Hormone Replacement Therapy E4 Women

[Julie G]

You can find Dr. Hathaway's talk with us here. Apologies for the technical issues that seem to plague us . Here's another powerful PowerPoint from her.

[Orangeblossom]

Orangeblossom, the current best summary is Anne Hathaway's lecture to us at our San Diego meetup last year. Its on our apoe4.info channel on youtube. Her slides are attached to the HRT section of the primer.
Youre asking all the right questions that we have discussed as a group and with Anne. To get up to speed with the current science and where we are as a group, you'll need to read/watch this first.
If you look at Announcements and Events/Stavia's report on San Diego meetup, youll see my notes on her lecture. I think Ive linked the slides there too.

So... the bottom line is that the current best neuroprotective HRT is 17 beta oestradiol transdermally plus cycled micronised progesterone either orally or transdermally or even vaginally, in a dose sufficient to maintain endometrial protection if there is a uterus.
Because many many reasons.
The most compelling for me is the APP cleavage.
The WHI was deeply flawed.

Sent from my SM-G930F using Tapatalk

Thanks for explaining and your patience with a relative newbie. I'm just catching up on things I see. I'll have a look at that and try to stop worrying about the oestrogen receptor polymorphisms, not much can do about them anyway. But may be something to do to tackle the issue.

[Stavia]

Orangeblossom, you are learning stuff at an astonishing rate! We are all very impressed

Sent from my SM-G930F using Tapatalk

[Julie G]

Agree! I'm beyond impressed with your understanding of the E4 allele and how quickly you've progressed. Your inquisitiveness has led to very similar paths in your thinking as those of us who've been working on this for years. Keep asking questions. IMHO, educating yourself is the best innoculation against E4 pathologies. it'a much easier to sustain long term lifestyle changes once you understand the underlying mechanisms.

[circular]

Here are two podcasts with Dr. Hathway I posted elsewhere recently. These are my personal favorites. Some material overlaps but they're also a bit different, so I found it useful to listen to both. If I had to pick one it would be the second, I think ... hard to decide.

Evolving Past Alzheimer's Podcast

NourishBalanceThrive Podcast

[Orangeblossom]

In the news today

https://www.thetimes.co.uk/article/hrt- ... -79ncztbv0

"Hormone replacement therapy patches used to reduce symptoms of the menopause may preserve the brain and protect against Alzheimer’s disease, research suggests.

Over seven years, treatment with the skin patches was associated with less age-related shrinkage of the part of the brain involved with memory, thinking and reasoning.

Women whose brains responded in this way were also less likely to have a hallmark of Alzheimer’s disease. Their brains contained fewer sticky clumps of beta-amyloid, a toxic protein fragment believed to trigger the death of neurons. But hormone replacement therapy had no impact on scores in thinking and memory tests, according to the study published in the journal Neurology.

Kejal Kantarci, the lead researcher from the Mayo Clinic in Rochester, Minnesota, said: “We found that one form of menopausal hormone therapy taken soon after menopause may preserve brain structure in the portion of the brain responsible for memory and thinking skills. It may also reduce the development of amyloid plaques that can build up and lead to memory loss.”

He added: “More research is needed to determine the biological reasons behind brain changes during menopausal hormone therapy.”

also http://www.dailymail.co.uk/health/artic ... imers.html

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK, said:
“There is ongoing research into the role that hormones might play in diseases like Alzheimer’s, but previous studies into the effects of hormone therapy have been mixed. This small study found no link between mHRT and memory and thinking, but women who had taken the hormone estradiol via skin patches showed some signs of better brain health."

Link to the article here

http://n.neurology.org/content/neurolog ... 5.full.pdf

Objective The effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health.

Methods Participants (aged 42–56 years; 5–36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B–PET (n = 68).

Results Ventricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo.

Conclusions The effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain.

Looks like more evidence for the use of patches, then. Which is good, as my friend was just prescribed some and it had a warning on the leaflet saying not to be used in older women (over 65 I think) due to increased risk of dementia.

[Orangeblossom]

Thought this was interesting. It's a comment on previous older research about HRT and is about zinc being affected by it. I hadn't heard of that before.
http://www.bmj.com/rapid-response/2011/ ... redictable

"I commented that increases in dementia were likely because exogenous
hormones can induce zinc deficiency and exogenous hormone use causes the
...pattern of mineral imbalance, lower zinc and higher copper levels.."

But if that were the case wouldn't women have this problem in earlier years when oestrogen levels were higher?

I wonder if it is related to the type of HRT used, as those earlier studies were done with the equine HRT. Is this new to others too? What do you think about it?

There is more on this consultant's experiences with it here.

http://www.bmj.com/rapid-response/2011/ ... deficiency

It would be interesting if this is the case given that zinc to copper ratio is something of importance as we know.

I thought she seemed quite anti-HRT and it seemed contentious as others didn't agree, so went on to try and research it further. I found this

https://www.sciencedirect.com/science/a ... 2X02800037

The risks of disturbances in trace mineral nutrition and metabolism are high following menopause. The aim of the study was to investigate the trace mineral status in postmenopausal women and the influence of hormonal replacement therapy on this status.

"Forty-four healthy postmenopausal women, aged 50–60 years old participated in the study. Eighteen were treated by combined hormonal replacement therapy (HRT) per os for at least two years, and 26 were untreated. Plasma trace mineral levels (Zn, Se, Cr, Mn, Cu), red blood cell antioxidant enzymes (Cu-Zn SOD, Se-GPX, Cu), urinary Zn, Cr, Mg, and Ca excretion were measured. Zinc, selenium and manganese plasma levels, activities of Cu-Zn-SOD and GSH-Px in erythrocytes were not statistically different between the two groups. The percentage of zinc plasma levels below the cut off of 10.7 μmol/L was higher in HRT treated group than in untreated one, whereas zinc excretion was reduced. Plasma copper concentrations were higher in women treated by HRT, whereas erythrocyte copper levels were not modified. Plasma chromium concentrations were significantly higher in women receiving HRT and urinary Cr excretion was decreased. The HRT group also exhibited lower losses of urinary zinc and magnesium than untreated women. These data suggest that hormonal replacement therapy provides beneficial effects on trace mineral status related to menopause."

Firstly, not sure why they think it's beneficial to have higher copper and lower zinc, but it seems it may have some effect on these. Apologies if this has been discussed before. I couldn't find anything on it when I searched. Might have some implications for us. Unless it is something liked with the equine form of HRT. Unfortunately it isn't possible to tell which type they used due to just the abstract being available.

Even if it did cause such problems I don't think it would be put me off taking it as seems beneficial. I wonder if might be something to keep an eye on though in light of this? Not sure.

[rrmolo]

N equals one. Me. 4/4. Now 78. Had ovarian CA at age 41 and my GYN did not want me on estrogen. Went through surgical menopause cold turkey. Still doing fine but now take a pea size drop of premarin at bedtime. I used to worry about that but looking back it probably didn't make any difference.

[Orangeblossom]

N equals one. Me. 4/4. Now 78. Had ovarian CA at age 41 and my GYN did not want me on estrogen. Went through surgical menopause cold turkey. Still doing fine but now take a pea size drop of premarin at bedtime. I used to worry about that but looking back it probably didn't make any difference.

Do you think you could get one of the patches instead? It seems they might work better that Premarin. Kind thoughts

[slacker]

Dr Ann Hathaway has shared some additional studies that she has started to include in her most recent bHRT presentations. Unfortunately, the full articles are behind a pay wall. I am providing links to the abstracts, and my interpretation of the full texts (one at a time).

Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality
Link to abstract

This study looked at the risk of death from coronary artery disease, stroke, and all cause mortality with estradiol use in Finnish women. While the reduction in deaths in estradiol users was statistically significant, the absolute reduction of death may not be clinically significant in my opinion. However, increased risk was not found.

The authors acknowledge the possibility of healthy woman bias in any observational study, and that their findings show an association between hormone therapy and reduction of death, and do not prove causality.

Most of the women were on oral estradiol, not topical, and still had less mortality. Other studies have shown increased ischemic stroke, DVT (deep vein thrombosis), and PE (pulmonary embolism) on oral estradiol. Links to these studies are on page 40 of this thread. These studies were not looking at an endpoint of death, so the findings may very well be compatible.

The Finnish study linked above showed that risk reductions were comparable in women initiating hormone therapy before age 60 years and at age 60 years or older. This implies that the benefits of hormone therapy may not be limited to a specific window of opportunity in post menopausal women, as theorized.