Comorbidity of the Mental and Cardiac Pathology in Patients of the Eastern Europe.

Estrogen, a key gonadal steroid hormone, is best known for its role in regulating the female reproductive system. However, its influence extends far beyond the reproductive tract, exerting widespread effects on the brain, liver, cardiovascular system, kidneys, skin, bones, and most notably, the gastrointestinal tract. Estrogen is crucial for maintaining homeostasis, modulating immune responses, preserving metabolic balance, and promoting antioxidant defense mechanisms via interacting with its receptors, particularly & . Estrogen regulates glucose and lipid metabolism, influences mitochondrial function, and protects against insulin resistance, further improving metabolic health. Within the gut, estrogen contributes to maintaining intestinal barrier integrity, modulating microbial diversity, and suppressing pro-inflammatory signalling pathways. These effects are crucial for sustaining a healthy gut associated metabolic dysregulation (GAMD). Estrogen deficiency, which occurs during menopause or following ovariectomy (OVX), disrupts the gut metabolic axis. The decline in circulating estrogen levels during the menopausal or postmenopausal state is associated with increased oxidative stress, heightened inflammatory cytokine production, dysregulated apoptosis, and substantial alterations in gut microbiome (GM) composition. These alterations may result in heightened intestinal permeability (leaky gut), systemic inflammation, and hepatic impairment, collectively known as hallmarks of gut-microbiome-metabolic axis disruption. Consequently, estrogen deficiency is strongly linked to the onset of metabolic impairment, including non-alcoholic fatty liver disease (NAFLD), insulin resistance, obesity, inflammatory bowel conditions, and gut dysbiosis. Although hormone replacement therapy (HRT) remains the conventional approach to mitigating the adverse effects of estrogen loss, long-term HRT use has been associated with several risks, including breast cancer, thromboembolic events, and cardiovascular complications. This has driven interest in safer, non-hormonal therapeutic alternatives that can target the underlying pathophysiological mechanisms without associated higher risks.