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Hormone Replacement Therapy E4 Women

Posted: Wed Nov 27, 2013 11:05 am
by Silverlining
Edited 3/16/2014 to include two recent studies:

New study focusing on women at risk for AD and Estradiol:

Prospective Randomized Trial to Assess Effects of Continuing Hormone Therapy on Cerebral Function in Postmenopausal Women at Risk for Dementia ... ne.0089095

Study focusing on estrogen associated polymorphisms and risk of AD:

Estrogen associated gene polymorphisms and their interactions in the progress of Alzheimer's disease.

Original Post:

Accelerated Cell Aging in Female APOE-ε4 Carriers: Implications for Hormone Therapy Use ... ne.0054713

"In sum, this study represents the first longitudinal demonstration of accelerated cell aging in APOE-ε4 carriers. Our finding that even high-functioning, healthy mid-life women with the ε4 allele bear markers of cellular aging suggests the need for further research to understand the potential utility of leukocyte TL as an early indicator of future dementia risk. These data provide strong evidence that the impact of the APOE risk allele on telomere attrition begins in the absence of, or prior to, clinical and behavioral evidence of dementia. Futher, the data provide initial evidence that hormone therapy, begun at the onset of the menopausal transition, might buffer against TL attrition in women at risk of cognitive decline. Importantly, terminating HT had beneficial effects for non-carriers, indicating that HT may have differential effects on cell aging across genotypic subgroups. Going forward, it will be crucial to extend these initial data to a larger epidemiological sample to systematically probe whether specific HT formulations, timing of initiation, and duration of use differentially impact cellular aging."

And for those of us who have Factor V Leiden Blood Clotting Disorder some research suggests much less risk with transdermal HRT:

Factor V Leiden Thrombophilia

"Some evidence suggests that the thrombotic risk from transdermal HRT is lower than the thrombotic risk from oral preparations, in women with and without prothrombotic mutations [Scarabin et al 2003, Straczek et al 2005, Canonico et al 2007]. In one study, women with factor V Leiden who used oral estrogen had a 16-fold higher risk for VTE than non-users without the mutation. In contrast, the thrombotic risk in women with factor V Leiden who used transdermal estrogen was similar to that in women with a mutation who did not use estrogen. Among women with factor V Leiden, the use of oral estrogen was associated with a fourfold higher risk for VTE than transdermal estrogen [Straczek et al 2005]. However, there are no prospective trials confirming the safety in women with thrombophilia and/or prior VTE. "

EDIT 1/6/2014 to add new research below (Just what we E4 women need, more ambiguity :( )

APOE modulates the effect of estrogen therapy on Aβ accumulation EFAD-Tg mice ... 4013011130


The interactive effects of APOE and ERT after OVX on Aβ accumulation were determined in EFAD mice.

ERT decreased extracellular amyloid plaque and Aβ deposition with APOE2 and APOE3.

ERT increased extracellular amyloid plaque and Aβ deposition, but lowered soluble Aβ42 with APOE4.

First in vivo evidence that hAPOE differentially regulates the effects of ERT on Aβ deposition.

Aβ42 levels may be a critical read-out for APOE4 carriers enrolled in ERT trials."

Postmenopausal Hormone Therapy, Timing of Initiation, APOE and Cognitive Decline


Compared with never users, past or current HT users showed modest but statistically significant worse rates of decline in the TICS: the multivariable-adjusted difference in annual rate of decline in the TICS among current estrogen only users versus never users was −0.04 (95% CI = −0.07, −0.004); for current estrogen+progestin users, the mean difference was −0.05 (95% CI = −0.10, −0.002). These differences were equivalent to those observed in women who are 1–2 years apart in age. We observed no protective associations with early timing of hormone initiation. We found suggestive interactions with APOE e4 status (e.g., on TICS, p-interaction = 0.10), where the fastest rate of decline was observed among APOE e4 carriers who were current HT users."

Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice

"To our knowledge, this is the first investigation of presynaptic density in aging female apoE4 and apoE ko mice. We found a decrease in presynaptic density in the hippocampus of middle-aged female apoE4 mice compared with WT mice. This may be the result of a specific harmful interaction of estrogen with apoE4, as we did not observe any differences in male mice. In addition, we found neurogenesis to be increased in middle-aged female apoE ko mice. Previous studies have suggested a compensatory mechanism for synaptic failure by temporarily increasing the number of synaptic contacts and/or neurogenesis. The trend of increased neurogenesis found in female apoE ko mice in our study supports this hypothesis. Our results support the previously determined sex-specific differences observed between APOE genotypes, which could account for some of the sex differences in AD and CVD. Sex differences should be taken into account in any research concerning CVD, AD, or apoE. "

Possible APOE Genotype and Sex Dependent Effects of 17-α- estradiol on Alzheimers Disease Pathology ... ?aid=21433
This is an editorial suggesting 17-β-estradiol (β-E2) and in particular its precursor 17-α-E2 therapy could be beneficial for both men and women.

Re: Hormone Replacement Therapy E4 Women

Posted: Wed Dec 18, 2013 11:04 am
by Julie G
Effects of gender and menopausal status on the association of apolipoprotein E phenotype with plasma lipoprotein levels. Results from the Framingham Offspring Study.

CONCLUSIONS: "The lower frequency of the e4 allele in older subjects, which is more evident in women than in men, could be related to the stronger impact of the E isoforms in postmenopausal women than in older men. Our results indicate that the sharp increase in LDL cholesterol levels occurring in women after menopause may be accentuated by the presence of the E4 isoform. In fact, menopause in women with the E3/2, E3/3, and E3/4 phenotype was associated with a 9%, 21%, and 26% increase, respectively, in LDL cholesterol levels.

COMMENTS:It is remarkable how similar E4 lipids are to other genotypes in this older observational study, UNTIL it comes to post-menopausal women. Then, we see a dramatic jump in both LDL and Apo-B. This could be the basis of a strong argument for E4 women to use HRT therapy if possible.

Re: Hormone Replacement Therapy E4 Women

Posted: Wed Dec 18, 2013 3:45 pm
by SpunkyPup
High and Low Cholesterol in the Light of Hormonorestorative Therapy ... 0615507441

Re: Hormone Replacement Therapy E4 Women

Posted: Thu Dec 19, 2013 5:33 am
by Schnooks
Great! Looks like I need to be worried now that I'm post-meno and not on any hormone therapy

Re: Hormone Replacement Therapy E4 Women

Posted: Thu Dec 19, 2013 7:53 am
by Gina99
About 2 years ago I didn't know I was technically in menopause (base on FSH levels), I went to my ob/gyn and said, I think I am very sick. I explained all my symptoms and after all blood work it was determined to be menopause. I absolutely had to go on HRT then. I was having excessive fogginess, cognitive issues, and felt physically ill (like a really bad case of the flu) and started on an estradiol. I actually almost quit my job it was so bad. I had immediate results and do not regret the decision at all. I was fine the year before, and then bam down for the count. So there is something going on I think relative to the protective effects of estradiol BTW I am a 3/4.

Re: Hormone Replacement Therapy E4 Women

Posted: Thu Dec 19, 2013 8:27 am
by Julie G
Me too, Gina. When my hormone levels dropped, I felt VERY unwell- almost unable to leave my house. I'm a 4/4. Once I began HRT, I felt amazing; a night and day difference.

Schnooks, any specific reason why you aren't on HRT? We have a few members here who carry genes for Factor V and their docs have STILL recommended HRT. There is evidence that E4 women experience shortened telomeres post-menopause without HRT. (Telomere length is associated with longevity.)

The medical establishment has been all over the place with their recommendations, but now (with bio-identical hormones) have come to the conclusion that balanced HRT (estrogen end progesterone) IS beneficial for most women. And, our subset MAY need HRT more than others.

It's never too late to start. My 76 y/o (most likely 3/4) Mom just started at age 76. She is AMAZED at how much better she feels. She had major insomnia issues that are now rectified. She's dropped 3-4 prescription meds just by supplementing natural hormones. There are definitely risks starting that late, but she and her doc carefully weighed them out and the results have been profound.

Posted: Thu Dec 19, 2013 10:52 am
by Schnooks
I haven't need HRT as far as I know.. but maybe I do and just don't know it.
I just find this all overwhelming with all the lifestyle changes needed to try to survive as a 4/4 !
I guess I have to get my levels tested at some point.. not gonna happen anytime soon right now.

Re: Hormone Replacement Therapy E4 Women

Posted: Thu Dec 19, 2013 11:18 am
by Julie G
I's a lot to take in. You're still young and may not need HRT for a while. My guess is that you'll know when you need help :shock: The symptoms were VERY severe; kinda happened overnight for me...with years of lesser symptoms leading to a crash.

The good news is that you're aware of the benefits of HRT for E4s and will be prepared when you need help.

Re: Hormone Replacement Therapy E4 Women

Posted: Thu Dec 19, 2013 12:46 pm
by SpunkyPup
I have way to high testosterone and there is none here who treats it.. some tests not available. ... -hormone-/

Re: Hormone Replacement Therapy E4 Women

Posted: Thu Dec 19, 2013 1:42 pm
by Starfish77
age 76 E4/E4 treated for BREAST CANCER with ESTROGEN RECEPTORS in 1980-81 internal "seed" radiation implants for three days/five weeks conventional radiation/one year chemotherapy ----told never to take or use estrogen

I was treated for breast cancer with chemotherapy and radiation at age 43. My ovaries disappeared. I was told my
cancer had estrogen receptors. I was told never to take or use any product containing estrogen.
When I was 69 I had an oncologist who wanted to put me on Arimidex as a future cancer preventive. I did not tolerate
it well. She put me on Arimicin. It was exactly the same. it gave me all the things that I have heard women with menopause get. I just stopped taking it after a few months without asking my doctor. It made my joints hurt at well.
Now it is well known that it causes joint pain.
After I completed chemotherapy I had real short term memory problems. I thought it was only the chemo. Now I
realize it might have been the lack of estrogen as well. I was so concerned about my memory, i had myself tested without using my health insurance because I didn't want the results in my files. I made them promise to destroy the results after they gave them to me. I don't think I did very well. My memory did come back after a couple of years. Back in 1981 doctors did not believe chemo influenced your brain. Since then "chemo brain" has finally become accepted by the medical profession.