Sexuality and Reproductive Issues (PDQ®): Supportive care - Health Professional Information [NCI] - Fertility Issues
Adjuvant radiation therapy and/or chemotherapy introduce higher risks of infertility in patients with cancer. Sterility from these therapies may be temporary or permanent. The occurrence of this toxicity is related to a number of factors including the individual's gender, age at the time of treatment, type of therapeutic agent, radiation field, total dose, single versus multiple agents, and length of time since treatment.
When treatment-related or disease-related dysfunction is a possibility, every effort should be made to provide adequate information and education on reproduction and fertility. Conveying such information can be complicated, especially in younger pediatric cancer patients. Children may be too young to comprehend the implications of treatment on fertility. Additionally, in some instances, parents may decide to shelter children from such discussions. Existing literature suggests that only about half of men and women of child-bearing age receive the information they need from their health care providers about cancer-related infertility at the time of diagnosis and treatment planning. This lack of information is one of the most common reasons men give for failing to bank sperm. To address this issue, a computerized interactive educational tool for patients, families, and physicians called Banking on Fatherhood after Cancer is under development and will be viewable on CD-ROM or over the Internet.
Survivors of childhood cancer are at risk for a spectrum of neuroendocrine abnormalities, primarily due to the effect of radiation therapy on the hypothalamus. Essentially all of the hypothalamic-pituitary axes are at risk.[1,2,3] The six anterior pituitary hormones and their major hypothalamic regulatory factors are outlined in Table 10.
Table 10. Anterior Pituitary Hormones and Major Hypothalamic Regulatory Factors
(-) = inhibitory; (+) = stimulatory.
With regard to chemotherapy, the extent of damage to a patient's fertility depends on the agent administered, the doses received, and the patient's age at the time of treatment. Age is an important factor, and the possibility of gonadal recovery improves with the length of time off chemotherapy. The germinal epithelium of the adult testis is more susceptible to damage than that of the prepubertal testis. The evidence to date (largely from adjuvant studies) suggests that patients older than 35 to 40 years are most susceptible to the ovarian effects of chemotherapy. The ovaries of younger women can tolerate greater doses. Predicting the outcome for any individual patient is difficult, as the course of ovarian functioning following chemotherapy is variable. Relative risk of ovarian failure and testicular damage from cytotoxic agents has been studied, and the alkylating agents have subsequently been shown to be damaging to fertility. The following agents have been shown to be gonadotoxic: busulfan, melphalan, cyclophosphamide, nitrosoureas, cisplatin, chlorambucil, mustine, carmustine, lomustine, cytarabine, ifosfamide, and procarbazine.[3,5,6,7,8] 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.