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Targeting Polycystic Ovary Syndrome (PCOS) Pathophysiology with Flavonoids: From Adipokine–Cytokine Crosstalk to Insulin Resistance and Reproductive Dysfunctions

Summary

Polycystic ovary syndrome (PCOS) is a common hormonal disorder affecting millions of women that causes irregular periods, infertility, and metabolic problems. Flavonoids are beneficial plant compounds found in fruits, vegetables, and tea that show promise in treating PCOS by improving insulin sensitivity, reducing inflammation, and balancing hormones. While current medications have limited benefits and side effects, flavonoid supplements could offer a safer, natural way to address multiple PCOS problems simultaneously. However, more large-scale clinical studies are needed to confirm their effectiveness and establish optimal dosing.

Background

PCOS is a prevalent endocrine-metabolic disorder affecting 8-13% of reproductive-age women globally, characterized by insulin resistance, hyperandrogenism, chronic inflammation, and reproductive dysfunction. Current pharmacological therapies like metformin and oral contraceptives provide only partial benefits with significant side effects. Flavonoids, plant-derived polyphenols, have emerged as promising multi-target therapeutic candidates due to their antioxidant, anti-inflammatory, insulin-sensitizing, and hormone-modulating properties.

Objective

This evidence-based review synthesizes mechanistic insights into how flavonoids modulate insulin signaling, adipokine-cytokine crosstalk, oxidative stress, and androgen excess in PCOS pathophysiology. The study aims to bridge gaps between preclinical and clinical data while highlighting translational evidence and emerging delivery systems to overcome bioavailability barriers.

Results

Preclinical evidence demonstrates that flavonoids improve insulin sensitivity through IRS-1/PI3K/AKT pathway activation, restore adipokine balance by upregulating adiponectin and downregulating leptin, suppress pro-inflammatory cytokines via NF-κB inhibition, enhance antioxidant defenses through Nrf2 pathway activation, and reduce hyperandrogenism through estrogen receptor modulation and steroidogenic enzyme suppression. Limited clinical trials report improvements in glucose metabolism, hormonal parameters, and menstrual regularity with flavonoid supplementation.

Conclusion

Flavonoids represent a promising class of nutraceuticals offering multi-target intervention against PCOS pathophysiology through simultaneous modulation of metabolic, inflammatory, and reproductive axes. However, clinical translation is constrained by poor bioavailability, heterogeneous study designs, and limited large-scale randomized controlled trials. Advanced delivery systems and well-designed clinical trials are essential to establish flavonoids as evidence-based adjuncts in PCOS management.
  • Published in:Pharmaceuticals (Basel),
  • Study Type:Review,
  • Source: PMID: 41155686, DOI: 10.3390/ph18101575
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