Hormone Therapy and Dementia – What You Should Know

Ladies, grab your reading glasses (or maybe a strong cup of coffee), because we’re diving into yet another study on hormone therapy (HT) and dementia. And let me tell you, this one is as clear as a foggy morning in menopause. To help make sense of it all, I sat down with Dr. Jennifer Davis from San Diego Menopause to break it down.

The Study in Question: Confusion Central

A recent study published in Science Advances (read it here) set off alarm bells, with click-bait headlines in the news suggesting that hormone therapy might contribute to tau accumulation in one area of the brain—which is associated with cognitive decline. Sounds scary, right? Well, not so fast.

According to Dr. Davis, the study has serious limitations that make it difficult to interpret:

• Tiny Sample Size: This was a small study with limited participants.
• Big Time Gaps: Women in the study had been on hormone therapy for an average of seven years, but their brain scans were done nearly 18 years after starting HT. That’s a massive time jump with a lot of variables in between.
• No Info on Hormone Type: We have zero details on whether these women were taking estrogen only, a combination of estrogen and progestin, oral vs. transdermal, or the dosage. (This is a big deal!)
• None of these women have dementia. Having these markers in your brain doesn’t mean you get dementia.
• Contradicts a Larger Study: A more recent 2024 study (read it here) with a bigger sample size found the exact opposite—showing that hormone therapy was associated with lower levels of tau.

Oral vs. Transdermal: The Missing Puzzle Piece

One of the biggest issues? Neither study separated out oral estrogen from transdermal estrogen.

Dr. Davis explained that in the U.S. and UK, most women are still prescribed oral estrogen despite growing evidence that transdermal may have different effects on the body, including potentially lower risks related to clotting and inflammation. Given the timing of this study, it’s likely that many of these women were on oral estrogen, which could impact the findings.

What About the ApoE4 Gene?

If you’re wondering whether you carry the ApoE4 gene, which has been linked to an increased risk of Alzheimer’s, you can get tested. A simple blood test or cheek swab can determine your APOE genotype, revealing whether you have the APOE2, APOE3, or APOE4 variant.

How to Get Tested:

• Consult a doctor – Your primary care physician or a genetic counselor can discuss the pros and cons of testing.
• Genetic testing – A lab test can analyze your DNA to determine your APOE status.
• At-home test kits – Some companies offer genetic testing kits that include APOE4 analysis, but it’s best to discuss the results with a medical professional.

Understanding the Results:

• One copy of APOE4 – May increase the risk of Alzheimer’s but is not a guarantee.
• Two copies of APOE4 – Significantly increases the risk, but still does not mean Alzheimer’s is inevitable.
• No APOE4 variant – Does not eliminate the risk of developing Alzheimer’s.

Important Considerations:

Genetic testing for APOE4 can have ethical and psychological implications. Learning your status can cause anxiety, and having the gene doesn’t mean you’ll develop Alzheimer’s. If you’re considering testing, it’s a good idea to talk to a doctor or genetic counselor first to make an informed decision.

Dr. Davis pointed out that in the larger 2024 study, a higher percentage of participants had the ApoE4 gene, yet hormone therapy still showed benefits in reducing tau accumulation. This raises an interesting question: Could estrogen play a protective role for women with ApoE4? More research is needed, but this adds another layer to the conversation about personalized menopause care.

Another twist? The larger 2024 study included more women who carry the ApoE4 gene—a gene linked to higher Alzheimer’s risk. Interestingly, these women actually showed lower tau accumulation with hormone therapy. Could estrogen be especially protective for women with ApoE4? More research is needed, but it raises fascinating questions.

Estrogen’s Multifaceted Role in Brain Health

It’s also important to remember that estrogen does much more for brain health than just its potential effects on tau and beta-amyloid. As outlined in Estrogen Matters, research has shown that estrogen:

• Increases the levels of an enzyme needed to synthesize acetylcholine, a key neurotransmitter involved in memory and learning.
• Stimulates the growth of nerve cells, regenerates axons, and decreases the nerve-cell death that happens in Alzheimer’s.
• Prevents dangerous calcium accumulation within nerve cells, protecting neurons from damage.
• Makes brain cells more responsive and sensitive to nerve growth factor, a protein responsible for the development of new neurons and the health of mature ones.
• Reduces the production of beta-amyloid, the substance that accumulates in amyloid plaques associated with Alzheimer’s.
• Prevents the buildup of the tau protein, which is implicated in neurodegenerative diseases.
• Enhances the action of glial cells, which regulate inflammatory responses after brain injury.
• Improves cerebral blood flow—women with extremely low estrogen levels due to illness or surgery show blood flow patterns similar to those with Alzheimer’s. In one study, administering estrogen reversed these changes in just six weeks.
• Promotes glucose uptake and metabolism in the brain. Since the brain consumes 20% of the body’s glucose despite making up only 2% of total body weight, estrogen plays a vital role in ensuring the brain has the energy it needs to function properly.

These findings reinforce that estrogen is far more than just a reproductive hormone—it’s a critical player in brain health and function. The conversation around HT must consider these broader neuroprotective effects, not just soundbites about individual studies.

The Takeaway: Stay Informed, Not Alarmed

Before you start ripping off your patches or tossing your hormone therapy in a panic, take a deep breath. We’ve been here before. Remember the 2002 WHI study and how its misinterpretation caused millions of women to suffer unnecessarily? Let’s not make the same mistake by reacting to alarming headlines without understanding the full picture.

Dr. Davis reassured me that there’s no reason to panic over this new study. Instead, it reinforces what we already know:

1. HT isn’t one-size-fits-all — the type, dose, and delivery method matter.
2. Longer use may have different effects than shorter use — the larger study showed benefits in women on HT for over 10 years. (I shall remain on my HT—thank you very much!)
3. More research is needed — particularly on the impact of oral vs. transdermal HT.
4. If you’re on HT, work closely with a menopause specialist to find the best approach for you.

Bottom line? 

Another click-bait headline. This is a “self-reported recall study” – we don’t know what hormones were used, and none of these women had dementia! We have lots of studies in younger women that HT decreases tau in your brain.  This is a negative study on normal brains with fearful headlines.  GRRRRRRRRRRRRRRRRRRRRRRRRRRRR!!!!!!

Stay fearless, fabulous, and informed!

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