Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort
Premature Ovarian Insufficiency in Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort
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DOI：
10.1210/jc.2016-3723
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发表时间：
2017-07-01
影响因子：
5.8
通讯作者：
Sklar, Charles A.
中科院分区：
文献类型：
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作者：
Chemaitilly, Wassim;Li, Zhenghong;Sklar, Charles A.
背景：关于儿童癌症幸存者卵巢功能不全的长期随访数据有限。目的：描述卵巢功能不全的患病率、其危险因素和相关的长期不良健康结果。设计：横断面。背景：圣犹大终身队列研究，在三级护理中心建立的队列研究。患者：921名参与者(中位年龄，31.7岁)在癌症诊断后的中位数24.0年进行评估。主要观察指标：卵巢功能不全的定义是40岁以前的持续性闭经和卵泡刺激素水平>；30IU/L。多变量COX回归用于研究人口统计学或治疗相关危险因素与POI之间的关系。多变量Logistic回归用于研究POI与心血管疾病标志物、骨密度(BMD)和脆弱程度之间的关系。使用验证的环磷酰胺当量剂量(CED)对烷化剂的暴露进行量化。结果：POI的患病率为10.9%。POI的独立危险因素包括任何剂量的卵巢放疗和CED>；=8000 mg/m(2)。在圣犹大终身队列评估时，体重指数<gt；=30 kg/m(2)的患者诊断为POI的可能性较小。低骨密度和骨质疏松症与POI独立相关。结论：大剂量烷化剂和任何剂量的卵巢放疗均与POI有关。只要可行，最高风险的患者应该保留生育能力。POI导致儿童癌症幸存者的一般健康结果较差；需要进一步研究性激素替代在改善此类结果中的作用。
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/m(2). Patients with a body mass index >= 30 kg/m(2) 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.