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

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.