The Role of DNA Methylation in Insulin Resistance and Metabolic Dysregulation in Polycystic Ovary Syndrome Patients: A Systematic Review.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and metabolic disturbances, with insulin resistance (IR) playing a critical role in its pathogenesis. Emerging evidence suggests that epigenetic mechanisms, such as DNA methylation, may influence insulin signaling and metabolic pathways in PCOS by altering gene expression without changing the DNA sequence. This systematic review aims to evaluate the impact of DNA methylation on IR and metabolic dysfunction among PCOS patients by analyzing key genes involved in these processes. A comprehensive literature search was conducted using the databases Ovid, EMBASE, and Web of Science to analyze studies published between 2010 and 2025. Studies that evaluated DNA methylation and its association with IR and metabolic parameters in PCOS patients were included. Eligibility criteria followed the PRISMA guidelines. A total of 10 studies met the inclusion criteria. Hypermethylation of insulin receptor (INSR) and lamin A/C (LMNA) was associated with reduced insulin sensitivity, while hypomethylation of insulin receptor substrate 1 (IRS1) and bone morphogenetic protein 4 (BMP4) led to increased gene expression, contributing to metabolic dysregulation through increased androgen production. Epigenetic alterations were observed in granulosa cells and skeletal muscle tissues, highlighting tissue-specific differences. However, variability in study design and small sample sizes limited the generalizability of these findings. DNA methylation is pivotal in IR and metabolic dysfunction in PCOS. Understanding these epigenetic modifications may provide insights into potential therapeutic targets and lifestyle modifications aimed at reversing gene expression abnormalities and improving metabolic outcomes in patients suffering from PCOS and other metabolic disorders.