Hormone Replacement Therapy E4 Women

[Lucy5]

I'm wondering if I misread the study. The women participating in the KEEPS Trial conducted from 2006- 2011 were 5 to 36 mos past menses. The neuroimaging (quote below) took place over the following 3 years after KEEPS. So I understood that to mean the women in the current study would have been a minimum of 6 1/2 to 9 years past menopause?

Neuroimaging for the current study was conducted from December 2012 through July 2014 and included the subsample of women who were enrolled in KEEPS at the Mayo Clinic, to investigate the effects of the KEEPS hormone treatments on Aβ deposition three years after the end of the trial.

[Stavia]

Yes but its timing of the INITIATION of the HRT that is thought to be crucial, not the duration.
It is hypothesized that initiation soon after oestrogen drop is neuroprotective and there is an as yet undefined time, after which initiation of HRT may not confer a neuronal benefit. The reason for this is that there may be complex permanent brain changes after some years of low oestrogen.

[CatDC]

I've been on oral HRT (estradiol and medroxyprogesterone). After looking at the study, I'm wondering if I should ask my ob/gyn to switch me to the patch. Any thoughts on this?

[circular]

I find it interesting that it helped when starting soon after formal menopause. I started HRT before formal menopause because my premenopausal symptoms were so bad, but I think I had been in premenopause for a good four years or so before getting the HRT.

I wonder, if they looked in a much larger study also at years in premenopause without HRT while estrogen is on an extended roller coaster ride, if women who have a longer premenopause are less responsive due due years of continuous ups and downs of estrogen. I think they'd be remiss not to look into this end of the spectrum too, because a lot of women are a downright mess during a prolonged premenopause. I'm not sure if there's a technical definition for when premenopause has started or if it's too subjective to pin down.

[Lucy5]

Thanks for the clarification, Stavia. I totally missed the point that this study doesn't tell us anything regarding the impact of starting HRT outside the 5-36 mos window; was too busy focusing on the possible benefits...(and seeing what I wanted to see, I suspect!)

Beyond that, when I took another look at the KEEPS description of study participants, it describes them as between 5-36 months past their last menses, not menopause. Yet Table 1 of the current study labels the participants past "menopause" with the E4 Estradiol group an average of 18 mos into that window. So even a bit more unclear, perhaps, as to ideal timing, but starting HRT earlier in the menopause process (taking into account other relevant health risks) would probably get my vote at this point.

[Stavia]

Lucy, well spotted. The thing is that "menopause" is an arbitrary definition as oestrogen does not suddenly one day switch off. I don't think anyone knows at what oestrogen level trophic support of the brain is significantly compromised. Of course gynaecologists will have their favourite blood level to target but this is just their opinion.
All we have to go on is symptoms: hot flushes, atrophic genital mucosa, and of course cessation of menses. Arbitrarily a year after the last period is a nice clean benchmark.
I started HRT 8 months after my last period but I never had any hot flushes, however I had genito-urinary mucosal symptoms quite a while prior. I was congratulating myself on a painless transition - then I suddenly had sleep disturbance at the 8 month mark. Everyone is different.

[TheBrain]

My FM MD gave me a PDF of the following review article. I did a couple of searches on the forum and couldn't find it so thought I'd post the Pubmed link and the abstract.

The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?
http://www.ncbi.nlm.nih.gov/pubmed/19179815

Abstract
BACKGROUND:
The use of bioidentical hormones, including progesterone, estradiol, and estriol, in hormone replacement therapy (HRT) has sparked intense debate. Of special concern is their relative safety compared with traditional synthetic and animal-derived versions, such as conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), and other synthetic progestins. Proponents for bioidentical hormones claim that they are safer than comparable synthetic and nonhuman versions of HRT. Yet according to the US Food and Drug Administration and The Endocrine Society, there is little or no evidence to support claims that bioidentical hormones are safer or more effective.

OBJECTIVE:
This paper aimed to evaluate the evidence comparing bioidentical hormones, including progesterone, estradiol, and estriol, with the commonly used nonbioidentical versions of HRT for clinical efficacy, physiologic actions on breast tissue, and risks for breast cancer and cardiovascular disease.

METHODS:
Published papers were identified from PubMed/MEDLINE, Google Scholar, and Cochrane databases, which included keywords associated with bioidentical hormones, synthetic hormones, and HRT. Papers that compared the effects of bioidentical and synthetic hormones, including clinical outcomes and in vitro results, were selected.

RESULTS:
Patients report greater satisfaction with HRTs that contain progesterone compared with those that contain a synthetic progestin. Bioidentical hormones have some distinctly different, potentially opposite, physiological effects compared with their synthetic counterparts, which have different chemical structures. Both physiological and clinical data have indicated that progesterone is associated with a diminished risk for breast cancer, compared with the increased risk associated with synthetic progestins. Estriol has some unique physiological effects, which differentiate it from estradiol, estrone, and CEE. Estriol would be expected to carry less risk for breast cancer, although no randomized controlled trials have been documented. Synthetic progestins have a variety of negative cardiovascular effects, which may be avoided with progesterone.

CONCLUSION:
Physiological data and clinical outcomes demonstrate that bioidentical hormones are associated with lower risks, including the risk of breast cancer and cardiovascular disease, and are more efficacious than their synthetic and animal-derived counterparts. Until evidence is found to the contrary, bioidentical hormones remain the preferred method of HRT. Further randomized controlled trials are needed to delineate these differences more clearly.

[circular]

Wow, thanks for this update. The first OB/GYN who prescribed my compounded hormones was big on estriol, but I'm not sure why. My Biest cream is 50% estradiol and 50% estriol. I've sometimes wondered if I'm getting enough estradiol and what the estriol is doing. She did mention she thought less risk of breast cancer with it. That was about 4-5 years ago.

[Silverlining]

I started hrt literally two weeks after my last period August last year. Somehow, I just knew that was my last cycle and it was! Kinda crazy that I knew that. So I started with the biest cream but it did not work for me as my estradiol serum levels dropped continuously to undetectable in five months. I switched to the patch and levels doubled, then tripled within 8 weeks. My last estradiol level was like 108 a few months ago. I need to retest soon to be sure I'm not too high. I feel really good though, no more 20 plus hot flashes a day! As a 4/4 starting hrt at the actual menopause start, I'm a good candidate for their study...maybe I should contact them lol.

[Stavia]

Question for the team.
Have a new patient 3/4. Some symptoms of SCI. 57 years old. Menopause age 50, sailed through it. 20kg overweight. Insulin resistance. Raised homocysteine. Low D3. Gonna sort all the things and throw the whole protocol at her BUT to HRT at this stage 7 years later or not to HRT?