How does menopausal hormone replacement therapy (HRT) affect the risk of dementia?

Updated: Sep 13, 2021
  • Author: Nicole K Banks, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Increasing age is the most important risk factor for dementia, and most of the risk is attributed to Alzheimer disease, cerebrovascular disease, or a combination of both. The decrease in the supply of neuronal growth factors with age appears to mediate neural pathology. Estrogen is believed to be one such growth factor. It enhances cholinergic neurotransmission and prevents oxidative cell damage, neuronal atrophy, and glucocorticoid-induced neuronal damage.

In theory, HT in postmenopausal women should prevent and help treat dementia and related disorders. However, various studies have failed to provide a consensus on this aspect. This lack is largely because of issues of selection bias, as well as extreme heterogeneity in study participants, treatments, and cognitive function tests applied, and doses of HT.

Early studies showed that estrogens may delay or reduce the risk of Alzheimer disease, but it may not improve established disease. [21]

Contrasting new findings from a memory substudy of the WHI showed that older women taking combination hormone therapy had twice the rate of dementia, including Alzheimer disease, compared with women who did not. The research, part of the Women’s Health Initiative Memory Study (WHIMS) revealed a heightened risk of dementia in women aged 65 years or older who took combination HT. This risk increased in women who already had relatively low cognitive function at the start of treatment. [22]

Authors of the Cache County Study were the first to propose the window-of-opportunity theory. [23] The risk of Alzheimer disease varied with duration of drug use. Previous use of HT was associated with a decreased risk. However, no benefit was apparent unless current HT was used for longer than 10 years.

At present, no definite evidence supports the use of HT to prevent or improve cognitive deterioration.

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