I’m surprised and confused by several things you said.
Why women are protected from MS relapses during pregnancy? The level of estrogens goes down as protection from abortion (biological common sense)
Did you really mean to say the level of estrogens goes down or was that a mistake maybe? The information I’ve read about the Phase I estriol trial was that the dose (8 mg) was based on estriol levels during the last 3 months of pregnancy, so I definitely thought estriol levels were at their highest level during the last trimester of pregnancy when disease activity “lessens”.
The Phase I estriol trial, albeit a very small one, did significantly decrease the number and size of inflammatory brain lesions, improve cognitive test scores, and decreased “black holes”, i.e. “areas of myelin damage identified during the study did not evolve into severe black holes”
in women with RRMS. Here’s one of the original news releases about it.Pregnancy Hormone Estriol Shows Promise As Multiple Sclerosis Treatment In First Human Trials
and this is a more recent one--Could Estriol Be The Elixir For Multiple Sclerosis?
Of course progesterone and Vitamin D3 levels are also higher during the third trimester and drop rather dramatically post delivery as well.
Could it be that the drop in estriol (a form of estrogen), progesterone and Vitamin D3 levels in the 3 months post partum contribute to the increased MS disease activity and “relapses” during that time period? Or, maybe it's something that we don't even know about yet?
The articles also indicate estriol is used for menopausal symptoms in Europe, so I’m curious as to why you’re so opposed to it for that purpose.
As to it's possible role in MS, I think
--the rationale for the estriol trial and the trial itself, combined with
--recent epidemiological research that found that oral contraceptives (which contain both estrogen and progesterone) may delay a diagnosis of MS, i.e., the incidence of MS was 40% lower in women who had used oral contraceptives in the previous three years;
--a recent clinical trial that found the EDSS score was about 25% lower in oral contraceptive users prior to treatment than never-users, and,
--the pre-clinical neuroprotective properties of estrogen
all seem to support the idea that estrogen has the potential to be beneficial rather than detrimental to people with MS. Much more research is needed of course.
More importantly though, at least to me, than a focus on relapses, is that the natural history of the disease is more or less as Cure O indicated and you agreed (I think) and that is that the vast majority of people with RRMS transition to a SPMS course and increasing disability, without relapses, after some period of time.
What I think may be a factor that’s been overlooked is that several hormones, including estrogen, all of which display significant neuroprotective properties (at least in pre-clinical research), also are on the decline during the period of time that people transition from RRMS to SPMS.
Menopause itself is just a point in time. DHEA, testosterone, progesterone and estrogen levels all decline, some rather significantly, well before menopause. DHEA for example declines most significantly between the ages of 20-40 when most people are diagnosed. I think progesterone levels also start to decline before there’s a significant drop in estrogen.
So, it seems to me the gradual decline of several hormones with “neuroprotective” properties, which occurs during the aging process, very roughly
coincides with and parallels the transition to SPMS and increased disability. Thus, the question becomes, does the loss of this neuroprotection with aging as a result of declining hormones levels, make everyone more vulnerable to neurodegeneration and neurodegenerative insults, and for people with MS, increasing disability over time?
There was this recent research: Progression in multiple sclerosis: Further evidence of an age dependent process
Our data give further support to the notion that progression in MS is an age dependent process independent of relapses.
Taking it out of the realm of sex steroids, here’s some recent research that I think illustrates the point. This research is on Vitamin D, which also declines with age. Head’s up Legs and Finn
(it’s from Finland ). Neurosteroid hormone vitamin D and its utility in clinical nutrition
In both animals and humans, vitamin D serves as an important endogenous and/or exogenous regulator of neuroprotection, antiepileptic and anticalcification effects, neuro-immunomodulation, interplay with neurotransmitters and hormones, modulation of behaviors, brain ageing, and some other, less-explored, brain processes. SUMMARY: Vitamin D emerges as an important neurosteroid hormone in the brain, with a strong potential for age-specific applications…..
Long post I know. You all know I couldn't let it "rest". I remain ever optimistic about the potential of hormones to help manage MS. Tony, I think it's clear I really don’t understand your total opposition to estrogen and would certainly welcome more information about that.
Take care all.