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Acute Ovarian Failure in the Childhood Cancer Survivor Study

Department of Pediatrics (W.C., C.A.S.), Memorial Sloan-Kettering Cancer, New York, New York 10021; Division of Pediatric Endocrinology (W.C.), New York Presbyterian Hospital, Weill Cornell Medical College, New York, New York 10021; Department of Pediatrics (A.C.M., P.M.), University of Minnesota School of Medicine, Minneapolis, Minnesota 55455; Cancer Prevention Research Program (J.W.), Fred Hutchinson Cancer Research Center, Seattle, Washington 98104; Department of Radiation Physics (M.S.), University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030; Department of Public Health Sciences (Y.Y.), University of Alberta, Edmonton, Alberta, Canada T6G2G3; and Department of Epidemiology and Cancer Control (L.L.R.), St. Jude Children’s Research Hospital, Memphis, Tennessee 38105

Address all correspondence and requests for reprints to: Charles A. Sklar, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021. E-mail: sklarc{at}mskcc.org.

Context: Defined as the loss of ovarian function within 5 yr of diagnosis, acute ovarian failure (AOF) is known to develop in a subset of survivors of pediatric and adolescent cancers. Its precise incidence is unknown, and data concerning its risk factors are limited.

Objective: Our objective was to determine the incidence of and patient/treatment factors associated with AOF in a large cohort of pediatric cancer survivors.

Design and Setting: We conducted a retrospective cohort, multicenter study.

Patients: Female participants from the Childhood Cancer Survivor Study who were greater than 18 yr of age were considered for inclusion. We excluded survivors who received cranial irradiation at doses of more than 3000 cGy, those with hypothalamic/pituitary tumors, and survivors who underwent bilateral oophorectomy. Survivors who reported never menstruating or who had ceased having menses within 5 yr after their cancer diagnosis were considered to have AOF.

Main Outcome: We assessed incidence and risk factors for AOF.

Results: Of a total of 3390 eligible survivors, 215 cases (6.3%) developed AOF. Survivors with AOF were older at diagnosis and more likely to have been diagnosed with Hodgkin’s lymphoma or to have received abdominal or pelvic radiotherapy than survivors without AOF. Among survivors with AOF, 116 (54%) had received at least 1000-cGy ovarian irradiation. In a multivariable logistic regression model, increasing doses of ovarian irradiation, exposure to procarbazine, and exposure to cyclophosphamide at ages 13–20 yr were independent risk factors for AOF.

Conclusions: AOF develops in a small subset of survivors, especially those treated with at least 1000-cGy ovarian radiation. These results will facilitate patient counseling and selection of candidates for newer fertility preservation techniques.

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