Is Hormone Replacement Therapy a Risk Factor or a Therapeutic Option for Alzheimer's Disease?

被引:23
|
作者
Mills, Zoe B. [1 ]
Faull, Richard L. M. [1 ]
Kwakowsky, Andrea [1 ,2 ]
机构
[1] Univ Auckland, Fac Med & Hlth Sci, Ctr Brain Res, Dept Anat & Med Imaging, Auckland 1023, New Zealand
[2] Ollscoil Na Gaillimhe Univ Galway, Galway Neurosci Ctr, Sch Med, Pharmacol & Therapeut, Galway H91 W5P7, Ireland
关键词
Alzheimer's disease; memory; dementia; cognition; estrogen; estradiol; hormone replacement therapy; FOREBRAIN CHOLINERGIC NEURONS; CUMULATIVE ESTROGEN EXPOSURE; ESTRADIOL IMPROVES COGNITION; CONJUGATED EQUINE ESTROGENS; ACTIVATED PROTEIN-KINASE; DENDRITIC SPINE DENSITY; HEALTHY CELL BIAS; POSTMENOPAUSAL WOMEN; DOUBLE-BLIND; TRANSDERMAL ESTRADIOL;
D O I
10.3390/ijms24043205
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for more than half of all dementia cases in the elderly. Interestingly, the clinical manifestations of AD disproportionately affect women, comprising two thirds of all AD cases. Although the underlying mechanisms for these sex differences are not fully elucidated, evidence suggests a link between menopause and a higher risk of developing AD, highlighting the critical role of decreased estrogen levels in AD pathogenesis. The focus of this review is to evaluate clinical and observational studies in women, which have investigated the impact of estrogens on cognition or attempted to answer the prevailing question regarding the use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords "memory", "dementia," "cognition," "Alzheimer's disease", "estrogen", "estradiol", "hormone therapy" and "hormone replacement therapy" and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that contribute to the conflicting findings of HRT in the prevention and treatment of age-related cognitive deficits and AD. The literature suggests that estrogens have a clear role in modulating dementia risk, with reliable evidence showing that HRT can have both a beneficial and a deleterious effect. Importantly, recommendation for the use of HRT should consider the age of initiation and baseline characteristics, such as genotype and cardiovascular health, as well as the dosage, formulation, and duration of treatment until the risk factors that modulate the effects of HRT can be more thoroughly investigated or progress in the development of alternative treatments can be made.
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页数:34
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