Chemaitilly Wassim, Li Zhenghong, Krasin Matthew J, Brooke Russell J, Wilson Carmen L, Green Daniel M, Klosky James L, Barnes Nicole, Clark Karen L, Farr Jonathan B, Fernandez-Pineda Israel, Bishop Michael W, Metzger Monika, Pui Ching-Hon, Kaste Sue C, Ness Kirsten K, Srivastava Deo Kumar, Robison Leslie L, Hudson Melissa M, Yasui Yutaka, Sklar Charles A
Department of Pediatric Medicine-Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
J Clin Endocrinol Metab. 2017 Jul 1;102(7):2242-2250. doi: 10.1210/jc.2016-3723.
Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited.
To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes.
Cross-sectional.
The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center.
Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis.
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).
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.
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.
儿童癌症幸存者中卵巢早衰（POI）的长期随访数据有限。
描述POI的患病率、危险因素及相关的长期不良健康结局。
横断面研究。
圣裘德终身队列研究，这是一家三级医疗中心的既定队列。
921名参与者（中位年龄31.7岁）在癌症诊断后中位24.0年接受评估。
POI定义为40岁前持续性闭经且促卵泡生成素水平>30 IU/L。采用多变量Cox回归研究人口统计学或治疗相关危险因素与POI之间的关联。采用多变量逻辑回归研究POI与心血管疾病、骨密度（BMD）和衰弱标志物之间的关联。使用经过验证的环磷酰胺等效剂量（CED）对烷化剂暴露进行量化。
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/m²。在圣裘德终身队列评估时体重指数≥30 kg/m²的患者被诊断为POI的可能性较小。低BMD和衰弱与POI独立相关。
高剂量烷化剂和任何剂量的卵巢放疗与POI相关。只要可行，应向风险最高的患者提供生育力保存。POI导致儿童癌症幸存者总体健康结局不佳；需要进一步研究来调查性激素替代在改善这些结局中的作用。
