How insulin resistance drives polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) affects 6% to 20% of women of reproductive age worldwide, causing symptoms such as irregular menstruation, infertility, and excess androgens. Beyond reproductive problems, it raises long-term risks of type 2 diabetes and cardiovascular disease largely due to insulin resistance (IR), the most common metabolic feature of PCOS.

A comprehensive review published in Reproductive and Developmental Medicine by researchers from Zhejiang Chinese Medical University and Quzhou People’s Hospital summarizes current progress in understanding how IR contributes to PCOS and how it can be effectively managed.

The review synthesizes findings from genetic, cellular, and clinical studies. It describes how IR alters insulin signaling, particularly through the PI3K-AKT and MAPK-ERK pathways, disrupting glucose metabolism and promoting excessive androgen production. These imbalances impair ovarian function, disturb follicle development, and lead to ovulation disorders.

“Insulin resistance is not just a side effect of PCOS, it’s a central driver of the disease,” said the corresponding author, Dr. Fu. “Even women of normal weight may develop IR, which means that treatment should go beyond simple weight loss.”

The review also evaluates current and emerging therapies for improving insulin sensitivity. Lifestyle changes, including exercise and low-carbohydrate diets, remain the foundation of treatment. Very-low-calorie ketogenic diets (VLCKDs) have been shown to reduce visceral fat and improve ovulation more effectively than standard low-calorie diets. Glucagon-like peptide-1 receptor agonists (GLP-1RAs)—originally used for diabetes—lower insulin and lipid levels while offering cardiovascular protection. Inositol supplements help restore hormone balance and promote ovulation, although further studies are needed to confirm the addition as a routine treatment.

Traditional metformin therapy remains a mainstay, enhancing insulin sensitivity and improving reproductive outcomes. Meanwhile, newer directions such as probiotic supplementation, capable of correcting gut microbiota imbalances linked with IR, show potential as low-risk, adjunctive options.

“Gut health is one of the most promising frontiers,” said co-author Dr. Yi. “Women with PCOS often have fewer beneficial bacteria like Lactobacillus, and probiotics may help improve both metabolic and hormonal balance.”

The review also calls for greater focus on lifelong management. Many women discontinue treatment once fertility goals are achieved, missing opportunities to prevent long-term complications such as diabetes, cardiovascular disease, and endometrial cancer.

By compiling recent research on insulin resistance and PCOS, this review provides a valuable foundation for developing more personalized, mechanism-based interventions, targeting not just symptoms, but the underlying metabolic dysfunction at the heart of PCOS.