Hormone Replacement Therapy E4 Women

[SusanJ]

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

The study shows that HRT use is associated with better memory, cognition and larger brain volumes in later life among women carrying the APOE4 gene—the strongest risk factor gene for Alzheimer’s disease.

The research team found that HRT was most effective when introduced early in the menopause journey during perimenopause.

Summary in Neuroscience

HRT introduction is associated with improved delayed memory and larger entorhinal and amygdala volumes in APOE4 carriers only. This may represent an effective targeted strategy to mitigate the higher life-time risk of AD in this large at-risk population subgroup. Confirmation of findings in a fit for purpose RCT with prospective recruitment based on APOE genotype is needed to establish causality.

Full article

[JML]

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

Thanks for posting this. I wish I had known this 20 years ago!

[NF52]

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

Thanks for posting this. I wish I had known this 20 years ago!

20 years ago no doctor would touch HRT because of the flawed studies on heart attack risk. Sadly, many of those women are now in the mid-late 70's and bearing the results in frailty and cognition.

[Maria4/4]

Hello ladies,

I started HRT 3 months ago. I made some blood work and my estradiol is 50,6pg/ml (I use a pash of 50mg/day) and my progesterone level is 4,22ng/ml (I take daily 100mg).

I saw here in the forum that Dr. Dale Bredesen recommends a ratio of 10:100 between progesterone and estradiol, so my progesterone level should be 5ng/ml.

Has anyone had this issue? Is it recommended to take more progesterone?

Thanks for your help,
Maria 4/4

[JML]

Has anyone had this issue? Is it recommended to take more progesterone?

Hi Maria--that is a really good question for your doctor. You are not too far from the target, but your practitioner would be the best person to help you get to the right levels. Hopefully they will know how to tweak progesterone to get you there. You might ask her/him if adding some topical progesterone would be a good idea.

Maybe someone else in the group has had some experience with this and will chime in. Good luck!

[Gail]

Hello ApoE 4 Ladies,

Have you seen the article in the New York Times. I would love to see a critique of this from the very brilliant women on this forum.
https://www.nytimes.com/2023/02/01/maga ... erapy.html

It is a bit of a summary of things we already know. But in addition it says this among a lot of other things that are of interest to us.

"In the past 15 years, four randomized, controlled trials found that taking estrogen had no effect on cognitive performance. But those four studies, Maki points out, did not look specifically at women with moderate to severe hot flashes. She believes that might be the key factor: Treat the hot flashes with estrogen, Maki theorizes, and researchers might see an improvement in cognitive health. In one small trial Maki conducted of about 36 women, all of whom had moderate to severe hot flashes, half of the group received a kind of anesthesia procedure that reduced their hot flashes, and the other half received a placebo treatment. She measured the cognitive function of both groups before the treatment and then three months after and found that as hot flashes improved, memory improved. The trial was small but “hypothesis generating,” she says.

Even adjusting for greater longevity in women, Alzheimer’s disease is more frequent in women than men, one of many brain-health discrepancies that have led researchers to wonder about the role that estrogen — and possibly hormone therapy — might play in the pathways of cognitive decline. But the research on hormone therapy and Alzheimer’s disease has proved inconclusive so far."

Do you Apoe4 people have any thought on this article? Thank you for sharing.
Gail 3/4

[Maria4/4]

Hello ApoE 4 Ladies,

Have you seen the article in the New York Times. I would love to see a critique of this from the very brilliant women on this forum.
https://www.nytimes.com/2023/02/01/maga ... erapy.html

It is a bit of a summary of things we already know. But in addition it says this among a lot of other things that are of interest to us.

"In the past 15 years, four randomized, controlled trials found that taking estrogen had no effect on cognitive performance. But those four studies, Maki points out, did not look specifically at women with moderate to severe hot flashes. She believes that might be the key factor: Treat the hot flashes with estrogen, Maki theorizes, and researchers might see an improvement in cognitive health. In one small trial Maki conducted of about 36 women, all of whom had moderate to severe hot flashes, half of the group received a kind of anesthesia procedure that reduced their hot flashes, and the other half received a placebo treatment. She measured the cognitive function of both groups before the treatment and then three months after and found that as hot flashes improved, memory improved. The trial was small but “hypothesis generating,” she says.

Even adjusting for greater longevity in women, Alzheimer’s disease is more frequent in women than men, one of many brain-health discrepancies that have led researchers to wonder about the role that estrogen — and possibly hormone therapy — might play in the pathways of cognitive decline. But the research on hormone therapy and Alzheimer’s disease has proved inconclusive so far."

Do you Apoe4 people have any thought on this article? Thank you for sharing.
Gail 3/4

Very interesting Gail. Thanks for sharing.

I don’t know about the studies, but I know my own experience. Since I began with HRT my symptoms improved. I don’t know if it is because of estrogen or because I started to sleep better.

I also know that my mother ‘s symptoms began after she stopped HRT. She stopped at 60 and I knew that something was wrong when she was 65. She died last year with Alzheimer.

I believe HRT is important, but I would love to see a proof of it.

Maria 4/4

[Veero]

My mom is 76 and she has to have at least one e4. HRT evangelist and poo-pooed the risk in those papers that originally spooked the doctors. Doing well cognitively and active and engaged, more than most people at her age. Severe incontinence and other symptoms when she skips more than a day of the HRT. She searches out and sends me the HRT benefit papers on pub med between her other projects. She will stay on them until she dies I think. Her diet has been crappy for decades so something else is keeping her from getting Alzheimer’s.

[kellipsf]

8 months ago I first became aware of the suspected relationship between perimenopause and alzheimer's, and alcohol. I knew I had one copy of ApoE4 but did not know that a drop in estrogen initiates even more havoc for those predisposed for AD. Nor did I know til I stumbled upon a single sentence in a book on menopause that said "Stop drinking if you carry the Apoe4 gene". I queried my endocrinologist and she also said "stop drinking" if you have the gene. Why is no one talking about this? I am 56 and started on HRT's 3 years ago, but so wish I'd been informed and stopped drinking well before last year.

[NF52]

8 months ago I first became aware of the suspected relationship between perimenopause and alzheimer's, and alcohol. I knew I had one copy of ApoE4 but did not know that a drop in estrogen initiates even more havoc for those predisposed for AD. Nor did I know til I stumbled upon a single sentence in a book on menopause that said "Stop drinking if you carry the Apoe4 gene". I queried my endocrinologist and she also said "stop drinking" if you have the gene. Why is no one talking about this? I am 56 and started on HRT's 3 years ago, but so wish I'd been informed and stopped drinking well before last year.

Hi kellipsf,

It's begun to be written about for ApoE4 carriers, but only since researchers got large grants to go back and reanalyze many thousands of people followed for decades. Doing so often means taking old blood samples and re-testing them for ApoE status, since it wasn't tested either by doctors or in populations studies until very recently.
Research into prevention of both Alzheimer's and vascular dementia often looks at years of education, exposure to pollution, cognitive baseline scores, and health conditions like high blood pressure, coronary artery disease, Type2 diabetes, obesity, smoking, alcohol use and prior head injuries. All of those are important too, and you may be doing terrifically on those even if you enjoyed alcohol.

Many doctors would be likely to advise the average person that a glass of red wine with dinner may be good for your heart--because for the 75% of the population without ApoE4, that seems to be true!

Here's an excerpt from an article published in 2021 that I like for its readability. One of the coauthors of Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers was, until very recently, the director of the Alzheimer's research center and memory clinic at Weill-Cornell Medical Center in NYC and is a strong believer in the effect of lifestyle on risk.

6.3.4. Limit Alcohol

While light alcohol consumption has been associated with a decreased risk of AD in general [127], this relationship does not appear to hold in ApoE4 carriers. Consumption of any amount of alcohol may increase the risk of AD for ApoE4 carriers [128,129,130]. In one study, both light and moderate alcohol consumption were associated with improvement in learning and memory for non-carriers, but with a decline in learning and memory for carriers [129]. Other studies found that ApoE4 carriers who consumed alcohol one or more times per month had a higher risk of AD than those who never consumed alcohol [128] and the risk of AD for carriers increased with increasing amounts of alcohol consumption [130] These data suggest that alcohol consumption should be limited, especially in ApoE4 carriers.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073598/

I have two copies of ApoE4, and am 70 years old and never had the benefit of HRT, which was mistakenly thought to cause heart attacks in menopausal women 20 years ago. (That was only true in a very small percentage of women over age 70; who today are not prescribed HRT.) I rarely have alcohol, but if it's a special occasion, I don't feel I'm risking my brain to have a glass of red or white wine once every 6 months.

You're at a great age to plan for a long, healthy life!