A population-based case-control study of urinary bisphenol A concentrations and risk of endometriosis.
A population-based case-control study of urinary bisphenol A concentrations and risk of endometriosis.
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DOI：
10.1093/humrep/deu227
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发表时间：
2014-11
影响因子：
6.1
通讯作者：
K. Upson;S. Sathyanarayana;A. D. De Roos;H. Koch;D. Scholes;V. Holt
中科院分区：
文献类型：
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作者：
K. Upson;S. Sathyanarayana;A. D. De Roos;H. Koch;D. Scholes;V. Holt
研究问题双酚A(BPA)暴露是否与子宫内膜异位症的风险相关，子宫内膜异位症是育龄妇女的一种由雌激素驱动的疾病？摘要：我们的研究表明，尿BPA增加与非卵巢盆腔子宫内膜异位症的风险增加有关，但与卵巢子宫内膜异位症的风险无关。众所周知，双酚A是一种用于聚合物工业的大容量化学品，由于其在体内和体外显示出雌激素样作用以及广泛的人体暴露，一直是公众和科学关注的焦点。以前对双酚A和子宫内膜异位症的研究结果不一致，而且受到参与者抽样框架、样本量小或使用血清(浓度非常低/瞬时浓度)而不是尿液来测量双酚A浓度的限制。研究设计、规模、持续时间我们使用了女性子宫内膜异位症风险研究的数据，这是一项基于人群的子宫内膜异位症病例对照研究，在美国太平洋西北部一个大型医疗系统的女性参与者中进行。病例为1996至2001年间经手术证实的子宫内膜异位症患者，对照组为从引起病例的特定人群中随机选择的无子宫内膜异位症当前诊断或既往诊断的妇女。对象/材料、环境、方法对143例患者和287例人群对照的尿双酚A浓度进行了测定，方法采用病例诊断后采集的单一现场尿样。尿双酚A总浓度(游离态和结合态)用高效液相色谱-质谱法进行定量。我们使用非条件Logistic回归估计优势比(OR)和95%可信区间(CI)，并根据尿肌酐浓度、年龄和参考年份进行调整。我们还通过疾病亚型，卵巢子宫内膜异位症和非卵巢盆腔子宫内膜异位症，这可能是不同的病因来评估这种联系。主要结果和机会的作用我们没有观察到总体上尿BPA浓度与子宫内膜异位症之间有统计学意义的相关性。在评估尿双酚A总浓度与非卵巢盆腔子宫内膜异位症(第二与最低四分位数：OR 3.0；95%CI：1.2，7.3；第三与最低四分位数：或3.0；95%CI：1.1，7.6)时，我们观察到有统计学意义的正相关，但与卵巢子宫内膜异位症无关。局限性，谨慎的理由考虑到BPA的消除半衰期很短，我们的研究受到病例诊断后单个尿样采集时间的限制。因此，我们的双酚A测量可能不能准确地反映参与者在子宫内膜异位症发生的病因学相关时间段内的水平。此外，由于在这项以人群为基础的研究中，手术证实没有疾病是不可行的，所以一些对照可能患有未诊断的子宫内膜异位症。研究结果的更广泛意义通过使用基于人群的数据，更有可能是对照代表了双酚A暴露的潜在频率，而以前的研究用于对比对照接受手术评估的妇女，在这些研究中，手术适应症可能与双酚A暴露有关。本研究中观察到的显著相关性提示，双酚A可能影响月经周期内对激素反应的子宫内膜组织的正常动态结构变化，促进非卵巢盆腔子宫内膜异位症患者反流子宫内膜组织的建立和持续。有必要进行进一步的研究，以证实我们在子宫内膜异位症亚型中的新发现，这些亚型可能在病因上是不同的。研究资金/利益竞争这项工作得到了美国国立卫生研究院、国家环境健康科学研究所(资助号R03 ES019976)、尤尼斯·肯尼迪·施莱弗国家儿童健康和人类发展研究所(资助号R01 HD033792)、美国环保局科学成果(STAR)(资助号R82943-01-0)和国家护理研究所(资助号F31NR013092)的支持，以提供培训支持。这项工作部分得到了国家卫生研究院、国家环境卫生科学研究所的校内研究计划的支持。内容完全由作者负责，不一定代表国家儿童健康与人类发展研究所、国家环境健康科学研究所、国家护理研究所或国家卫生研究院的官方观点。作者没有实际或潜在的相互竞争的经济利益。试用注册号不适用。
STUDY QUESTION Is bisphenol A (BPA) exposure associated with the risk of endometriosis, an estrogen-driven disease of women of reproductive age? SUMMARY ANSWER Our study suggests that increased urinary BPA is associated with an increased risk of non-ovarian pelvic endometriosis, but not ovarian endometriosis. WHAT IS KNOWN ALREADY BPA, a high-volume chemical used in the polymer industry, has been the focus of public and scientific concern given its demonstrated estrogenic effects in vivo and in vitro and widespread human exposure. Prior studies of BPA and endometriosis have yielded inconsistent results and were limited by the participant sampling framework, small sample size or use of serum (which has very low/transient concentrations) instead of urine to measure BPA concentrations. STUDY DESIGN, SIZE, DURATION We used data from the Women's Risk of Endometriosis study, a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the US Pacific Northwest. Cases were women with incident, surgically confirmed endometriosis diagnosed between 1996 and 2001 and controls were women randomly selected from the defined population that gave rise to the cases, without a current or prior diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Total urinary BPA concentrations were measured in 143 cases and 287 population-based controls using single, spot urine samples collected after disease diagnosis in cases. Total urinary BPA concentration (free and conjugated species) was quantified using a high-performance liquid chromatography-mass spectrometry method. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for urinary creatinine concentrations, age and reference year. We also evaluated the association by disease subtypes, ovarian and non-ovarian pelvic endometriosis, that may be etiologically distinct. MAIN RESULTS AND THE ROLE OF CHANCE We did not observe a statistically significant association between total urinary BPA concentrations and endometriosis overall. We did observe statistically significant positive associations when evaluating total urinary BPA concentrations in relation to non-ovarian pelvic endometriosis (second versus lowest quartile: OR 3.0; 95% CI: 1.2, 7.3; third versus lowest quartile: OR 3.0; 95% CI: 1.1, 7.6), but not in relation to ovarian endometriosis. LIMITATIONS, REASONS FOR CAUTION Given the short elimination half-life of BPA, our study was limited by the timing of collection of the single urine sample, that occurred after case diagnosis. Thus, our BPA measurements may not accurately represent the participants' levels during the etiologically relevant time period for endometriosis development. In addition, since it was not feasible in this population-based study to surgically confirm the absence of disease, it is possible that some controls may have had undiagnosed endometriosis. WIDER IMPLICATIONS OF THE FINDINGS By using population-based data, it is more likely that the controls represented the underlying frequency of BPA exposure in contrast to prior studies that used for comparison control women undergoing surgical evaluation, where the indication for surgery may be associated with BPA exposure. The significant associations observed in this study suggest that BPA may affect the normal dynamic structural changes of hormonally responsive endometrial tissue during the menstrual cycle, promoting the establishment and persistence of refluxed endometrial tissue in cases with non-ovarian pelvic endometriosis. Further research is warranted to confirm our novel findings in endometriosis subtypes that may be etiologically distinct. STUDY FUNDING/COMPETING INTERESTS This work was supported by the National Institutes of Health, National Institute of Environmental Health Sciences (grant number R03 ES019976), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number R01 HD033792); US Environmental Protection Agency, Science to Achieve Results (STAR) (grant number R82943-01-0) and National Institute of Nursing Research (grant number F31NR013092) to KU for training support. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, National Institute of Nursing Research or the National Institutes of Health. The authors have no actual or potential competing financial interests. TRIAL REGISTRATION NUMBER Not applicable.