Premature menopause in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study Journal Article


Authors: Sklar, C. A.; Mertens, A. C.; Mitby, P.; Whitton, J.; Stovall, M.; Kasper, C.; Mulder, J.; Green, D.; Nicholson, H. S.; Yasui, Y.; Robison, L. L.
Article Title: Premature menopause in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study
Abstract: Background: Childhood cancer survivors who retain ovarian function after completing cancer treatment are at increased risk of developing premature menopause, defined as cessation of menses before age 40 years. However, published data pertaining to the risk and frequency of premature menopause are limited. Methods: We assessed the incidence of and risk factors for premature menopause in 2819 survivors of childhood cancer who were older than 18 years and were participants in the multicenter Childhood Cancer Survivor Study (CCSS). The comparison group was 1065 female siblings of participants in the CCSS. A multiple Poisson regression model was constructed to determine risk factors for nonsurgical premature menopause. All statistical tests were two-sided. Results: A total of 126 childhood cancer survivors and 33 control siblings developed premature menopause. Of these women, 61 survivors (48%) and 31 siblings (94%) had surgically induced menopause (rate ratio [RR] = 0.8, 95% confidence interval [CI] = 0.52 to 1.23). However, the cumulative incidence of nonsurgical premature menopause was higher for survivors than for siblings (8% versus 0.8%; RR = 13.21, 95% CI = 3.26 to 53.51; P <.001). A multiple Poisson regression model showed that risk factors for nonsurgical premature menopause included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score (based on number of alkylating agents and cumulative dose), and a diagnosis of Hodgkin lymphoma. For survivors who were treated with alkylating agents plus abdominopelvic radiation, the cumulative incidence of nonsurgical premature menopause approached 30%. Conclusions: The results of this study will facilitate counseling current survivors about their future risk of premature menopause and aid in designing new regimens that seek to diminish late ovarian toxicity. © 2006 Oxford University Press.
Keywords: adult; controlled study; middle aged; antibiotic agent; major clinical study; antineoplastic agents; chemotherapy, adjuvant; radiotherapy, adjuvant; neoplasms; cohort studies; radiotherapy dosage; incidence; odds ratio; risk factors; alkylating agent; cyclophosphamide; steroid; cancer therapy; risk factor; chlormethine; childhood cancer; high risk patient; hodgkin disease; radiation exposure; age; cancer survivor; questionnaires; survivors; confidence interval; poisson distribution; ovary; statistical analysis; antineoplastic agents, alkylating; platinum derivative; sibling; dna topoisomerase inhibitor; statistical model; patient counseling; antimetabolite; reproductive toxicity; early menopause; alkaloid; pituitary gland; ovary function; multicenter studies; menopause, premature
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 98
Issue: 13
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2006-07-05
Start Page: 890
End Page: 896
Language: English
DOI: 10.1093/jnci/djj243
PUBMED: 16818852
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 140" - "Export Date: 4 June 2012" - "CODEN: JNCIA" - "Source: Scopus"
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  1. Charles A Sklar
    303 Sklar