Data_Sheet_1_Serum Trace Elements in Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.docx

Polycystic ovary syndrome (PCOS) is reported to be associated with certain trace elements. However, previous data are inconsistent and potentially biased due to small sample sizes. The potential utility of trace element levels for screening of PCOS remains to be established. The aim of this meta-analysis was to investigate the potential relationships between PCOS and serum levels of zinc (Zn), copper (Cu), magnesium (Mg), iron (Fe) and ferritin. We carried out a literature search of PubMed, EMBASE, and Web of Science for relevant cross-sectional/case-control studies published prior to October 2019. Random-effect models were used to estimate the overall standard mean differences (SMDs) between PCOS and healthy control subjects. The screening value of potential microelement biomarkers for PCOS was assessed using the receiver operating characteristic (ROC) curve. Twenty-one studies featuring 2,173 women with PCOS and 1,897 healthy women were selected for analysis. Our results showed that Cu and ferritin levels were significantly higher in women with PCOS than healthy controls, with SMDs of 0.52 [95% confidence interval (CI): 0.38–0.67, I2 = 47.6%] and 1.05 (95% CI: 0.25–1.86, I2 = 97.0%), respectively. The serum ferritin concentration was distinguished as a potential biomarker for PCOS based on the high area under ROC curve value of 0.71 (95% CI: 0.57–0.86). Although we did not identify a statistical association between serum Zn concentration and PCOS overall, the concentration of Zn in PCOS women with insulin resistance (IR) was lower than that in healthy women (SMD = −0.89, 95% CI: −1.73 to −0.06). Furthermore, the concentrations of Mg (SMD = 0.31, 95% CI: −0.32–0.94, I2 = 95.4%) and Fe (SMD = −0.59, 95% CI: −1.29–0.12, I2 = 97.2%) were not statistically significant between the PCOS and control groups. We generated hypothetical pathways for associations among serum Cu, ferritin and PCOS. The serum concentrations of both Cu and ferritin were significantly higher in women with PCOS, and ferritin was identified as a potential early indicator for PCOS screening. Further studies are essential to determine the specific underlying mechanisms.

据报道，多囊卵巢综合征（Polycystic ovary syndrome, PCOS）与某些微量元素存在关联。然而，既往研究数据因样本量较小，结果存在不一致性且可能存在偏倚。目前，微量元素水平用于多囊卵巢综合征筛查的潜在价值仍有待明确。本荟萃分析旨在探讨多囊卵巢综合征与血清锌（zinc, Zn）、铜（copper, Cu）、镁（magnesium, Mg）、铁（iron, Fe）及铁蛋白的水平之间的潜在关联。我们对PubMed、EMBASE及Web of Science数据库进行了文献检索，纳入2019年10月之前发表的相关横断面/病例对照研究。采用随机效应模型估算多囊卵巢综合征患者与健康对照受试者的总体标准均数差（standard mean difference, SMD）。通过受试者工作特征（receiver operating characteristic, ROC）曲线评估潜在微量元素生物标志物用于多囊卵巢综合征筛查的价值。最终纳入21项研究，共包含2173例多囊卵巢综合征患者与1897例健康女性。结果显示，多囊卵巢综合征患者的血清铜与铁蛋白水平显著高于健康对照组，标准均数差分别为0.52[95%置信区间（confidence interval, CI）：0.38~0.67，I²=47.6%]与1.05（95%CI：0.25~1.86，I²=97.0%）。基于受试者工作特征曲线下面积为0.71（95%CI：0.57~0.86）的较高数值，血清铁蛋白浓度被确定为多囊卵巢综合征的潜在生物标志物。尽管整体而言未发现血清锌浓度与多囊卵巢综合征存在统计学关联，但合并胰岛素抵抗（insulin resistance, IR）的多囊卵巢综合征患者的血清锌浓度低于健康女性（SMD=-0.89，95%CI：-1.73~-0.06）。此外，多囊卵巢综合征患者与对照组的血清镁（SMD=0.31，95%CI：-0.32~0.94，I²=95.4%）与铁（SMD=-0.59，95%CI：-1.29~0.12，I²=97.2%）浓度未呈现统计学差异。我们针对血清铜、铁蛋白与多囊卵巢综合征之间的关联提出了假说通路。多囊卵巢综合征患者的血清铜与铁蛋白浓度均显著升高，且铁蛋白被确定为多囊卵巢综合征筛查的潜在早期指标。未来仍需开展进一步研究以明确其具体潜在机制。