Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study Journal Article


Authors: Levine, J. M.; Whitton, J. A.; Ginsberg, J. P.; Green, D. M.; Leisenring, W. M.; Stovall, M.; Robison, L. L.; Armstrong, G. T.; Sklar, C. A.
Article Title: Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
Abstract: BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact on reproduction remain poorly defined. METHODS: The menopausal status of 2930 survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20 years]) who were aged > 18 years at the time of the current study (median age, 35 years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as the cessation of menses ≥6 months in duration occurring 5 years after diagnosis and before age 40 that was not due to pregnancy, surgery, or medications. Among survivors, multivariable logistic regression identified risk factors for NSPM. Pregnancy and live birth rates were compared between survivors with and without NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years [range, 16-40 years]), with a prevalence at age 40 years of 9.1% (95% confidence interval [95% CI], 4.9%-17.2%); the odds ratio (OR) was 10.5 (95% CI, 4.2-26.3) compared with siblings. Independent risk factors included exposure to a procarbazine dose ≥4000 mg/m2 (OR, 8.96 [95% CI, 5.02-16.00]), any dose of ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95% CI, 1.33-5.61] and OvRT ≥ 500 cGy: OR, 8.02 [95% CI, 2.81-22.85]; referent RT, 0), and receipt of a stem cell transplantation (OR, 6.35; 95% CI, 1.19-33.93). Compared with survivors without NSPM, those who developed NSPM were less likely to ever be pregnant (rate ratio, 0.49; 95% CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95% CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood cancer are at risk of NSPM associated with lower rates of live birth in their 30s. Those at risk should consider fertility preservation if they anticipate delaying childbearing. Cancer 2018;124:1044-52. © 2018 American Cancer Society. © 2018 American Cancer Society
Keywords: adolescent; adult; child; controlled study; major clinical study; cancer radiotherapy; radiation dose; follow up; prevalence; cohort analysis; odds ratio; alkylating agent; cyclophosphamide; stem cell transplantation; risk factor; procarbazine; childhood cancer; radiation exposure; late effects; cancer survivor; confidence interval; ovary; clinical study; survivorship; pregnancy; sibling; logistic regression analysis; pregnancy outcome; reproduction; premature menopause; live birth; early menopause; birth rate; reproductive outcomes; human; female; priority journal; article; nonsurgical premature menopause
Journal Title: Cancer
Volume: 124
Issue: 5
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2018-03-01
Start Page: 1044
End Page: 1052
Language: English
DOI: 10.1002/cncr.31121
PROVIDER: scopus
PMCID: PMC5869021
PUBMED: 29338081
DOI/URL:
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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MSK Authors
  1. Charles A Sklar
    283 Sklar