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.