Early inflammatory changes in perimenopause: A risk for neurodegeneration

Perimenopause is a natural transition into menopause which is often characterized through fluctuating estrogen levels, and associated with age-related increase in the risks of neurodegenerative diseases. A decline in estrogen hormone levels disrupts immune regulation and leads to impaired neuroinflammation and mitochondrial function, which eventually results in poor cognitive function. Estrogen receptor ER-β seems to play a neuroprotective role in modulating inflammation and oxidative stress. However, reduced activation during perimenopause promotes neurodegeneration. Hormone Replacement Therapy (HRT) is primarily employed to ameliorate menopausal symptoms and enhance cognitive function. However, it bears potential risks, including augmenting the risk of cardiovascular disease and cancers. Dietary interventions and antioxidants exhibits neuroprotective potential and supporting the pharmacological strategy of inflammation management. Regular physical activities and stress management contribute to countering systemic inflammation with effective brain health. Hence, an integrated approach incorporating hormonal balance, lifestyle changes, and targeted therapy toward neuroinflammation is critical to enhancing women's long-term health outcome. Understanding the mechanisms of neurodegenerative processes induced by perimenopause can create a valuable basis for producing effective interventions to manage cognitive function and overall health in peri-and post-menopausal women. This review emphases the significance of addressing systemic inflammation in perimenopause to improve health and quality of life for women. Keywords: Perimenopause; Systemic inflammation; Estrogen regulation and Neurodegeneration