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JNCI Journal of the National Cancer Institute 2006 98(13):890-896; doi:10.1093/jnci/djj243
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© The Author 2006. Published by Oxford University Press.

ARTICLE

Premature Menopause in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Charles A. Sklar, Ann C. Mertens, Pauline Mitby, John Whitton, Marilyn Stovall, Catherine Kasper, Jean Mulder, Daniel Green, H. Stacy Nicholson, Yutaka Yasui, Leslie L. Robison

Affiliations of authors: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY (CAS); Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN (ACM, PM); Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA (JW); Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (MS, CK); Department of Medicine, Brigham and Women's Hospital, Boston, MA (JM); Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, NY (DG); Department of Pediatrics, Oregon Health Sciences University, Portland, OR (HSN); Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada (YY); Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN (LLR)

Correspondence to: Charles A. Sklar, MD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021 (e-mail: sklarc{at}mskcc.org).

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.



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Editorial about this Article

Premature Ovarian Failure in Cancer Survivors: New Insights, Looming Concerns
Wendy Y. Chen and JoAnn E. Manson
J Natl Cancer Inst 2006 98: 880-881. [Extract] [Full Text] [PDF]



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