Statins and uterine fibroids: Potential for a novel therapeutic approach

Background Uterine fibroids are the most common benign gynecological tumors, affecting up to 70% of women. Only 25% of women with uterine fibroids are symptomatic. Despite the significant clinical burden, no satisfactory long‐term medical therapy is currently available. Definitive management often warrants surgery, which might result in significant morbidity and economic burden. Therefore, there is a growing need for novel and effective medical therapy. Statins have shown broad‐reaching pleiotropic effects on uterine fibroids, potentially inhibiting growth, reducing the incidence, and alleviating the symptoms. Objectives The current study aims to explore the pathophysiological mechanisms and clinical effects of statins on uterine fibroids. Search Strategy We retrieved relevant studies from PubMed, Cochrane Library, Embase, and ScienceDirect, published up to January 3, 2025. The study selection process was conducted using the semi‐automated tool Rayyan. Selection Criteria Full‐text articles of randomized controlled trials (RCTs), case–control studies, cross‐sectional studies, cohort studies, case series, and experimental studies in the English language that describe the pathophysiological mechanisms and clinical effects of statins on uterine fibroids were included. Review articles or book chapters were excluded. Data Collection and Analysis Key study characteristics were organized into predefined tables concerning outcome measures: pathophysiological mechanisms and clinical effects. Data synthesis involved a thematic analysis. A meta‐analysis was not performed due to study heterogeneity. Study quality assessment was conducted using the Newcastle‐Ottawa Scale (NOS), the Cochrane risk‐of‐bias (RoB1) tool, and the Quality Assessment Tool for In Vitro Studies (QUIN Tool). Main Results We included 13 studies screening 574 studies from four databases, where eight were laboratory‐based experimental studies, four were clinical studies, and one provided data on both. Quality assessment graded the studies as moderate to high quality. Statins exhibited diverse pharmacodynamic effects on leiomyoma cells, including a reduction in estrogen receptor‐α (ER‐α) levels and activity, alterations in intracellular signaling pathways that regulate cell proliferation, a decrease in extracellular matrix (ECM) production, induction of apoptosis, and improvements in altered cellular mechanotransduction, as well as changes in stemness markers. Clinical studies have demonstrated that statins have a significant impact on reducing fibroid volume and alleviating symptoms associated with fibroids. Conclusion Statins have demonstrated anti‐proliferative and pro‐apoptotic effects on uterine fibroids, resulting in symptomatic improvement and reduction in fibroid volume in clinical studies. However, given the paucity of evidence, it is challenging to conclude on the comparative efficacy, the most appropriate type of statin, the optimal dosing regimen, and the treatment duration, thereby creating a potential research gap. Therefore, we recommend well‐planned prospective studies to establish the role of statins in the management of uterine fibroids.