Estriol

Tell us what you are using to treat your MS-- and how you are doing.

Estriol

Postby goofygirl » Thu Oct 11, 2007 2:23 pm

Does anyone else use Estriol to treat their MS?
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Estriol and Progesterone for MS

Postby Shayk » Wed Oct 17, 2007 7:07 pm

Hi goofygirl

The answer is yes. I’m 61 (diagnosed RRMS at 57) and have been taking 8 mg of estriol for about 3 years. It’s part of what I do to try and help manage the MS. I’m also on 500 mg of progesterone (had none of that when I had my hormone levels tested), try to eat a low saturated fat diet, exercise, take supplements and am on Copaxone. I’d say so far so good.

I’m curious, have you considered having your hormone levels tested to determine if you have sufficient progesterone? I’m always bugging people to at least think about it since there’s some info that the ratio of estrogen to progesterone might be a factor in MS.

The ratio of estrogen to progesterone was linked to the number of lesions in two small studies.

Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis

MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns

And, since hormones exhibit several neuroprotective properties in animal studies and there’s been some research linking disability levels with age, I also personally wonder if the decline in hormone levels as we age might be a factor in the transition from RRMS to SPMS.

Low BDNF levels specifically have been linked to progression in people with MS and low hormone levels (progesterone and estrogen) have been linked to low BDNF levels.

Brain-derived neurotrophic factor in patients with multiple sclerosis
Significantly lower BDNF values were found in unstimulated and stimulated PBMC supernatants of patients with SP MS compared to control subjects. This reduction was greater in patients with a 1-point increase in the EDSS score in the last 6 months compared with that in patients without a progression of the disability score. Reduction in the levels of BDNF was also confirmed in the CSF of SP MS patients compared with R-R MS patients assessed during a stable phase of the disease and control subjects.

Now, the link to low BDNF levels and hormones (low hormone levels associated with low levels of BDNF).

Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor
BDNF was positively correlated with E(2) and progesterone and negatively correlated with menopausal age.

I think progesterone levels start to decline before estrogen so it’s some food for thought if you haven’t considered it before. I nearly forgot progesterone might also help with remyelination.

Progesterone: Therapeutic opportunities for neuroprotection and myelin repair

Hope you'll let us know periodically how you’re doing. I’m optimistic about the potential of hormones to help manage MS. And the mouse research for progesterone has started. 8)

Take care

Sharon
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Postby goofygirl » Thu Oct 18, 2007 5:17 am

Sharon, Thank you for your reply. I had given up that anyone else was using Estriol.
:)
I am curious why you started using it. I found the small study done at UCLA during a very late/early morning search about 4 years ago. It made sense to me for my situation and I felt very strongly it was what I should do. I was diagnosed 4.5 years ago with r/r ms and used Rebif for about 3 months but felt with every shot..it was the wrong thing for me to do. I order mine from a website and it is delivered from the uk. I don't like compounding pharm.

I had not read about the possible progesterone link. I will read about that. Off the top of my head my concern about the progesterone addition is ... there are so many issues associated with progesterone. More so when combined with estrogen. I had to have a complete hysterectomy when I was 24 (now 44) so I have had some experience with hormones. The worry of blood clots, reduced bone (osteoporosis sp?) increased risk of breast and uterine cancer... and others. I don't have to worry about the uterine cancer but others do. I haven't read up on all of this for some time so forgive me if I don't have it all. Again, my situation with the hysterectomy makes my situation a little different.

Thank you for the information, I love to look things up so I will definately look into it. I too am very excited about the 3rd trial with the estriol/copaxone trial. I don't use the copaxone. I just take 8mg a day... so far only 2 true replases in 4 years and still going!

Bless you and please keep in touch!
Lisa :lol:
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Postby Shayk » Thu Oct 18, 2007 6:32 pm

Hi Lisa

Funny you should ask how I heard about estriol.

Actually the very first piece of advice I got after learning I had MS (about 20 minutes after I got the news) was to take estriol. I’d never heard of it. I checked it out and decided it was a “must have”.

In my case I connected the MS diagnosis with having been whipped off HRT when the WHI info was released. I know that could be totally coincidental. It took me slightly over a year to actually get a prescription for it and that was conditional on being on a standard treatment. I had one relapse about 3 months after starting Avonex (which I was on for about 3 years) before switching to Copaxone. I haven’t had any more relapses and none since I’ve been on estriol/progesterone.

Your concerns about the risks of hormones are more than understandable given your history and I definitely think everyone needs to consider them individually. As I understand it, the basic info at this point in time seems to be that HRT may not be as “risky” as previously portrayed, synthetic “progestins” may be particularly problematic, and starting HRT at an early age may actually have some benefits.

Here are links to full text articles (pdf) that I’ve found helpful. The first article is on “synthetic” hormones and the second one on bioidentical hormones.

HRT: a reappraisal of the risks and benefits

A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks

I know “bioidentical” hormones and compounding are quite controversial. I’m using the compounding pharmacy that someone in the UCLA trial used and that was also recommended by the Chair of Ob/Gyn at a medical school so I have some degree of “confidence” in it.

A synthetic version of progesterone is in a clinical trial for post partum relapses but I think it will be some time before the outcomes are known. I contacted them recently and they’re not anticipating full enrollment until sometime next summer.

Best of luck with your own research into all of this. I think it’s something everyone should do.

Take care

Sharon
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estriol

Postby dg980 » Mon May 12, 2008 10:28 am

Hi Girls-

I have been using 4mg. of estrol for about 8 mos. and I now have cistic acne. Is this the cause? No progesterone being used. Should a go up to a dosage of 8mg.? Why do you not lke the compound pharm?
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Hormones/Acne

Postby Shayk » Mon May 12, 2008 7:14 pm

Hi dg980

I really don't know jack about acne. I've been on 8 mg of estriol and 500 mg of progesterone for several years now and acne hasn't been a problem. I've not read about acne being a side effect of estriol, but then not a lot of research has been done on it (in the U.S.)

Having said that, I do know that stress and fluctuating hormone levels can contribute to acne (adolescence, perimenopause), as can high levels of androgens (testosterone/DHEA). So, I'd think it might be wise to have the acne checked out by a dermatologist and to also have your hormone levels checked.

I'd definitely also think you might want to consider adding progesterone (especially if you have a uterus). If you have your hormone levels checked they would be able to advise you about that and on the dose to prescribe. Initially I didn't have any progesterone.

Re: compounding pharmacies--they come under criticism because they are not monitored by the FDA--so some people question "quality control". And of course, big pharmas really don't like them.

Re: 8 mg of estriol--that's the dose that was used in the pilot trial, which I think was based on estriol levels in about the 8th month of pregnancy. I think it's really up to you/your physician if you want to go from 4 to 8 mg. Unfortunately there's just not a lot of data to go on at this point.

Copaxone--I quickly checked the side effects and it seems 2% of people on it reported acne as did 2% of people on placebo...so, probably not the Copaxone.

Sorry not too much info here. Here's hoping the estriol is helping to manage the MS, despite the acne, and that someone more knowledgeable comments.

Take care

Sharon
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Postby DIM » Mon May 12, 2008 11:14 pm

As DHEA is precursor of Estriol, Estradiol, progesterone etc isn't better to take DHEA supplements so your body can produce the required amounts of each one of the rest and not estrion and progesterone?
I have read this way the body balances better it's hormones.
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Postby dg980 » Tue May 13, 2008 5:11 pm

Thanks Sharon, that was so sweet of you to do research for me. I did go to a Derm and she has me on 90mg of Solodyn (extended release minocycline). Some improvement but not cured. I noticed symptoms began to take place, like pain in my muscles once I started the mino. The nero put me on baclofen. As for you DIM.....what was that you just said? I did not understand a word. Maybe I am truly losing it.
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Acne/Hormones

Postby Shayk » Wed May 14, 2008 7:41 pm

DIM

We might be looking at different sources re: the pathways for hormones.

I have no medical or scientific background, (so definitely can't say this is necessarily correct) but one diagram I use as a reference does indeed indicate (quite consistent with what I've read), that DHEA is a precursor to estriol in one pathway and to testosterone and then estradiol in another, but is not a precursor to progesterone.

One pathway is cholesterol, pregnenolone and then progesterone.

Another pathway is cholesterol, pregnenolone and then DHEA. The DHEA converts into estriol and testosterone (initially via two different pathways) and the testosterone converts into estradiol. (Taking some short cuts here).

So, you're right, it seems that if one's DHEA levels are low (and that's pretty consistent in people with MS in the few studies that reported it), taking DHEA is one way to potentially increase and "balance" estriol, estradiol and testosterone--but not necessarily progesterone ??

My DHEA was actually low, but the physician recommended progesterone as the "balancer" and to increase my DHEA level and if that didn't work, we'd add DHEA.

A little OT, but in the study that found disability levels in men associated with low levels of estradiol, one idea of the researchers was that perhaps men with MS have a problem converting testosterone to estradiol.

dg980

I think what we're talking about is how hormones are converted and/or transformed into one another and which ones come first before being converted to something else. Amazingly, they all start with cholesterol.

I don't think I'd necessarily start with DHEA though in your situation until you find out if your level is low. Per this abstract

Assessment of androgens in women with adult-onset acne
CONCLUSION: DHEA-S plays a key role in the pathogenesis of adult-onset acne. Measurement of circulating androgens, including DHEA-S, especially in patients presenting with adult-onset acne and hirsutism, is helpful, and patients with elevated levels can benefit from hormonal therapy.

I'm surprised your dermatologist didn't seem to indicate what the "cause" of your acne might be. It's interesting about the mino. I think they originally identified mino as a possible MS treatment from observing that people who were taking mino for acne were doing quite well re: their MS. Personally I think mino has great possibilities as a neuroprotective agent and in the management of MS. Sorry you've had muscle pain with it. It is in clinical trials for MS too--just in case you didn't know.

Best of luck in resolving everything and welcome to the site.

Sharon
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Postby DIM » Wed May 14, 2008 10:58 pm

Thanks Sharon for explain all these thinks for me.
Actually you are right, DHEA isn't a precursor to progesterone but progesterone as reffered to some trials doesn't help in MS contrary to estriol-estradiol (estrogen that the body produces from DHEA) that stop MS progression in some cases!
On the other hand progesterone probably in synthetic form may cause cancer while DHEA hasn't such effects, I wonder why your physician recommended progesterone, is there any problem with the DHEA supplementation at all?
Here is a guide about hormones mainly for fertility:
http://www.fertilityplus.org/faq/hormonelevels.html
Dim
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estriol

Postby dg980 » Thu May 15, 2008 6:01 am

Well, I really have the info to figure this out now. About the mino, I would highly recommend to everyone that wants to do this treatment to demand Solodyn, not the generic. This is very expensive, $500 for a 2week supply. But the good news is the company will give you a prescription card and it should cost you little or nothing. With my insurance it cost me 0. And once you run out of benefit under their card, they will give you another one. I can definitely tell a difference because when I did the twice a day mino, there was no difference at all. This may be an answer to better ms management as well as acne management. My dermo said that alot of women that hit their 30's have acne in the hormonal areas. I was flattered because I just turned 40! As for the estriol, has anyone tried a cream? I noticed you can get this on the internet.
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DHEA/Estriol/Progesterone

Postby Shayk » Thu May 15, 2008 7:09 pm

DIM
progesterone as reffered to some trials doesn't help in MS contrary to estriol-estradiol (estrogen that the body produces from DHEA) that stop MS progression in some cases!

I'm not aware of any progesterone trials that didn't help MS so please share more.

I am aware of an EAE trial with progesterone only that was damaging, but it was not damaging if administered with estrogen and I think I recall that the progesterone dose may have been supra-physiological. With the hormones I've read about, it seems like all of them have the potential to be damaging to people with MS if the levels are too high or too low (even DHEA--although I can't recall the specifics of that at the moment :( )
On the other hand progesterone probably in synthetic form may cause cancer while DHEA hasn't such effects, I wonder why your physician recommended progesterone, is there any problem with the DHEA supplementation at all?

Agree with you about synthetic progesterone and cancer. I'm all for bio-identical hormones. I don't know that there's really been a lot of research about DHEA and cancer. There are cautions for men and high DHEA/prostrate cancer simply because it's an unknown.

Other concerns about DHEA are that because it does convert to testosterone/estradiol, people need to have their levels checked periodically to be certain those hormone levels stay in the "normal" zone--at least I would. In one study high and low levels of testosterone were associated with MRI lesions in women and a similar impact was seen re: estradiol levels in men.

Sex hormones modulate brain damage in multiple sclerosis: MRI evidence

Another concern about DHEA re: converting specifically to estriol, is that I wonder how much DHEA it would take to increase one's level to that roughly equating the third trimester of pregnancy (if that's the goal) Is it possible?

I think my physician recommended progesterone as the "balancer" because of the feedback loops among hormones and to oppose the estriol to help prevent uterine cancer. I appreciate the link.

Here are some articles that may or may not be of interest--the first is about DHEA and progesterone.
Endogenous neuroprotective factors: neurosteroids

About DHEA only--has good references though re: DHEA/MS research and is available through Sage Publications through May.
Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone

Abstract only--Does progesterone have neuroprotective properties?

Progesterone and TBI Trial--at least some of progesterone's neuroprotective properties seem to be operational in people. :) Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial

dg980

Sounds like you're well on your way here. Nice tip about the mino. I haven't tried estriol cream--personally I'd only go that route if the manufacturer has independent lab testing verifying their product. My compounded estriol is less than $30/mo.

Sharon
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Postby dignan » Thu May 15, 2008 9:25 pm

Slightly OT, but Sharon I just wanted to express my awe at how much you know about hormones and MS. I'm pretty sure there are few neurologists who are as well-informed as you.
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Postby DIM » Fri May 16, 2008 1:00 am

Sarah while searching how gonadotropin affects MS I found two studies that say there is no neneficial effect from progesterone at all, if you want I'll find them again.
But as you already said most imprtant is to have all hormones balanced rather supplement them!
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Postby DIM » Fri May 16, 2008 2:20 am

Sarah:

Hormone Imbalances and MS
In recent years, researchers have made great progress understanding how hormone status affects autoimmune disorders, including MS. Numerous studies have observed that MS is more common in women, and that the disease course is affected by the normal ebb and flow of steroid hormones during a woman's monthly menstrual cycle (Pozzilli C et al 1999). Interestingly, it is also well known that pregnancy tends to neutralize the disease course, or even positively affect it, enabling women who have MS to bear children safely (Hughes MD 2004).

These findings point to the important role of steroid hormones in influencing the course of the disease. This theory makes even more sense considering that sex steroid hormones such as estrogen, testosterone, progesterone, and dehydroepiandrosterone (DHEA) are known to have immunomodulatory effects. Hoping to better understand the role of hormones in MS, a number of researchers have conducted studies. Their findings include:

-In a study on rats, researchers found that animals given progesterone alone experienced greater motor defects and inflammation than rats treated with estrogen. The negative effects of progesterone were negated when estrogen was added (Hoffman GE et al 2001).

-Administering estrogen (including estriol and beta-estriol) along with progesterone was shown to inhibit production of nitric oxide in central nervous system cells. This effect was enhanced when the levels of estrogen and progesterone were maintained at levels found during late pregnancy (Drew PD et al 2000).

-Estriol treatment significantly reduced disease severity in animals with MS, while treatment with progesterone had no effect. Administering estriol until treatment levels reached levels consistent with those in late pregnancy completely ameliorated the disease (Kim S et al 1999).

-During a human study that examined the presence of MS lesions by magnetic resonance imaging (MRI), patients with high estradiol and low progesterone levels had more lesions that those who had low levels of both hormones, while patients with a high estrogen to progesterone ratio had a significantly greater number of active lesions than patients who had a low ratio (Bansil S et al 1999).

Obviously, these studies point to a conflict in our understanding of the role hormones play in MS. Animal studies have tended to show progesterone as neutral, while estrogen seems to have a protective effect. In people, however, a high ratio of estrogen to progesterone was associated with more MS lesions. Accordingly, there is a great deal of debate among researchers about the possible role of hormones in MS therapy. Some studies (aimed at maintaining levels of estrogen to progesterone that are consistent with late pregnancy) have argued in favor of treating women with MS with bioidentical hormone replacement therapy. Other studies note that pregnant women who have MS tend to experience a rebound of their disease the first 3 months after delivery (El-Etr M et al 2005). According to a recent review, more studies are needed to determine the exact relationship between MS and hormonal imbalances (Trenova AG et al 2004).

DHEA also deserves attention in people of both sexes who have MS. DHEA is a steroid hormone. Altered levels of DHEA have been associated with various autoimmune diseases and their symptoms, including MS (Calabrese VP et al 1990). One study found that people with MS have relatively lower DHEA levels compared to healthy control subjects and that, at least in animals, DHEA therapy reduces T-cell proliferation, secretion of pro-inflammatory chemicals, and nitric oxide synthesis (Du C et al 2001; Offner H et al 2002; Ramsaransing GS et al 2005). Similarly, researchers have found that people with MS have a higher ratio of cortisol (the body's main stress hormone) to DHEA than do healthy control subjects, although this is probably a symptom of the disease rather than a causal factor (Kumpfel T et al 1999).
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