Wassim Chemaitilly1,2, Zhenghong Li2, Matthew J Krasin3, Russell J Brooke2, Carmen L Wilson2, Daniel M Green2,4, James L Klosky5, Nicole Barnes1, Karen L Clark1, Jonathan B Farr3, Israel Fernandez-Pineda6, Michael W Bishop4, Monika Metzger4, Ching-Hon Pui4, Sue C Kaste3,4,7, Kirsten K Ness2, Deo Kumar Srivastava8, Leslie L Robison2, Melissa M Hudson2,4, Yutaka Yasui2, Charles A Sklar9. 1. Department of Pediatric Medicine-Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105. 2. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105. 3. Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105. 4. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105. 5. Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105. 6. Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee 38105. 7. Department of Radiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163. 8. Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105. 9. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065.
Abstract
Context: Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited. Objective: To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes. Design: Cross-sectional. Setting: The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center. Patients: Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis. Main Outcome Measure: POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED). Results: The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI. Conclusion: High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes.
Context: Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited. Objective: To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes. Design: Cross-sectional. Setting: The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center. Patients: Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis. Main Outcome Measure: POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED). Results: The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI. Conclusion: High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes.
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