The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease

Abstract

The peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.

Effects of Pueraria candollei var mirifica (Airy Shaw and Suvat.) Niyomdham on Ovariectomy-Induced Cognitive Impairment and Oxidative Stress in the Mouse Brain

“…Moreover, increasing evidence suggests that gonadal hormones act as neurosteroids that are produced in the brain and, thus, rapidly alter cognition and other neural functions [4]. Therefore, the decrease induced in estrogen levels by menopause or ovariectomy may not only increase the incidence of inflammatory pathologies, but also decrease neurogenesis and neuronal plasticity [5].…”

The Perimenopausal Fatigue Self-Management Scale Is Suitable for Evaluating Perimenopausal Taiwanese Women’s Vulnerability to Fatigue Syndrome

“…The content validity showed that the CVI ranged from 0.82 to 1.00 for consistency, representativeness, relevance, and clarity of each construct, resulting in 25 items for the P-MFSMS. Perimenopause and menopause were based on the classification of the American Society for Reproductive Medicine’s Stages of Reproductive Aging Workshop (STRAW), which separates a woman’s life into seven segments, including segments −2, −1, and 0, ranging from the onset of menstrual cycles at menarche and the reproductive age to the peri-menopausal and postmenopausal phases [ 21 , 22 , 23 ]. In order to elucidate this distribution, women with regular menstrual bleeding during the last year were classified as premenopause; those with irregular bleeding during the last 12 months or with an age accompanied by less than one-year natural amenorrhea were defined as perimenopause; and the age at natural menopause was used to indicate the timing of menopause, which was confirmed after one year of amenorrhea [ 21 , 23 ].…”

“…Perimenopause and menopause were based on the classification of the American Society for Reproductive Medicine’s Stages of Reproductive Aging Workshop (STRAW), which separates a woman’s life into seven segments, including segments −2, −1, and 0, ranging from the onset of menstrual cycles at menarche and the reproductive age to the peri-menopausal and postmenopausal phases [ 21 , 22 , 23 ]. In order to elucidate this distribution, women with regular menstrual bleeding during the last year were classified as premenopause; those with irregular bleeding during the last 12 months or with an age accompanied by less than one-year natural amenorrhea were defined as perimenopause; and the age at natural menopause was used to indicate the timing of menopause, which was confirmed after one year of amenorrhea [ 21 , 23 ]. Regular exercise was defined as either three or more sessions per week, for at least 20 min per session, of jogging–running, hiking, biking, swimming, or dancing resulting in a medium-to-large increase in reported heart rate or five or more sessions per week, for at least 30 min per session, of any physical activity, such as walking, gardening or yard work, or calisthenics, that resulted in at least some increase in reported heart rate [ 24 ].…”

“… Data are presented as mean ± standard deviation or number (percentage). * Menstruation status: please refer to references [ 21 , 22 , 23 ]; ** regular exercise: please see the text and refer to [ 24 ]. …”

The Beneficial Role of Natural Endocrine Disruptors: Phytoestrogens in Alzheimer’s Disease

“…ER- α acts as a neuroprotective element against AD by maintaining intracellular signaling cascades [ 111 ]. ER- β is a potent regulator of the innate immune response as well as is involved in the regulation of neuronal mitochondrial function [ 112 ]. Besides, reduced expression of ER- α has been found in hippocampal neurons of AD subjects.…”