Hormone Replacement Therapy E4 Women

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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Re: Hormone Replacement Therapy E4 Women

Postby slacker » Sun Apr 07, 2019 7:43 am

Surupe wrote:I have been spending hours upon hours trying to find studies about Testosterone and it’s effects on Apoe4 carriers. I came across this study and am curious what people think.
https://scholar.google.com/scholar?q=ne ... FaXGT413UJ
I find my menopause brain fog is just awful and appears to be getting worse. I feel hopeless and have no idea what to do. I am taking BiEst and it’s doing nothing for me. My nurse practitioner is trying to talk me into adding testosterone . Anybody here have experience with it?


Hi Surupe;

Sorry to hear that you have worsening "brain fog." I tried to review your earlier posts, but may have missed some of your history. I think you mentioned "peri-menopause" earlier. Are you still having periods? If not, how long has it been?

You listed some lab results in an earlier post, but I didn't see estradiol listed. Has that not been checked? If so, what were the values?

I personally did not absorb the biest well, based on lab results. I switched to transdermal estradiol patch, which had subjective subtle improvements. Nothing dramatic. It may be worth trying the transdermal estradiol patch to see if it helps more than the biest. Stavia has an interesting story earlier in this thread on decreasing her dose of transdermal estradiol.

My testosterone (free and total) has been on the low side, but I opted out of adding on testosterone. I tend to want to minimize medical interventions if possible. My current hormone replacement is not covered by insurance. This decision was not made due to known long term issues. The information on testosterone in Bredesen's book is geared mostly towards men. The only mention I found for women is on page 209, indicating a target total testosterone between 30-70 ng/dL.

Concerning your link: it has 10 pages of references. I'm assuming that you are interested in feedback on the first article by Pfankach. The study was performed on male mice. I don't see how we can extrapolate findings to female humans.
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Re: Hormone Replacement Therapy E4 Women

Postby Surupe » Sun Apr 07, 2019 12:19 pm

Hi Slacker,
The article I meant to post said this:

Postmenopausal cognitive changes and androgen levels in the context of apolipoprotein E polymorphism

Iwona Bojar, Jarosław Pinkas, Mariusz Gujski, Alfred Owoc, Dorota Raczkiewicz, Kasia Gustaw-Rothenberg
Archives of medical science: AMS 13 (5), 1148, 2017
Results
In the group of postmenopausal women, higher testosterone concentration was associated with lower scores for Neurocognition Index (NCI)(p= 0.028), memory (p= 0.008) and psychomotor speed (p< 0.001). Presence of at least one APOE ε4 allele potentiated testosterone’s negative influence on cognitive functions (p< 0.05). Woman with a high normal level of DHEA scored significantly better in verbal (p= 0.027) and visual memory (p< 0.001) than other participants. APOE polymorphism did not modify the relationship between DHEA concentration and scores for cognitive functions.
Conclusions
Hormonal balance variations after menopause may influence brain processes concerned with cognition, especially memory and psychomotor speed. The observed effects may be related to androgens’ influence on higher cortical functions in the changed hormonal dynamics of the postmenopausal period.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575214/

According to my levels of FSH (84.2) my nurse practitioner says I am now post-menopausal.
My other levels are right where they should be which is why so I’m concerned about the brain fog...
Testosterone: 37
Estradiol: 59
Progesterone: 1.2
It’s making me wonder if my executive functioning, word finding and memory issues are due to Alzheimer’s. Depression is bad right now and I awake crying most mornings. I wasn’t depressed until I started having more cognitive issues.

I have decided to pay out some $$ and visit a Bredesen trained doctor in early summer to see if he can help. I reacted very poorly to the Keto diet which is one of the only parts of the protocol I’m not following. Also, I have not yet been tested for heavy metals which I would like him to do...
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Re: Hormone Replacement Therapy E4 Women

Postby babl » Sun Apr 07, 2019 3:00 pm

I've been on HRT for a couple of years now (I'm currently 54 y.o.) and have found so many benefits from it. But each of the four doctors I've seen in the past few years have very different opinions about how much for how long. I recently listened to Peter Attia's podcast on HRT and found it fascinating, but again there was no mention about dosage. The only thing mentioned was to throw some doubt on the current conservative approach (which most of the docs I've seen also advocate), which is "the least dosage for the shortest amount of time." All of my docs are of the opinion that I should be taking the lowest possible dosage to relieve menopausal symptoms, and that I should be tapering off of HRT completely within ten years.

Does anyone know of any studies or information on optimal dosages? Thanks!

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Re: Hormone Replacement Therapy E4 Women

Postby slacker » Sun Apr 07, 2019 4:49 pm

babl wrote: All of my docs are of the opinion that I should be taking the lowest possible dosage to relieve menopausal symptoms, and that I should be tapering off of HRT completely within ten years.

Does anyone know of any studies or information on optimal dosages? Thanks!


I doubt that there is a one size fits all. Conventional providers start at a low dose, and titrate up if the women continues to have quality of life menopausal symptoms. Cognitive issues are typically not addressed, and hormone replacement for cognition alone is not recommended from a conventional prospective. "Functional Medicine" providers tend to check individual hormone levels, and increase the dose if the levels aren't in a "ideal" range, including looking at the ratio of estradiol to progesterone. Appropriate length of treatment is unknown, and worthy of a discussion of benefits versus potential harm with one's provider.
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Re: Hormone Replacement Therapy E4 Women

Postby karelena » Fri Jul 05, 2019 11:46 pm

I finally finished reading all 68 pages of this discussion! It took weeks! Thank you to everyone who posted, now I need to review a few papers and make a decision about HRT. I am "peri-menopausal" now almost 3 months since my last cycle and starting to have hot flashes. Is this bad for my brain? I don't think hot flashes are due to lack of estrogen per se, it is believed that they are due to some complex interactions in the hypothalamus, probably having to do with excess FSH and other responses to the low serum estrogen that make the hypothalamus extra sensitive to tiny changes in body temperature. But the brain is not starved for estrogen, because it makes its own estrogen, right? Does anyone know what happens to brain estrogen in menopause?

It is very interesting that there was a comment (referenced in a post, comment was posted on the journal site) on the latest Finnish study that the populations of HRT + and HRT - are different because a lot of the APOE4 HRT - women died of CV disease so they did not live long enough to develop AD, thus the HRT + population had more APOE4 and the HRT - population has less APOE, and the hormone replacement was not causing the difference in AD incidence.

My inclination is to start HRT and follow the literature closely to see if there is a reason to stop or continue. It's too bad the literature is so conflicted and there are no large long term studies of APOE4 women. It may be different for us, more APOE4, induced by estrogen, may not be better, because of the interaction of APOE4 and beta amyloid. Serum estrogen may not even significantly contribute to brain estrogen. But then why do women have more AD than men? Do we have higher brain estrogen than men? Do we have higher CSF or brain APOE4?

I know I have not been active on this site for a while. It was all a little much to keep up with in addition to working full time and managing a household with 3 kids. But I do have a Bredeson trained physician and a one-time protocol that was done 2 years ago, that I try to follow. Lately I have some more free time as all the kids are teens and one is in college and they are a lot more independent. Also now I really feel like I am AGING, because of menopause. Now the stakes are higher and I want to optimize everything.

There's a really interesting article I posted to the Research topic, it's a review of 25 years of APOE research and it raises some interesting questions, including about whether more APOE4 expression is better or worse for us. And why are APOE4 female mice more symptomatic from AD than the males? They are pre-menopausal (on non-menopausal, I'm not sure if mice have menopause or not).

Thanks again for all of this discussion! I'm glad this site and all of you are here.

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Re: Hormone Replacement Therapy E4 Women

Postby karelena » Sat Jul 06, 2019 5:17 pm

MODERATOR EDIT: This paywalled paper has been removed because making it freely available is in violation of the Digital Millennium Copyright Act (DMCA). For anyone who can legally access SCiHub, it is available there. Here's the abstract:

Estrogen associated gene polymorphisms and their interactions in the progress of Alzheimer’s disease
https://www.ncbi.nlm.nih.gov/pubmed/24096044

Here is an article that was posted before on this topic and then deleted for some kind of copyright issue. I accessed it through work so I think I can attach it. It shows that there are SO MANY genes that are involved in the effect of estrogen in the brain. Very very complex. If you just want to take a quick look at the specific APOE4/estrogen gene interactions that part starts on page 62.

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Re: Hormone Replacement Therapy E4 Women

Postby Stavia » Sat Jul 06, 2019 5:27 pm

Karelena, lovely to hear from you.
Thanks for this discission. If you do start HRT, what form will you use?

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Re: Hormone Replacement Therapy E4 Women

Postby Plumster » Sun Jul 07, 2019 12:38 pm

Does anyone know of any studies or information on optimal dosages? Thanks!


Dosages are individualized and dependent on your needs. I take 0,075 mg estradiol (a very low amount), 200 mg progesterone, 5 mg DHEA every other day, and 5 mg pregnenolone. My doctor and I will tweak to try to reach the optimal levels listed below.

In The End of Alzheimer's, Dr. Bredesen recommends the following optimal levels (urine tests):

Estradiol level = 50-250 pg/ml
Progesterone level = 1-20 ng/ml
Estradiol : progesterone ratio = 10:100

DHEA sulfate = 350-430 mcg/dl [several on this forum have suggested that this number is unusually high.]
Cortisol (morning) – 10-18 mcg/dl
Pregnenolone = 50-100 ng/dL
Total testosterone (women) = 30-70 ng/dL
Last edited by Plumster on Sun Jul 07, 2019 1:09 pm, edited 2 times in total.
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Re: Hormone Replacement Therapy E4 Women

Postby slacker » Sun Jul 07, 2019 1:06 pm

Plumster wrote:
In The End of Alzheimer's, Dr. Bredesen recommends the following optimal levels (urine tests):



I don't see where recommended testing fluid is documented in the book's Table 2 starting on page 167. In the Hormonal Balance section on bioidentical hormones (page 208), the book states
...the optimal value for the reversal of cognitive decline as part of an overall program is unknown.

and
There is also disagreement about whether to measure estradiol in saliva, 24 hour urine samples, or through other methods.


My FM/Bredesen trained MD has generally tested my thyroid and sex hormones with blood. We are doing the DUTCH urine test for the first time to get additional information on estradiol metabolites to determine why my estrone level is high.
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Re: Hormone Replacement Therapy E4 Women

Postby Plumster » Sun Jul 07, 2019 1:14 pm

I don't see where recommended testing fluid is documented in the book's Table 2 starting on page 167. In the Hormonal Balance section on bioidentical hormones (page 208), the book states
...the optimal value for the reversal of cognitive decline as part of an overall program is unknown.

and
There is also disagreement about whether to measure estradiol in saliva, 24 hour urine samples, or through other methods.


Hmmm, not sure where I got the urine test part from. It was in my notes. I'll have to double check. The optimal levels are from pages 130-132 ("Goal") and 168.
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