Fisetin is a naturally occurring flavonoid, a type of polyphenol found in fruits and vegetables such as strawberries, apples, persimmons, and onions. It has gained increasing attention for its antioxidant properties (enhancement of SOD1 and CAT activity and reduction of ROS), anti-inflammatory effects (suppression of NF-κB signaling), and senotherapeutic activity (senolytic and senomorphic effects). Although numerous studies have examined fisetin in the context of aging and chronic diseases, its role in women’s reproductive health has not been systematically explored. Mechanistically, fisetin regulates several pathophysiological processes, including ovarian aging, fibrosis, angiogenesis, and hormonal regulation, suggesting its potential relevance to female reproductive health and disease. Indeed, emerging evidence indicates that fisetin may support ovarian function and hormonal balance, modulate fibrosis and metabolism in benign gynecologic conditions, and suppress cell growth in gynecologic cancers. Early-phase clinical studies in non-gynecologic conditions suggest an acceptable safety profile, although evidence in reproductive health remains absent. This review summarizes current experimental and clinical evidence, identifies critical gaps in mechanistic understanding, and discusses future directions for advancing fisetin as a promising non-hormonal therapeutic option in reproductive health and diseases.

Uterine leiomyomas or fibroids are a common but pernicious benign tumor impacting between 70–80% of women of reproductive age. Despite their high prevalence, the etiology of uterine fibroids is not fully understood. This review aims to highlight the distinct metabolic features that uterine fibroids adopt to meet biosynthetic demands, support proliferation, extracellular matrix production, survival, and fibrosis. Specifically, we posit the role of glycolytic reprogramming—an adaptation in fibrosis across organs (lung, kidney, heart, and liver) as a major contributor to uterine fibroid development. Previous genetic, transcriptomic, proteomic, and metabolic studies have drawn strong links between metabolism and uterine fibroid biology and identified genotype-specific metabolic alterations such as fumarate hydratase (FH) deficiency and mediator of RNA polymerase II transcription (MED12) gene mutations. Studies in non-uterine models have linked glycolysis to ECM production and fibrosis through activation of transforming growth factor-beta (TGF-β) and the canonical Wnt pathway (Wnt/β-catenin) signaling, supporting them as potential key pathways in uterine fibroid pathogenesis via glycolytic reprogramming. Other metabolic regulators, such as hypoxia-inducible factor 1-alpha (HIF-1α), mammalian target of rapamycin (mTOR), and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), may also sustain the fibrotic phenotype through coupling signaling that drives ECM production to metabolic programming. Overall, the proposed metabolic perspective of uterine fibroid pathogenesis invites further exploration of mechanistic investigation in uterine-specific models and therapeutic targeting through larger cohort studies.

Objective: This study evaluated the association between polyps, a common structural cause of abnormal uterine bleeding (AUB) and bacterial vaginosis (BV), the most common vaginal infection affecting women worldwide. Materials and Methods: A single-institution retrospective study was performed of 283 patients diagnosed with polyps between 2016 and 2021. Data collected included demographics, polyp-related bleeding symptoms, and the number and timing of BV diagnoses. Characteristics of patients who developed BV within 1 year before and/or within 3 years after polyp diagnosis were compared with those of patients with chronic BV and no BV diagnoses using χ ² and Kruskal-Wallis tests. Odds ratios were estimated using logistic regression models. Results: A majority (72%) of patients experienced AUB associated with polyps, with a higher prevalence of AUB in the Chronic and New BV cohorts relative to the No BV cohort (76% and 76% vs 63%). Specifically, patients with menorrhagia or heavy menstrual bleeding (HMB) were more likely to develop BV after polyp diagnosis compared with patients without menorrhagia or HMB (78% vs 56%, P =.001). Conclusions: This study demonstrated an association between menorrhagia or HMB caused by polyps and BV diagnoses. Future prospective studies are needed to further characterize the relationship between the structural causes of AUB and BV.