studied in patients with testicular cancer. One review reported that more than half of the patients with testicular germ cell cancer showed impaired spermatogenesis before undergoing cytotoxic treatment. Permanent infertility is ultimately defined by dose of cisplatin in these patients. At doses lower than 400 mg/m2, long-term effects on endocrine function and sperm production are unlikely to occur. Higher doses would be expected to cause long-term endocrine-gonadal dysfunction.
Although chemotherapy causes ovarian damage, there appears to be no risk of toxicity to future offspring of women treated with these agents before pregnancy.
When the testes are exposed to radiation, sperm count begins to decrease and, depending on the dosage, temporary or permanent sterility may result. Men who receive radiation to the abdominal or pelvic region may still regain partial or full sperm production, depending on the extent of injury to the testes. Unlike the germinal epithelium, Leydig cell function may be more prone to damage from irradiation in prepubertal life than in adulthood. Testicular radiation with doses higher than 20 Gy is associated with Leydig cell dysfunction in prepubertal boys, while Leydig cell function is usually preserved with doses of as much as 30 Gy in sexually mature males. Exposing the testes to ionizing radiation at a dose lower than 6 Gy causes disturbances of spermatogenesis and altered spermatocytes with recovery periods dependent on dose; doses higher than 6 Gy cause permanent infertility by killing off all stem cells.
For patients with testicular germ cell cancer, using modern radiation techniques (radiation doses <30 Gy to the para-aortic field) and testis shielding providing testis scatter radiation (<30 Gy), radiation-induced impairment of fertility is very unlikely. Sperm counts are typically lowest at 4 to 6 months posttreatment; return to pretreatment levels usually occurs in 10 to 24 months, with longer periods required for recovery after higher doses. Total-body irradiation (TBI) as a conditioning regimen for stem cell transplantation causes permanent gonadal failure in approximately 80% of men. For men, gonadal toxicity can be evidenced by the following three measurements:
- Testicular biopsy.
- Serum hormone assays (levels).
- Semen analysis.