Multidimensional regulation of estrogen signaling in pelvic floor connective tissue homeostasis and remodeling

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Pelvic organ prolapse (POP) is a prevalent condition that significantly impairs women's quality of life and is closely linked to dysregulated estrogen signaling. This review examines the mechanisms through which estrogen, acting via nuclear receptors (ERα and ERβ) and the membrane receptor G protein-coupled estrogen receptor (GPER), regulates pelvic floor connective tissue homeostasis through both genomic and non-genomic pathways. Key regulatory effects include the promotion of collagen and elastin synthesis, inhibition of matrix metalloproteinase (MMP) activity, modulation of fibroblast function-including mitigation of cellular senescence and enhancement of migratory and anti-apoptotic capacities-as well as integration with mechanical signaling through the integrin-YAP/TAZ axis. Additionally, estrogen helps suppress chronic inflammation and influences macrophage polarization. Clinical evidence indicates that estrogen deficiency and an elevated ERα/ERβ ratio contribute to extracellular matrix degradation, a hallmark of POP. Although local estrogen therapy can improve perioperative tissue quality, its long-term efficacy in structural restoration remains limited. Emerging therapeutic approaches include selective estrogen receptor modulators, ERβ-specific agonists, and personalized interventions based on receptor profiling and genetic markers. Future research should leverage patie

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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