Exposure to endocrine disrupting chemicals is suggested to be responsible for the development or progression of uterine fibroids. However, little is known about risks related to emerging chemicals, such as organophosphate esters (OPEs) and alternative plasticizers (APs). A case-control study was conducted to investigate whether exposures to OPEs, APs, and phthalates, were associated with uterine fibroids in women of reproductive age. For this purpose, the cases (n = 32) and the matching controls (n = 79) were chosen based on the results of gynecologic ultrasonography among premenopausal adult women in Korea and measured for metabolites of several OPEs, APs, and major phthalates. Logistic regression models were employed to assess the associations between chemical exposure and disease status. Factor analysis was conducted for multiple chemical exposure assessments as a secondary analysis. Among OPE metabolites, diphenyl phosphate (DPHP), 2-ethylhexyl phenyl phosphate (EHPHP), and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) were detected in >80% of the subjects. Among APs, metabolites of di-isononyl phthalate (DINP) and di(2-propylheptyl) phthalate (DPrHpP) were detected in >75% of the urine samples. The odds ratios (ORs) of uterine fibroids were significantly higher among the women with higher exposures to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-butoxyethyl) phosphate (TBOEP), di(2-ethylhexyl) terephthalate (DEHTP), DPrHpP, and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH). In addition, urinary concentrations of mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), a sum of five di(2-ethylhexyl) phthalate metabolites (∑5DEHP), and mono(4-methyl-7-hydroxyoctyl) phthalate (OH-MINP) were significantly higher in the cases. In factor analysis, a factor heavily loaded with DPrHpP and DEHP was significantly associated with uterine fibroids, supporting the observation from the single chemical regression model. We found for the first time that several metabolites of OPEs and APs are associated with increased risks of uterine fibroids among pre-menopausal women. Further epidemiological and mechanistic studies are warranted to validate the associations observed in the present study.

建议暴露于破坏内分泌的化学物质是子宫肌瘤发生或发展的原因。但是，对于与新兴化学品（例如有机磷酸酯（OPE）和替代增塑剂（AP））有关的风险知之甚少。进行了一项病例对照研究，以调查育龄妇女的OPE，AP和邻苯二甲酸酯暴露是否与子宫肌瘤有关。为此，案例（n  = 32）和匹配的控件（n = 79）是根据韩国绝经前成年妇女的妇科超声检查结果选择的，并测量了几种OPE，AP和主要邻苯二甲酸盐的代谢产物。使用逻辑回归模型评估化学暴露与疾病状态之间的关联。作为第二分析，进行了多次化学暴露评估的因素分析。在OPE代谢产物中，> 80％的受试者中检出了磷酸二苯酯（DPHP），2-乙基己基磷酸苯酯（EHPHP）和1-羟基-2-丙基双（1-氯-2-丙基）磷酸酯（BCIPHIPP）。 。在AP中，在> 75％的尿液样本中检测到邻苯二甲酸二异壬酯（DINP）和邻苯二甲酸二（2-丙基庚基）酯（DPrHpP）的代谢产物。在Tris暴露量较高的女性中，子宫肌瘤的优势比（OR）明显较高（1，磷酸3-二氯-2-丙基）（TDCIPP）和磷酸三（2-丁氧基乙基）酯（TBOEP），对苯二甲酸二（2-乙基己基）酯（DEHTP），DPrHpP和二（异壬基）-环己烷-1， 2-二羧酸盐（DINCH）。此外，尿中邻苯二甲酸单（2-乙基-5-氧己基）酯（MEOHP），五种邻苯二甲酸二（2-乙基己基）代谢产物（∑5DEHP）和邻苯二甲酸单（4-甲基-7-羟基辛基）的总和（OH-MINP）明显更高。在因子分析中，DPrHpP和DEHP重载的因子与​​子宫肌瘤显着相关，支持单化学回归模型的观察。我们首次发现绝经前妇女中OPE和AP的几种代谢产物与子宫肌瘤风险增加有关。