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Alzheimer’s disease is one of the biggest threats to human health, with over 100 million people expected to develop the condition by 2050. With such alarming statistics, researchers are looking for ways to reduce one’s chances of developing the disease. According to a new study, the answer may lie in hormone replacement therapy (HRT). HRT is a common tool used to address hormonal changes experienced by women. As such, this new research could be great news for women as they are more at risk for Alzheimer’s disease. 

Why Are Women More at Risk for Alzheimer’s Disease?

According to statistics, women are twice as likely to develop Alzheimer’s and there are a few theories as to why this is.

For one, Alzheimer’s is an aging-related disease, and women typically live longer than men. As such, this then makes the lifetime risk of the condition greater in women. 

Secondly, women experience hormonal changes in their lives, and researchers believe that these changes may increase their risk for Alzheimer’s disease. 

“The impact of estrogen decline on the brain during menopause is emerging as the main reason for the higher prevalence of Alzheimer’s disease in women,” explained Dr. Rasha Saleh to Healthline. 

Dr. Saleh adds that estrogen is responsible for the regulation of multiple physiological processes. As such, estrogen decline may cause an acceleration of Alzheimer’s disease-related pathologies.

Now, hormone replacement therapy is used to alleviate symptoms associated with the decline of estrogen changes. So, the theory put forward is that the use of HRT may serve to reduce the risk of Alzheimer’s disease. 

Hormone Replacement Therapy (HRT) vs APOE4 Gene

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APOE4 is known as the Alzheimer’s gene as having a single copy of APOE4 can triple one’s risk of developing Alzheimer’s, whereas having two copies can increase that risk by 8-12 times.

What’s more, women with the APOE4 gene have a greater risk of developing Alzheimer’s than men who also carry the same gene.

Now, as the reasoning behind a higher female prevalence is thought to be a combination of hormonal changes and the APOE4 gene, researchers have sought to determine if HRT could prevent cognitive decline in at-risk APOE4 carriers.

The study

In the study, published in Alzheimer’s Research and Therapy, the research team analyzed the data of 1178 Alzheimer’s-free women aged over 50. The participants were featured in the European Prevention of Alzheimer’s Dementia initiative. This initiative was set up to study their brain health over time. 

For the study, the researchers divided the women into two groups – those with APOE4 and those without. They then recorded anyone who was, or had been, treated with oral or transdermal estrogen, or estrogen plus progestogen, as having HRT.

The women partook in a range of cognitive tests. These tests assessed their attention, delayed memory, immediate memory, language, and visual construction skills. The women also underwent MRI scans to assess their brain volume, which decreases due to Alzheimer’s.

After compiling all the data, the team then analyzed the results to determine the impact of HRT on women carrying the APOE4 gene.

Can HRT prevent Alzheimer’s?

“We found that HRT use is associated with better memory and larger brain volumes among at-risk APOE4 gene carriers. The associations were particularly evident when HRT was introduced early – during the transition to menopause, known as perimenopause.” Dr. Rasha Saleh, study co-author.  

Dr. Saleh went on to highlight the significance of these findings as there have been very limited drug options for Alzheimer’s disease for twenty years and there is an urgent need for new treatments. 

“The effects of HRT in this observation study, if confirmed in an intervention trial, would equate to a brain age that is several years younger,” she says.

HRT as an Alzheimer’s drug?

The authors of the study noted that it wasn’t just the use of HRT that was significant. but also the when. The researchers noted that the earlier HRT was introduced, the larger the hippocampus volume.

Now, as exciting as these findings are, more studies are needed to better confirm HRT’s protectiveness against Alzheimer’s disease, as well as whether the benefits are solely for those looking to regulate their hormones. 

“It’s too early to say for sure that HRT reduces dementia risk in women, but our results highlight the potential importance of HRT and personalized medicine in reducing Alzheimer’s risk.” – Professor Michael Hornberger.

Want to know more?

While news of HRT as a tool for Alzheimer’s is promising, there is still currently no cure for Alzheimer’s. However, a newly approved drug may help delay the progression of the disease. In fact, lecanemab could be the Alzheimer’s breakthrough we’ve been looking for. 


GBD 2019 Dementia Forecasting Collaborators (2022). Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. The Lancet. Public health7(2), e105–e125.

Hsu, M., Dedhia, M., Crusio, W. E., & Delprato, A. (2019). Sex differences in gene expression patterns associated with the APOE4 allele. F1000Research8, 387.

Mielke M. M. (2018). Sex and Gender Differences in Alzheimer’s Disease Dementia. The Psychiatric times35(11), 14–17.

Saleh, R. N. M., Hornberger, M., Ritchie, C. W., & Minihane, A. M. (2023). Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimer’s research & therapy15(1), 10.

Pie Mulumba

Pie Mulumba

Pie Mulumba is a journalist graduate and writer, specializing in health, beauty, and wellness. She also has a passion for poetry, equality, and natural hair. Identifiable by either her large afro or colorful locks, Pie aspires to provide the latest information on how one can adopt a healthy lifestyle and leave a more equitable society behind.


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One Comment

  • Jonathan Raymond says:

    This study was not a clinical trial so cannot prove cause and effect. The WHI showed that estrogen, with or without progestin, increased the risk of Alzheimer’s and atrophied the hippocampus and frontal lobe. KEEPS also showed HRT in newly menopausal women caused greater brain atrophy, ventricular expansion, and white matter hyperintensities. So while these women were too young to show increased dementia risk, they did experience impaired verbal learning (Premarin) or impaired event recall and greater subjective memory complaints (estradiol). Moreover, a study last year of APOE carriers found they have greater levels of ER alpha in their hippocampi, which theoretically would make exogenous estrogen particularly risky.
    Bottom line – HRT does not prevent dementia. On the contrary, there is actually a new clinical trial out of Stony Brook testing the aromatase inhibitor letrozole (an antiestrogen used to treat and prevent breast cancer) to see if it will slow Alzheimer’s progression. I suspect THIS will actually work.