The menopause-obesity axis in MASH progression: from estrogen decline to liver fibrosis

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) have emerged as major global health challenges, particularly among individuals with obesity and metabolic dysfunction. Menopause represents a critical hormonal transition characterized by estrogen deficiency, visceral adiposity, insulin resistance, and chronic low-grade inflammation, all of which may accelerate MASH progression and hepatic fibrosis in women. This narrative review summarizes current evidence regarding the menopause-obesity axis in MASH progression, focusing on molecular mechanisms, histopathological alterations, diagnostic biomarkers, imaging modalities, and emerging therapeutic strategies. Estrogen deficiency contributes to metabolic dysregulation through impaired insulin signaling, increased visceral adiposity, lipotoxicity, oxidative stress, and adipose tissue inflammation, thereby promoting hepatic steatosis and progression toward fibrosis. Histopathological progression is characterized by steatosis, hepatocyte ballooning, chronic inflammation, and extracellular matrix deposition. Non-invasive diagnostic approaches, including serum biomarkers, transient elastography, controlled attenuation parameter (CAP), and magnetic resonance imaging proton density fat fraction (MRI-PDFF), have improved disease detection and risk stratification. Lifestyle modification and sustained weight reduction remain the cornerstone of management, while emerging pharmacologic therapies such as glucagon-like peptide-1 receptor agonists, tirzepatide, and resmetirom demonstrate promising metabolic and hepatic benefits. Hormone-based and anti-fibrotic therapies may offer additional therapeutic potential in postmenopausal women with obesity-associated MASH. Collectively, the menopause-obesity axis appears to play a central role in hepatic injury and fibrosis progression through interconnected hormonal, metabolic, and inflammatory pathways. Improved understanding of sex-specific mechanisms may facilitate the development of personalized diagnostic and therapeutic approaches for postmenopausal women with MASLD and MASH.