Estriol May Help Prevent Relapse in MS and Autoimmune Disorders.

[Annikki]

Research has found that autoimmune disease symptoms decrease in the third trimester of pregnancy. The reason for this is a hormone associated with protecting the fetus from the mother's immune system called estriol. The hormone is now being used to control multiple sclerosis symptoms. Here's some of the press release:

"ANN ARBOR, Mich., Sept. 19, 2011 /PRNewswire/ --Adeona Pharmaceuticals, Inc. (AMEX: AEN), a developer of innovative medicines for serious central nervous system diseases, announced today that the 150th patient has been enrolled in the randomized, double-blind, placebo-controlled, multi-center clinical trial of its Trimesta (oral estriol) drug candidate for relapsing-remitting multiple sclerosis (MS) in women, per the original protocol.

We are excited to announce the enrollment of the 150th MS patient in this clinical trial, achieving our original targeted goal for enrollment. I am also very pleased that we have funds available to continue enrolling additional patients in this landmark MS trial," said Dr. Voskuhl. "Of the 400,000 people in the U.S. afflicted with MS, approximately 85% are initially diagnosed with relapsing-remitting MS, which is characterized by relapses, or attacks of declining neurologic function, followed by periods of remission. As we continue to dose and monitor each MS patient enrolled in the trial over a two year period, we would expect to demonstrate a statistically significant reduction in the rate of relapses in the patients treated with oral Trimesta."

"Completing enrollment in the Trimesta MS clinical trial as originally prescribed in the protocol is a significant milestone for Adeona and for MS patients, as it brings us one step closer to a potential treatment for women suffering from this devastating disease," stated James S. Kuo, M.D., M.B.A., Adeona's Chairman and CEO. "Once all of the patients have been enrolled and dosed for two years, we look forward to announcing Dr. Voskuhl's top-line results, and if positive, we would expect to seek FDA guidance on filing a New Drug Application."

Trimesta (oral estriol) is Adeona's proprietary drug candidate for the treatment of relapsing-remitting MS in women. Estriol has been approved and marketed for over 40 years throughout Europe and Asia for the treatment of post-menopausal hot flashes. It has never been approved by the FDA for any indication in the United States.

It has been scientifically documented that pregnant women with certain autoimmune diseases experience a spontaneous reduction of disease symptoms during pregnancy, particularly in the third trimester. The PRIMS (Pregnancy In Multiple Sclerosis) study, a landmark clinical study published in the New England Journal of Medicine followed 254 women with MS during 269 pregnancies, and for up to one year after delivery. The PRIMS study demonstrated that relapse rates were significantly reduced by 71 percent (p < 0.001) through the third trimester of pregnancy compared to pre-pregnancy-rates, and that relapse rates increased by 120 percent (p < 0.001) during the first three months after birth (post-partum) before returning to pre-pregnancy rates.

http://m.prnewswire.com/news-releas...tiple-sclerosis-clinical-trial-130110268.html

:mask::Retro smile:

 

[Ema]

Has anyone (especially anyone who experienced remission of ME/CFS symptoms during pregnancy) ever tried estriol to see if that effect could be reproduced while not pregnant?

It looks like a minimum dose is 8 mg of estriol/day which is higher than what is typically used for BHRT.

The study for MS completed last January and results were generally positive though I'm not sure why they felt the need to study estriol plus glatiramer. It seems that may have just muddied the waters though perhaps it was necessary to include a high priced pharmaceutical drug in order to get the study funded.

It looks like oral estriol may not be quite as safe as transdermal estriol (no increased risk or cancer compared with no use of hormone) which also makes me wonder why they chose that preparation with all other factors being equal. It's also not clear to me if the increased risk seen after 5 years of oral estriol disappears when it is combined (as it should be) with progesterone.

Of the 83 patients in the estriol group, 70 completed the 1-year study and 60 completed the 2-year study. In the placebo group, which initially comprised 81 patients, 63 completed the 1-year study and 56 the 2-year study.

At 12 months, the estriol plus glatiramer acetate group had a 47% reduction in confirmed relapses compared with the placebo plus glatiramer acetate group (P = .0326; after adjustments for baseline characteristics, P = .0306).

http://www.nationalmssociety.org/Ab...minary-Results-from-Phase-2-Clinical-Trial-of

 

[Hip]

Has anyone (especially anyone who experienced remission of ME/CFS symptoms during pregnancy) ever tried estriol to see if that effect could be reproduced while not pregnant?

I have experimented with taking estriol on a short term basis (for up to 10 days) as a test several times. In my tests, I took 0.15 mg of estriol daily, transdermally applied as a cream on the skin, rather than as oral tablets.

I used Ovestin cream, which has 1 mg of estriol per gram of cream.

Ovestin is intended to be used intravaginally, and 0.5 mg of estriol applied intravaginally is equivalent to 8 to 12 mg of estriol given orally, in terms of the serum levels of estriol achieved.1

However, for guys like myself experimenting with applying Ovestin estriol cream transdermally, it's not clear how much estriol is absorbed through the skin. This study on murine skin found that only 2.45% of estriol absorbed transdermally; whereas this article states (without any references) that 20% is absorbed transdermally. I could not find absorption figures for the intravaginal route to compare.

Nevertheless, I did have some very definite effects from transdermal estriol:

General effects of estriol I noticed:

• Estriol made me a lot less irritable (irritability and grumpiness are known symptom of ME/CFS, but estriol noticeably improved these).
• Estriol made me more sociable.
• Estriol made me engage more in spontaneous, gossipy chatting with people around me.
• Estriol had an antidepressant effect, making me feel a little more happy and contented.
• Estriol increased the amount of saliva in my mouth, improving this dry mouth condition often found in ME/CFS.
• Estriol was beneficial for my ME/CFS chronic sore throat — I found my sore throat was much improved while taking estriol.

I also noticed that this hormone produced a kind of feminization effect on my mind, sort of softening the male mental disposition a little bit. But this was a fairly subtle effect.

These effects of estriol appeared within several hours of applying 0.15 mg of estriol transdermally to my skin, and disappeared within a day or so once I stopped using estriol.

My last experiment with estriol was several months ago, and I plan to repeat this soon, using a higher dose of transdermal estriol, and taking it for a longer time (perhaps taking estriol for one month).



Note that in terms of reducing autoimmunity and inflammation, estriol appears to work equally well in men and women, as this study demonstrated.

However it is likely that if men take high enough doses of estriol for long enough periods, this will start producing some feminization effects on the male body. These feminization effects will likely be very mild, though, because estriol is by far the weakest of the three estrogens in terms of feminization effects. For breast development, I read estriol is 1000 times weaker than the other two estrogens (estradiol and estrone). 1 So if you are a transgender individual wanting to grow breasts, estriol is not going to do much for you physically. However it does appear to have one or two very mild physical effects: one transgender male described the effects of daily 0.25 mg transdermal estriol here: it mostly seemed to produce mental feminizing effects; the physical effects were some nipple enlargement and buttock enlargement (presumably from increased subcutaneous fat).



Here's a study regarding estriol's anti-autoimmune effects: Estriol generates tolerogenic dendritic cells in vivo that protect against autoimmunity.

Some info on Ovestin cream here.

 

[Ema]

I took 2 mg of estriol yesterday and was still a grumpy guts.

Interesting info, @Hip! I saw the Ovestin cream but ended up with this one:

https://www.smokymountainnaturals.c...oducts/P29-paraben-free-natural-estriol-cream

It's got 3.125 mg per 1/4 teas.

The only thing I reallt worry about is if it actually is a Th2 shifter. I seem to finally be having some luck with LDN and the last thing I want is to cancel that Th1 shift out with the estriol. But I'm never sure how much there is to that theory anyway or if it is more dynamic than usually presented in that we are constantly shifting between the two arms.

 

[Hip]

Yes I read that estriol shifts to Th2, but just how strongly it does this was not clear. I understand that pregnancy often can bring some remission to ME/CFS symptoms, so this suggests the overall effect of estriol is beneficial to ME/CFS.

This paper said:

A pregnancy has protective effect on Th1-mediated autoimmune diseases, and a deteriorative effect on Th2-mediated autoimmune diseases. Numerous studies, both experimental and clinical, imply that estriol and progesterone, at high doses (such as those achieved during pregnancy), have potent anti-inflammatory and neuroprotective roles.

It could be the anti-inflammatory effects of estriol that benefit ME/CFS patients during pregnancy.

 

[Hip]

I took 2 mg of estriol yesterday and was still a grumpy guts.

You might try a lower dose, say 0.2 mg, and see how that feels. It might take a few days for your current dose to leave the system though.

 

[Ema]

You might try a lower dose, say 0.2 mg, and see how that feels. It might take a few days for your current dose to leave the system though.

I think the half life of estriol is really short - something along the lines of an hour.

I'm not sure about a lower dose, especially as a woman. I feel like women might need even higher doses to compensate for having more of the stronger estrogens around. I was aiming for the 8 mg that was used in the study.

Estriol can also lower MMP-9. Shoemaker says high levels are found in mold injured patients. My MMP-9 level is just above his "normal" range at 464 (85-332).

And also, estriol looks like it can inhibit the microglia as well.

Further revelations about E3 and its potential benefits were noted by researchers reported on a study analyzing mouse microglia (CNS immune defense function).28 It was observed that when activated, these microglia produced nitric oxide (NO) and tumor necrosis factor (TNF)-α. NO and TNF-α can be toxic to myelin-producing oliogodendrocyte cells. EAE and MS are diseases associated with the loss of myelin. These researchers demonstrated that by introducing E3, E2 or progesterone into cell cultures, the production of NO and TNF-α by the microglia was inhibited. The dosage of these hormones mimicked the levels produced during pregnancy. These results suggested that E3 inhibits microglia cell activation which may result in a decrease the severity of multiple sclerosis symptoms.

I'm really excited about how all this ties together!

 

[Hip]

Very interesting about the possible microglial activation inhibition effect of estriol. I already get considerable anti-anxiety benefits from N-acetyl-glucosamine and turmeric, which are both thought to inhibit microglial activation. † †

Regarding estriol's half-life: I also saw figures of around 1 hour. But I read on one estriol cream website that you only need apply the cream once every two days, because it has long lasting effects. Possibly the skin or mucous membranes act as a slow release mechanism.

I can also confirm that with my own transdermal tests of estriol, its effects seemed to last for a good 24 hours or more — much longer that its plasma half life of 1 hour would suggest.


Note that your 2 mg estriol dose would be equivalent to around 40 mg of estriol taken orally. (As mentioned above, a study found that 0.5 mg of estriol applied intravaginally is equivalent to 8 to 12 mg of estriol given orally).

So you appear to be taking amounts quite a bit higher than the 8 mg oral dose used in the study you quoted.

I agree it is exciting!

 

[Ema]

Note that your 2 mg estriol dose would be equivalent to around 40 mg of estriol taken orally. (As mentioned above, a study found that 0.5 mg of estriol applied intravaginally is equivalent to 8 to 12 mg of estriol given orally).

Hmmm, that's true and I missed that the first time. Thanks for pointing it out again! I'll have some trouble lowering the dose this month as it is mixed up with my progesterone but once I get the single cream, I'll be able to use the micro-spoons to dose. I wish that the oral forms didn't have the risky metabolite as it would be far easier to use.

I've been feeling better (knock wood) in the past week or so after my crash last fall. I wonder if it is my microglial tamping down to lower glutamate plus removing as much glutamate as possible supplements plan...or just coincidence? Either way, I'll take it.

 

[dangermouse]

@Hip did you try the estriol again? What did you think? I'm considering asking my GP about HRT for my peri menopause symptoms and wonder if estriol would be a good option re: ME too.

 

[Hip]

@Hip did you try the estriol again? What did you think?

Only occasionally, for one ot two days, as I would not want to take it long term due to the feminizing effects.

 

[dangermouse]

Only occasionally, for one ot two days, as I would not want to take it long term due to the feminizing effects.

Ah, yes, I can understand that. I'm thinking about it, it's a difficult decision though.