Abstract
The relationships between estrogen and cognitive functions have been explored in many experimental and observational studies with rather inconsistent outcomes. This study explored the relationship between hormone replacement therapy (estrogen-based) and Alzheimer's disease in postmenopausal women based on existing literature. A comprehensive search was conducted for relevant articles written in English language from 1990. PubMed, Medline search, Science direct and SCOPUS databases with keywords such as: 'Alzheimer's disease', 'hormone replacement therapy', 'pathogenesis of AD', 'epidemiology of AD in older women', 'biological role of oestrogen in neuroprotection', 'menopause and hormonal changes', and 'effects of HRT on cognitive functioning' were used for the search. The search strategy was based on Cochrane review recommendations and the relative risk was used to indicate the degree of relationship. A total of 898 citations were initially identified, of which 15 met the inclusion criteria for this study. Ten of the fifteen articles revealed that Estrogen Replacement Therapy (ERT) has a protective effect against Alzheimer's Disease (AD) in postmenopausal women with relative risks ranging from 0.28 - 0.95 (95% C.I. = 0.08 - 0.99), while the remaining five studies showed increased risk of AD in postmenopausal women exposed to ERT with relative risks ranging from 1.10 to 2.10 (95% C.I. = 0.60 - 3.50). Conclusively, longstanding commencement of HRT prior to the onset of menopause might be protective against the development of Alzheimer's disease on empirical basis, but does not seem to have any therapeutic value after the onset of the disease. Key words: Alzheimer's disease, hormone replacement therapy, oestrogen and neuroprotection.
Highlights
The epidemiologic trials that revealed the protective effects of hormone replacement therapy against Alzheimer's disease included those of Tang et al (1996), Paganini-Hill and Henderson (1996), Kawas et al (1997), Baldereschi et al (1998), Waring et al (1999), Slooter et al (1999), Zandi et al (2002), Henderson et al (2005), Shao et al (2012), Imtiaz et al (2017a) and Imtiaz et al (2017b)
Despite the several methodological issues raised with respect to the selection of the participants, the timing of the estrogen therapy, as well as the dosage and the formulation of the hormone(s) used in the studies cited, the common denominator amongst them is that the protective effects of estrogen against cognitive deterioration seems to be more pronounced when initiated in the early phase of menopause or at the early stages of the disease
The Cache County Study, for instance, that examined the relationship between HRT and Alzheimer’s disease (AD) in postmenopausal women revealed that women who used HRT had a reduced risk of AD compared with non-HRT users (Zandi, 2002)
Summary
Apart from the deterioration of memory, Alzheimer's disease is characterized by histopathological changes which include extracellular deposits of amyloid-β (A-β) peptides forming senile plaques, and the intracellular neurofibrillary tangles (NFT) of hyperphosphorylated tau in the brain which are commonly regarded as hallmarks of the disease (Dong et al, 2012). It accounts for about 50 to 60% of all dementia cases (Janicki and Schupf, 2010). With increasing life expectancy globally, the number of people of living with the disease will astronomically increase, since advanced age is one of the most consistent and important risk factors
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