Around two-thirds of patients with Alzheimer’s disease (AD) are women, which could be related to the depletion of female sexual hormones at menopause. The replacement of these hormones with hormone therapy (HT) to possibly decrease AD risk or treat AD patients has generated conflicting results in the literature.
Our aim was to systematically review the relationship between HT use in postmenopausal women with AD and the risk of developing or treating AD symptoms.
The PubMed, LILACS, Scopus, Scielo, and Web of Science databases were searched from January 1994 to December 2020 using the descriptors ‘Alzheimer Disease OR Alzheimer’s Disease’ and ‘Hormone Replacement Therapy OR Estrogen Replacement Therapy’.
Observational and controlled clinical trials including postmenopausal women diagnosed with AD and evaluating HT efficacy were eligible for inclusion.
Extracted data comprise study design, covariates, inclusion criteria for sample selection, AD diagnosis criteria, biases, HT regimen, and cognitive measurement tools used.
Overall, 25 studies were selected. Among the 14 observational studies, 8 reported an improvement in cognitive function and a decrease in AD risk, especially in younger postmenopausal women. Five observational studies did not demonstrate any association between HT and AD, and one study reported an increase in AD risk, regardless of time of HT initiation. Of the 11 controlled clinical trials included, 7 showed an amelioration in cognitive function after HT. The remaining 4 trials saw no difference between HT and control.
Both observational and controlled clinical trials had methodological issues and discrepancies in inclusion criteria and HT protocols. These inconsistencies made it difficult to establish an association between HT and AD.

© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.