Journal Article

Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort

Robison, Leslie L., Green, Daniel M., Clark, Karen L., Brooke, Russell J., Srivastava, Deo Kumar, Farr, Jonathan B., Sklar, Charles A., Krasin, Matthew J., Fernandez-Pineda, Israel, Hudson, Melissa M., Ness, Kirsten K., Barnes, Nicole, Pui, Ching-Hon, Chemaitilly, Wassim, Yasui, Yutaka, Li, Zhenghong, Wilson, Carmen L., Metzger, Monika, Klosky, James L., Kaste, Sue C., Bishop, Michael W.

2017

Overview

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.We report on the prevalence, risk factors, and consequences on general health of premature ovarian insufficiency in a cohort of 921 long-term survivors of childhood cancers.

• Publisher: Endocrine Society,Oxford University Press
• Subject: Adolescent / Adult / Alkylating agents / Amenorrhea / Antineoplastic Agents, Alkylating - adverse effects / Antineoplastic Agents, Alkylating - therapeutic use / Body Mass Index / Bone mass / Bone mineral density / Cancer / Cardiovascular diseases / Childhood / Children / Clinical s / Cohort Studies / Cross-Sectional Studies / Cyclophosphamide / Diagnosis / Drug dosages / Female / Fertility / Follicle-stimulating hormone / Health risk assessment / Humans / Middle Aged / Neoplasms - epidemiology / Neoplasms - therapy / Osteoporosis - epidemiology / Osteoporosis - etiology / Ovarian cancer / Ovaries / Ovary - radiation effects / Parity / Prevalence / Primary Ovarian Insufficiency - epidemiology / Primary Ovarian Insufficiency - etiology / Radiation Dosage / Radiation therapy / Radiotherapy - adverse effects / Risk Factors / Sex hormones / Survivors / Tennessee - epidemiology / Young Adult