Endocrinology and Metabolism Clinics of North America
GONADAL DAMAGE FROM CHEMOTHERAPY AND RADIOTHERAPY
Section snippets
Chemotherapy
Spitz and co-workers83 first described testicular damage from cytotoxic drugs in humans in 1948 when they found azoospermia in 27 of 30 men at autopsy following treatment with nitrogen mustard. Many other drugs, particularly alkylating agents, have subsequently been shown to be gonadotoxic. The agents most commonly implicated are listed in Table 1. The germinal epithelium is far more sensitive to the effects of cytotoxic drugs than are the Leydig cells. Although complete azoospermia is not
PREVENTION OF TESTICULAR DAMAGE
The deleterious effects of chemotherapy and radiotherapy on germinal epithelial function have initiated a search for possible strategies to preserve fertility in men undergoing therapy. Cryostorage of semen has become standard practice and should be offered to all men before they undergo potentially sterilizing therapy. Although improvements in the techniques used to store semen72 and advances in the field of assisted reproduction such as intracytoplasmic sperm injection (ICSI) have increased
Chemotherapy
The gonadotoxic effects of chemotherapy in women were first reported by Louis and co-workers48 in patients treated with busulfan for chronic myeloid leukemia. Subsequently, several drugs have been implicated in the development of ovarian dysfunction.
The effects of cyclophosphamide used in the treatment of breast cancer, renal disorders, and rheumatologic conditions have been widely studied. Ovarian damage has been shown to be dose-dependent and age-dependent,5, 43 with progressively smaller
PREVENTION OF OVARIAN FAILURE
Because of the consequences of ovarian failure in young women, several strategies have been tried in an attempt to reduce the gonadotoxic effect of cancer treatment. Transposition of the ovaries before radiotherapy can reduce the dose of irradiation to the ovaries to approximately 10% of the given dose during pelvic radiotherapy.33, 59, 66 Although this has been shown to reduce the incidence of ovarian dysfunction,66 the routine use of ovarian transposition in patients with Hodgkin's disease
SUMMARY
Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men and women. Alkylating agents such as cyclophosphamide and procarbazine are the most common agents implicated. The vast majority of men receiving procarbazine-containing regimens for the treatment of lymphomas become permanently infertile. Cisplatin-based chemotherapy for testicular cancer results in temporary azoospermia in most men, with a recovery of spermatogenesis in about 50% after 2
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Address reprint requests to Stephen Shalet, MD, Department of Endocrinology, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, United Kingdom
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Department of Endocrinology, Christie Hospital NHS Trust, Manchester, United Kingdom