Hormone Replacement Therapy E4 Women

[Orangeblossom]

Hi, this article has been mentioned in the press today, a large study in Finland (with high rates of APOE4)- wondered what your thoughts were on it. I will post a link.

https://www.bmj.com/content/364/bmj.l665

[slacker]

Hi Orange, good to see you on the boards!

Drs Bluming and Tavris do a thorough job of showing how the Women's Health Initiative (WHI) based conclusions about hormone replacement on data that was not statistically significant. They also showed how the use of "data mining" artificially skews results. When the overall data does not support the hypothesis, the data is broken down into multiple subgroups looking for some result that is more "acceptable." I highly recommend listening to the podcast listed above and/or reading their book "Estrogen Matters." It's helpful to get a different perspective.

With that being said, I took a quick look at the Finnish study linked from the BMJ. I am not an expert at statistics, but I tried to look at the data presented from the perspective of what I learned from Drs Bluming and Tavris. Luckily, we have the entire BMJ article and not just an abstract. Table 3 is an example. Generally, "statistically significant" results have a P value of less than 0.05. You will see in this table that there are many results that have a P value greater than this, and therefore not statistically significant. Statistically significance without medical significance is another issue. In this table, you can see that data was broken down into 2 age groups, estrogen alone versus estrogen and progestogen, and length of treatment. Women who started combined hormone replacement before age 60 had a statistically increased risk of AD after 10 or more years of hormone replacement. Women who started HRT after the age of 60 had a statistically increased risk of AD up to 10 years of combination replacement, but did not have this risk with greater than 10 years of use. This doesn't make much sense to me - what is the mechanism of action? Is it a sample size problem? Data mining? Any other thoughts?

[Orangeblossom]

Hi Slacker, thanks- hope you are doing OK.

I'm not quite sure what to think. I guess I was a bit disappointed it didn't seem to show more of a protective effect, and wanted to share it to get sone perspective on it. I wondered about they type of HRT they were using and if it was the same as the equine kind of not, that was of interest, as that seemed to be an issue in the previous Women's health study.

Here is how it is being reported in the British press, https://www.bbc.co.uk/news/health-47471142

"GPs are urging women not to be alarmed by research linking long-term hormone replacement therapy (HRT) use with a small increased risk of Alzheimer's.
They say HRT is an effective and safe treatment for most women with menopause symptoms and the risk is "extremely low".
The BMJ research looked at data on 170,000 women in Finland over 14 years.
It found a 9%-17% increased risk for Alzheimer's, particularly in women taking HRT for more than 10 years.
This equates to between nine and 18 extra cases of the disease per year in every 10,000 women aged between 70 and 80, the researchers said.
But the study was observational and, as a result, it cannot be said for certain that other factors had not affected the results.
Other studies have found that HRT actually improves brain function.

The Royal College of GPs said the research does not prove that HRT causes Alzheimer's disease, and women currently taking it should continue to do so.
Prof Helen Stokes-Lampard, chairwoman of the College, said: "Hormone replacement therapy can be of greatest benefit to many women who are suffering from some of the unpleasant side-effects of the menopause, such as hot flushes and night sweats - and there is a large body of evidence that shows it is an effective and safe treatment for most women.
"We would urge patients not to be alarmed by this research - as the researchers state, any risk is extremely low - and if they are currently taking HRT, to continue doing so as prescribed by their doctor. "
However, she said there were risks with any medication and it was important that women were aware of them.
"To minimise any risk, best practice for most women is to prescribe the lowest possible dose of hormones for the shortest possible time in order to achieve satisfactory relief of symptoms," Prof Stokes-Lampard said."

[slacker]

I'm delighted that the Royal College of GPs is taking a rational response to the study results, especially by showing the small number of women who would possibly be affected per year. Thanks for sharing.

As far as types of hormones used, the article states

The regimens of systemic hormone therapy in Finland contain exclusively estradiol, which is given either orally (90%) or transdermally (10%). The regimens identified by trade names were transformed into doses of estradiol (oral or transdermal). Various progestogens were used in combination with estradiol (that is, oestrogen-progestogen therapy), of which norethisterone acetate and medroxyprogesterone acetate were the most common.

[jerryb]

Sorry to add complications but my wife (78) was put on HRT by Bredesen Practitioner . About four months in she had a very bad reaction with swollen ankles, lethargy, and more gut problems on top of her ongoing IBS type C. It had to be either the HRT or the Bredesen supplements and wlhen these were discontinued the symptoms slowly improved but I don’t think she has returned to previous level physically or cognitely. ( MOCA going from range of 19 to 23 down to 16 supports my impression. ) Have had to discontinue protocol and have only staying in ketosis left as hope.

[Orangeblossom]

On the BMJ article it is useful to read the comments by experts on it, for example here...

"There are different types of HRT. This study did not differentiate between oral or transdermal oestrogen nor did women take micronised progesterone8. Transdermal oestrogen and micronised progesterone are optimal types of HRT for women.

In addition, there is increasing evidence to support the use of testosterone in menopausal women as part of their hormone replacement therapy. Testosterone replacement in women has been shown to exhibit neuroprotective effects within the brain, including protection against oxidative stress, serum deprivation-induced apoptosis and soluble β-amyloid toxicity9."

https://www.bmj.com/content/364/bmj.l66 ... -responses

Also the mention of APOE4 and selection bias as well.

[slacker]

Sorry to add complications but my wife (78) was put on HRT by Bredesen Practitioner . About four months in she had a very bad reaction with swollen ankles, lethargy, and more gut problems on top of her ongoing IBS type C. It had to be either the HRT or the Bredesen supplements and wlhen these were discontinued the symptoms slowly improved but I don’t think she has returned to previous level physically or cognitely. ( MOCA going from range of 19 to 23 down to 16 supports my impression. ) Have had to discontinue protocol and have only staying in ketosis left as hope.

I'm sorry to hear of the difficulties you and your wife have experienced. Since cognitive decline is considered an emergency, practitioners typically start multiple treatments at the same time. And as I'm sure you know, multiple issues can be cause memory loss, so more than one intervention is needed for best results. Unfortunately, when side effects occur, it's difficult to know which of the interventions has caused them. Deciding what to do next is a hard decision.

[Julie G]

Great discussion of the recent Finnish study, Orange & slacker. A member of our Facebook community found a similar Finnish study that came to the opposite conclusion. Nothing is black and white for us. Bioidenticals are used exclusively in Finland, but 90% of those used in this latest study were oral. Oral estradiol is associated with increased C-reactive protein and more viscous blood (clotting) both of which are also associated with AD. I can't help but wonder if that confounded things...

[Surupe]

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?

[NF52]

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 brain fog is leaving you feeling awful and hopeless. That is no way to go through life at any age!

One of the great tools of this site is the ability to do Searches, including advanced searches. Here is the result of a quick search using the terms "testosterone + menopause". If you click on the individual posts, then use the "back" arrows to get back to the list use should see some of the discussion on this topic.

Testosterone + menopause search results

Here's the section of the "How-To" wiki on doing searches: Searching for information

You also can just click on the magnifying glass icon in the row of icons next to your user name in the upper right of your screen to start a new search. There is a ton of lived experience and wisdom in those old posts!