Premature menopause and risk of neurological disease: basic mechanisms and clinical implications.
Since basic scientific studies in the 1990s revealed dramatic gender differences in neurological damage from cerebral ischemia, significant evidence has accumulated for a neuroprotective role of ovarian-derived 17β-Estradiol (E2). Intriguingly, observational studies have further suggested that early and prolonged loss of ovarian E2 (premature menopause) leads to a doubled lifetime risk for dementia and a fivefold increased risk of mortality from neurological disorders, but some controversy remains. Here, we briefly summarize and analyze clinical cohort studies assessing the detrimental neurological outcomes of premature menopause. Furthermore, we discuss current basic science studies elucidating the molecular mechanisms underlying the enhanced risk of neurological disease in prematurely menopausal women and the "window of opportunity" for estrogen benefit. Finally, we highlight four critical issues in the field that require collaboration between basic scientists and clinicians for successful resolution, with the ultimate goal of maintaining optimal neurological health in prematurely menopausal women.
University System of Georgia MD/PhD Program, Georgia Regents University, Augusta, GA 30912, USA; Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, GA 30912, USA.
Erin L
EL
Scott
Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, GA 30912, USA.
Quan-Guang
QG
Zhang
Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Ratna K
RK
Vadlamudi
Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: dbrann@gru.edu.
Darrell W
DW
Brann
D015331:Cohort Studies; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008594:Menopause, Premature / Q000378:metabolism / Q000502:physiology*; D009422:Nervous System Diseases / Q000378:metabolism / Q000503:physiopathology*; D012306:Risk; D016387:Women's Health
D004967:Estrogens
Dementia; Estradiol; Estrogen; Menopause; Neurological disease