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

Abstract

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, I 2 = 47.6%] and 1.05 (95% CI: 0.25-1.86, I 2 = 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, I 2 = 95.4%) and Fe (SMD = −0.59, 95% CI: −1.29-0.12, I 2 = 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.

Transferrin receptor-mediated reactive oxygen species promotes ferroptosis of KGN cells via regulating NADPH oxidase 1/PTEN induced kinase 1/acyl-CoA synthetase long chain family member 4 signaling

“…Wu et al revealed that TFRC induces cysteine deprivation and regulates system Xc − , which transports extracellular cystine to cytoplasm for the exchange of intracellular glutamate [ 10 ]. Iron metabolisms collectively participate in endocrine disorders, including diabetes [ 12 ], thalassemia [ 13 ], cervical cancer [ 14 ], and PCOS [ 15 , 16 ]. However, the underlying mechanisms are still unclear.…”

Zinc status, insulin resistance and glycoxidative stress in elderly subjects with type 2 diabetes mellitus

“…In a recent systematic review and meta-analysis, Yin et al showed that the serum Zn concentration was lower in polycystic ovary syndrome (PCOS) women with IR than in healthy women. However, there was no significant difference in serum Zn concentration when compared between healthy control and PCOS women without IR (34).…”

Involvement of ferroptosis in the granulosa cells proliferation of PCOS through the circRHBG/miR-515/SLC7A11 axis

“…The process of cell death is usually characterized by a large amount of iron accumulation and lipid peroxidation (32). Iron metabolism is involved in endocrine diseases, including PCOS (33,34), while its underlying mechanism remains unclear. SLC7A11, the cystine/glutamate antiporter, functions to transport cysteine for glutathione synthesis and antioxidation, which is an upstream regulator of the ferroptosis pathway and can inhibit ferroptosis when its expression is upregulated (35).…”