Cancer treatment and the ovary: the effects of chemotherapy and radiation.
ABSTRACT Certain chemotherapeutic drugs ("alkylators") and radiation therapy are toxic to the ovaries, leading to both loss of sex steroid hormone production and infertility. Higher doses and older age at treatment are both associated with greater damage. Even patients with spontaneous menstrual cycles have evidence of decreased ovarian potential. Adolescents who are treated for cancer with these agents should be counseled about future fertility risks.
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ABSTRACT: Seventy percent of children with cancer survive. Radiation and chemotherapy may, however, impair ovarian function. The aim of this population-based study was to achieve a comprehensive knowledge of the degree of ovarian damage. Ovarian function was evaluated in 100 childhood cancer survivors and 21 controls of similar age. Menstrual cycle pattern was recorded, and strictly timed ovarian sonography and hormonal assessment were performed. The median age of the survivors was 5.4 yr (range, 0.1-15.3) at the time of diagnosis and 25.7 yr (18.5-44.4) at study entry. Seventeen survivors with premature ovarian failure had follicle-depleted or nondetectable ovaries, elevated FSH and LH, and immeasurable inhibin B. Thirteen survivors used oral contraception. Survivors with spontaneous menstrual cycles (n = 70) had smaller ovarian volume per ovary than controls (median, 4.8 vs. 6.8 cm(3); P < 0.001) and a lower number of antral follicles per ovary (median, 7.5 vs. 11; P < 0.001). Further, they had lower inhibin B levels than controls (median, 94 vs. 111 pg/ml; P = 0.03) and higher estradiol levels (median, 0.12 vs. 0.08 pM; P = 0.04). Multiple linear regression analysis was performed to predict the total antral follicle number per ovary, and it showed a reduced number with ovarian irradiation (beta = -0.40, P < 0.001), alkylating chemotherapy (beta = -0.25, P = 0.01), older age at diagnosis (beta = -0.25, P = 0.01), and longer time period off treatment (beta = -0.19, P = 0.044). One in every six female survivors may develop premature ovarian failure. In survivors with spontaneous menstrual cycles, the results indicate a diminished ovarian reserve. Consequently, cessation of fertility may occur much earlier than anticipated. Adult survivors with spontaneous cycles should be informed hereof to plan childbearing.Journal of Clinical Endocrinology & Metabolism 11/2003; 88(11):5307-14. · 6.43 Impact Factor
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ABSTRACT: The ovaries of children with abdominal tumours were studied in 12 autopsy specimens. Ovaries from 25 children who died in accidents or after a short acute disease served as controls. All ovaries from normal children showed follicle growth, but follicle development was inhibited in 67% of the children with abdominal tumours. The effect of treatment with cytotoxic drugs and/or abdominal irradiation on ovarian morphology was investigated. Normal ovaries were found only in children who had received no chemotherapy or a short course. All patients who had been treated with radiation therapy either alone or in conjunction with chemotherapy had severely damaged ovaries: follicle growth was inhibited in all cases, and the number of small non-growing follicles was markedly reduced in most. It is argued that abdominal irradiation might impair follicle development as well as destroy small follicles.British Journal of Cancer 09/1977; 36(2):269-75. · 5.08 Impact Factor
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ABSTRACT: We determined the best model available for natural follicle decline in healthy women and used this to calculate the radiosensitivity of the human oocyte. Ovarian failure was diagnosed in six patients with a median age of 13.2 years (range 12.5-16.0) who were treated with total body irradiation (14.4 Gy) at 11.5 years of age (4.9-15.1). We previously estimated the dose of radiation required to destroy 50% of the oocytes (LD(50)) to be <4 Gy. This estimate is an oversimplification, because decay represents an instantaneous rate of temporal change based upon the remaining population pool, expressed as a differential equation: dy/dx = -y[0.0595 + 3716/(11780 + y)], with initial value y(0) = 701 200. Solving the differential equation, we have estimated the number of follicles left after irradiation given as sol(51 - s + r), where r equals age at treatment, s equals age at diagnosis of ovarian failure, and 51 years is the average age of menopause. The surviving fraction of oocytes as a percentage is 100 times this value divided by sol(r). The mean surviving fraction for the six cases is 0.66%. We obtain a function, g(z), which decreases in value from 100% at zero dosage to mean value at dosage z = 14.4 Gy. We have g(z) = 10(mx+c), where c = log(10)100 = 2, and m = [log(10)(0.66) - c]/14.4. Solving g(z) = 50 gives an LD(50) of 1.99. Based on new data and a revised mathematical model of natural oocyte decline, we have determined the surviving fraction of oocytes following irradiation and estimate the LD(50) of the human oocyte to be <2 Gy.Human Reproduction 01/2003; 18(1):117-21. · 4.67 Impact Factor