Hormone Replacement Therapy E4 Women

[circular]

I finally got around to reading this paper last night. Some standout passages for me were:

In cultured rat hippocampal neurons … Exposure to a low concentration of 17B-estradiol promoted neuronal survival and intracellular calcium homeostasis, whereas exposure to a high concentration was ineffective and resulted in increased cellular vulnerability to neurodegenerative insults.

This may relate to, I think it was Dr. Brinton's mention, that we can get too much estrogen; i.e., not to assume that "optimal" (Bredesen's protocol) is high end. This may be tricky for those not getting more specific advice as to our target estradiol levels during and after perimenopause by not being in the study or a customer.

Progesterone does not seem to have the same neuronal effects and, in many instances, antagonized the neural actions of estrogen in both preclinical and clinical analyses.

This is no surprise, but the ratio is going to be important. Again, those of us not getting specific guidance from Drs. Bredesen and Brinton are a bit in the dark as to "optimal" target. I truly understand Dr. Bredesen and his study subjects not sharing the details of his protocol, but this one seems VITAL to us all! We need SOME guidance! These targets seem to me would be more or less the same for all of us? Of course everyone should work within the context of other risk factors they may have, but a starting point? And yes, probably more studies need too be done to tweak the targets, but something, please please please?

As neither cholesterol nor long-chain fatty acids can pass through the blood-brain barrier, an increase[d] fatty acid metabolism in the brain is indicative of increased catabolism of brain-derived lipids, which can disrupt cell membranes and lipid-rich reservoirs, such as myelin, in the brain.

Okay, geez, now, if we get more ketone bodies into our brain through diet and/or supplements, will the increased fatty acid metabolism in the brain start gobbling those and leave our cell membranes and lipid-rich reservoirs alone, or will it just gobble both? Naturally maybe no one knows, and maybe "it all depends", again.

I didn't have a pen when reading the whole hypometabolism section, so need to go over it again and find my standouts there.

Question: Have the studies on ApoE4 showed that everyone with one or two 4s hypometabolizes glucose, or is it a tendency offset in some of us by other factors? The only study I saw on this only had 12 people in it, but I gather there is more data on it than that.

[Julie G]

Great questions, Circ. I wish I had answers...

On the hypometabolism, it appears to be all E4 carriers in a dose dependent fashion starting as early as our 20s and 30s. That being said, I see some 4/4 women here (Stavia & Lilly are good examples) that appear to have other protective mechanism at play. I also see other 4/4 women, like myself (15 hot flashes/flushes an hour accompanied by cognitive decline , ) that are dramatically affected by the cerebral hypometabolism.

I agree with Lilly. This paper is HUGE- groundbreaking for ur population. Dr. Brinton is surmising that the cerebral hypometabolism, that accompanies the E4 allele (and is also present in aging, IR, PCOS) could account for the differences in gender manifestation of Alzheimer's in our population. W.O.W. That gives us an opportunity to intervene in symptomatic women and perhaps an opportunity to be pro-active in non-symptomatic women.

[circular]

Not sure if this has been linked. The Alzheimer's Drug Discovery Foundation website (someone associated with it is a member here), has this page on their website about HRT and the brain. I need to get off the computer for a while, but I noted a section discussing HRT and E4. It references a number of different studies, some discussed here and probably some not yet discussed here. It's not overly optimistic, maybe even a little pessimistic, but at least supports our notion that intervening with HRT around the menopause (in women without contraindicated risk factors) may help for a time. It reminds me that we have no long term studies on HRT using bioidenticals in ApoE4 women, I don't think? So for now I'm comfortable using it, but when it's time to reassess not enough time will have elapsed for the science behind it to have been vetted

http://www.alzdiscovery.org/cognitive-v ... ne-therapy

[Stavia]

Agreed. I plan to take hrt for 5 years then reasess

[circular]

Not only will not enough time have elapsed in five years for good longitudinal studies, I wonder if any HRT studies including genotypes are based on bioidenticals. I doubt that, and not likely to happen soon. Maybe Brinton's crowd can be convinced to at least to petri dish studies of brain tissue/neurons (or whatever would be needed) and bioidenticals vs. a standard pharma synthetic. Maybe Dr. Brinton could be hooked in with us in a Q&A thread or some such thing?

[Stavia]

Ooo now that's a good idea. Guest on the forum. Julie?

[Julie G]

I'll ask. She's previously expressed interest in coordinating a possible study with us...

[circular]

Let's not forget the need for research to be on bioidenticals too, as we communicate with her. I'm sure because synthetic are more widespread they feel studying that may impact more women, but we need the truth about bios. Testing only one form does nothing for overall clarity. If the results are negative benefit we still need longitudinal for bios. All studies should have control, synthetic and bio. There's not time to waste on only looking at synthetics as has been the tradition (although I'm unaware of what Dr Brinton's studies have covered).


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[Julie G]

Dr. Brinton is VERY focused on how lack of estrogen promotes cerebral glucose hypometabolism and how that interplays with E4 women who already have a deficit. She believes that this phenomenon accounts for the gender difference in E4 conversion to Alzheimer's- HUGE.

My guess is that all research moving forward will be on bio-available HRT. Are synthetics even used anymore? Previous research used synthetics because that is what was primarily used.

[circular]

Can't say for sure. I was under the impression that overall women are being told not to use HRT of any kind based on the studies using synthetic versions. I had the impression that rather than turning to bioidenticals, many doctors are instead turning to 1) encouraging lifestyle changes (a good but not sufficient step for many women needing extra help who don't have contraindications) and 2) antidepressants, which I see as just horrible. Of course if a woman needs an antidepressant it may be useful, but I think many doctors are seeing mood swings and women being overwhelmed and tired affecting their moods as depression, and rather than prescribe BHRT they prescribe antidepressants. Of those prescribing BHRT, some are prescribing FDA approved bioidentical HRT while many if not most doctors are still leery of compounded versions. I appreciate what their concerns are but I haven't felt they were justified given a decent compounder. I'm not sure what the research says, if anything, comparing FDA approved BHR forms with compounded forms. It seems to me most are just discouraging compounding pharmacies and want it all to be FDA approved. If it works I'm good with that. I really haven't seen anything on all this. It's just been my "impression", partly from hearing what others have been told.