Role of estrogen in the regulation of central and peripheral energy homeostasis: from a menopausal perspective

Estrogen plays a prominent role in regulating and coordinating energy homeostasis throughout the growth, development, reproduction, and aging of women. Estrogen receptors (ERs) are widely expressed in the brain and nearly all tissues of the body. Within the brain, central estrogen via ER regulates appetite and energy expenditure and maintains cell glucose metabolism, including glucose transport, aerobic glycolysis, and mitochondrial function. In the whole body, estrogen has shown beneficial effects on weight control, fat distribution, glucose and insulin resistance, and adipokine secretion. As demonstrated by multiple in vitro and in vivo studies, menopause-related decline of circulating estrogen may induce the disturbance of metabolic signals and a significant decrease in bioenergetics, which could trigger an increased incidence of late-onset Alzheimer's disease, type 2 diabetes mellitus, hypertension, and cardiovascular diseases in postmenopausal women. In this article, we have systematically reviewed the role of estrogen and ERs in body composition and lipid/glucose profile variation occurring with menopause, which may provide a better insight into the efficacy of hormone therapy in maintaining energy metabolic homeostasis and hold a clue for development of novel therapeutic approaches for target tissue diseases.

Automated summary

Estrogen plays a vital role in regulating energy homeostasis throughout a woman's life, with receptors found in the brain and all body tissues. In the brain, estrogen via receptors regulates appetite, energy expenditure, and glucose metabolism. In the body, estrogen has beneficial effects on weight control, fat distribution, glucose and insulin resistance, and adipokine secretion. Menopause-related decline in estrogen levels can lead to metabolic disturbances and a higher risk for diseases like Alzheimer's, diabetes, hypertension, and cardiovascular disease in postmenopausal women. This article reviews the role of estrogen and receptors in body composition and metabolic changes during menopause, providing insight into hormone therapy and potential novel therapeutic approaches.