Ovarian failure may be a result of chemotherapy or radiation therapy for malignancy, or may result from extensive ovarian surgery. The risk of post-chemotherapy ovarian failure depends upon the agents administered, the dosage, and the duration. The ovaries of younger women appear to be less sensitive to the toxic effects of chemotherapy.
After treatment with methotrexate or anthracycline-based chemotherapy, 30% of women with early-stage breast cancer are amenorrheic one year after chemotherapy. Although amenorrhea was most likely to occur in older women, 28% of women under 35 have persistent menstrual abnormalities. The ovarian toxicity of cyclophosphamide and procarbazine is well known. Studies in mice have shown that the number of primordial follicles lost with cyclophosphamide therapy is in direct proportion to the dose given. In women with lupus who are treated with cyclophosphamide pulse therapy, POF is seen in 100% of those over age 30, in 50% of those between 20 and 30 years old, and in 13% of those younger than 20.
Because cells that are actively dividing are more sensitive to the cytotoxic effects of alkylating agents, it was hypothesized that suppression of pituitary FSH secretion may result in less damage to ovarian follicles. Recently it has been shown that concurrent treatment with a GnRH agonist can prevent ovarian failure in women undergoing cyclophosphamide therapy for lupus. Similarly, a group of women with Hodgkin's disease and non-Hodgkin's lymphoma treated with MOPP/ABV(D) combination chemotherapy was treated concomitantly with a GnRH agonist. Fifteen out of 16 patients resumed normal menses after therapy, as compared to only seven out of 18 in a similar group not treated with GnRH agonist.
Total body irradiation with an ovarian dose above 6 Gy usually results in permanent ovarian failure. An ovarian dose of 4 Gy may cause ovarian failure in 30% of young women, but in virtually all women over the age of 40. When pelvic irradiation is required, laparoscopic lateral transposition of the ovaries has been shown to often decrease the risk of ovarian failure. However, in a group of women who received pelvic irradiation following radical hysterectomy for cervical cancer, ovarian failure occurred in 49% of the women despite ovarian transposition. In women who did not receive postoperative radiation, 98% retained ovarian function, with menopause occurring at a mean age of 46. In a group of long-term survivors of childhood cancer treated with irradiation, 68% of those who had both ovaries in the radiotherapy field had POF. In those whose ovaries were at the edge of the field, 14% had POF, while none of those whose ovaries were outside the field had POF. Temporary amenorrhea and elevated serum gonadotropin levels have been shown in some women who undergo radioactive iodine therapy for thyroid cancer.
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