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Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Reproductive System


A French cohort study of 1,109 female survivors of childhood solid cancer identified the following as risk factors for nonsurgical menopause: exposure to and dose of alkylating agents, especially during adolescence; radiation dose to the ovaries; and oophorectomy. Women treated with alkylating agents after the onset of puberty, either alone (RR, 9; 95% CI, 2.7-28, P = .0003) or associated with even a low dose of radiation to the ovaries (RR, 29; 95% CI, 8-108, P < .0001), had the highest risk ratio for nonsurgical menopause. Exposure to unilateral oophorectomy was associated with a 7-year-earlier age at menopause. The overall rate of nonsurgical menopause by age 40 years was only 2.1% and substantially lower than the CCSS and European Organization for Research and Treatment of Cancer cohort studies that include survivors of hematological malignancies.[50]


Fertility was evaluated among the 6,224 male CCSS participants aged 15 to 44 years who were not surgically sterile. They were less likely to sire a pregnancy than siblings (hazard ratio [HR] 0.56; 95% CI, 0.49-0.63). Among survivors, the HR of siring a pregnancy was decreased by radiation therapy greater than 750 cGy to the testes (HR, 0.12; 95% CI, 0.02-0.64), higher summed alkylating agent dose score or treatment with cyclophosphamide (third tertile - HR, 0.42; 95% CI, 0.31-0.57) or procarbazine (second tertile - HR, 0.48; 95% CI, 0.26-0.87; third tertile - HR, 0.17; 95% CI, 0.07-0.41). The HR of siring a pregnancy was inversely related to the summed alkylating agent dose score (P -value for linear trend = <.001). Those who had a summed alkylating agent dose score of 2 (HR, 0.67; 95% CI, 0.51-0.88; P = .004), 3 (HR, 0.48; 95% CI, 0.36-0.65; P <.001), 4 (HR, 0.34; 95% CI, 0.22-0.52; P <.001), 5 (HR, 0.38; 95% CI, 0.22-0.66; P <.001), or 6 to 11 (HR, 0.16; 95% CI, 0.08-0.32; P <.001) were also less likely to ever sire a pregnancy compared with those who did not receive any alkylating agents. Compared with siblings, the HR for ever siring a pregnancy for survivors who had an alkylating agent dose score of 0 and a hypothalamic/pituitary radiation dose of 0 cGy and a testes radiation dose of 0 cGy was 0.91 (95% CI, 0.73-1.14; P = .41).[51]

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