Review of estrogen decline, diet, and microbial therapeutics for atherosclerosis in perimenopausal women

The risk of atherosclerosis rises markedly in perimenopausal women. The observed discrepancy between the traditional “estrogen cardioprotection hypothesis” and the complex effects of hormone replacement therapy in clinical practice suggests the existence of intermediary mechanisms that are not yet fully understood. Recent research indicates that the gut microbiota may play a pivotal role in this “estrogen paradox”. By integrating current evidence, this review systematically elucidates the core driving function of the “estrogen-gut-vascular axis” in disease progression: declining estrogen levels lead to intestinal barrier dysfunction and associated imbalances in microbial metabolites (e.g. reduced short-chain fatty acids and increased pro-inflammatory metabolites), collectively accelerating atherogenesis. Targeting this axis through dietary modification, microbial therapeutics, and precision hormone interventions may break this pathological cycle. Notably, effective nutritional strategies must consider food matrix, individual microbial metabolic capacity, and timing of intervention. Furthermore, building on extensive research into age-related shifts in gut microbiota, this review proposes the novel concept of ‘gut microbial age’ based on functional metabolic profiles, to quantify the functional state of host–microbiome interactions. This concept aims to provide new perspectives and tools for personalized cardiovascular risk assessment and precise intervention in perimenopausal women.