This Is MS Multiple Sclerosis Community: Knowledge & Support

The following information on Estriol treament was generously contributed by Shayk. It is through the active participation of our members that we bring value to the community, so please send Shayk some warm thoughts. This information has been added to the Encyclopedia entry on Estriol (look here: http://www.thisisms.com/encyclopedia-5.html), which is shaping up as a promising possible therapy for MS:

Subramanian, S, et al,
"Oral Feeding with Ethinyl Estradiol Suppresses and Treats Experimental Autoimmune Encephalomyelitis in SJL Mice and Inhibits the Recruitment of Inflammatory Cells into the Central Nervous System,

Journal of Immunologoy, 2003, Feb. 1; 170(3)1548-55.
The last line of the abstract concludes: These results suggest that oral ethinyl estradiol might be a successful candidate as therapy for multiple sclerosis.

Another article by Foster, SC, et al, Dysregulation of the hypothalamic-pituitary-gonadal axis in experimental autoimmune encephalomyelitis and multiple sclerosis.

Journal of Neuorimmunology, 2003 Jul; 140(1-2):78-87.

The last line of this abstract states: Gender differences in the sensitivity of the hypothalamic-pituitary-gonadal (HPG) axis to inflammation may be an important factor regulating the duration and severity of central nervous system (CNS) auoimmunity.

The last is by Liu, HB, et al, Estrogen receptor alpha mediates estrogen's immune protection in autoimmune disease.

Journal of Immunology, 2003 Dec 15; 171 (12): 6936-40.

(This is part of Voskuhls work at UCLA and the last line of the abstract states: These findings are central to the design of selective ER modifiers which aim to target biologic responses in specific organ systems.

Shayk.......Thanks for the great article. I was DX very shortly after going off HRT remember.......This sounds like a potential++.

Thanks again.......Kim

Kim

You're giving me a great excuse to get on my soap box about hormones and MS

Lucky you and everyone else though, this relapse has me too tired and too much in the MS brain fog to do a decent response or summary.

I'm still hot into researching the topic tho and will post more food for thought later.

A tidbit for everyone, yes, there is research on testosterone and MS too.


Sharon

ok, just a few things since I can't seem to get it all organized for a decent posting.

First, www.nationalmssociety.org/Soucebook-Hormones.asp gives a nice overview.

Quoting that source, "Both testosterone and estriol, an estrogen hormone that is produced during late pregnancy have been shown to have a beneficial effect in EAE (animal model of MS)."

Voskuhl's small estriol pilot showed + findings for women with RRMS. It's my understanding they're now doing a pilot of testosterone gel with men.

Now, the laugh is on me. "How brilliant is that?" No one's interested in this estriol HRT since I must be the oldest one here.

Never mind , younger women may want to check out
www.mscare.org/professional.ofn?doc_id=200 for an article entitled
"Understanding Fluctuations of Multiple Sclerosis Across the Mentstrual Cycle", by Houtchens, et al.

If nothing else, it contains a great chart for recording your cycle and associated MS symptoms. You could give it a shot to see if there's any association for you personally between the two.

For women so inclined and whose health allows the use of birth control, some bc formulations contain ethinyl estradiol. (Effective in the mouse study.)

Lastly, old news, but I just found it. The FDA gave investigational drug orphan status to bring VG1000 to market. It's been developed by OHSU/VA scientists and I'm guessing it contains some SERM since Offner mentioned it the interview on estrogens posted here. Info about the orphan drug is at www.ohsu.edu/news/2003/051303fda.html

Cheers to all and to all a as we continue to battle MS

Sharon

Here's a news flash for the guys! Voshkul has an article coming out in the Journal of Neuroimmunology on estriol in male EAE mice....

Estriol treatment ameliorates disease in males with experimental autoimmune encephalomyelitis: implications for multiple sclerosis

Karen M. Palaszynski , Hongbiao Liu , Kyi Kyi Loo and Rhonda R. Voskuhl ,

Department of Neurology, Reed Neurological Research Center, University of California School of Medicine, 750 Westwood Plaza, Los Angeles, CA 90095, USA


Abstract
Estrogen treatment has been found to be protective in experimental autoimmune encephalomyelitis (EAE) and possibly multiple sclerosis (MS). We investigated whether the effect of estrogen treatment is gender-specific. Estrogen receptor (ER) expressions, ER and ER, were found to be equivalent in both genders. EAE disease severity in both females and males was decreased with estriol treatment as compared to placebo. Finally, proinflammatory cytokine production during autoantigen-specific immune responses was decreased with estriol treatment in both females and males. These data support a potential role for estriol treatment for men in addition to women with MS.

You know what's really ironic (to me personally at least)

My "hormone" profiles indicated I was low in testosterone, so they've put me on that. (Not for MS tho) So guys, now you get estriol (a form of estrogen).

Go figure...this is MS!

Sharon

Yeah, a study in California a few years back said that estriol does help MS in humans, at least the RR form of MS. Catch is, estriol is harder than heck to get in the US - a prescription and a compounding pharmacy are both needed, and the former means you'll need a well-informed neuro (or possibly a sympathetic endoc).

Estriol is not your normal "estrogen" - that's estradiol. Estriol is formed by the placenta of pregnant women, and it's an immunomoderator; it "tells" the immune system to go easy on "invaders", to protect the developing fetus. That also protects against MS, which is why many pregnant women see a temporary remission while they're pregnant.

I was on it for about a year, but my neuro had not clue #1 about the correct dose. After a year, it hadn't done me any good, so I stopped. YMMV.

If you want, I can probably find the pharmacy again. They do mail-orders, with a valid prescription.

Thanks for this info and your experience with it.

I am really to hear that it didn't work for you. I have been so hoping that it would positively complement the Avonex. Rats!

Your experience is identical to mine, 2 neuros and 3 ob gyns later I've gotten my primary care doc to agree to hormone replacement therapy via a compounding pharmacy.

Still not at the dose used in the trial at UCLA tho.

Curious, did you test and monitor all hormones, or just tried the estriol for a year with no results?

Sharon

I've been on HRT for a while anyways, so my estradiol level depends on how well I remember to take my pill. My testosterone level is nearly zilch (libido? What's that?), and other than the estriol that's all I've checked (progeserone is about zilch, too. No hot flashes, thankfully)..

Estriol might help you with Avonex. I think I was a day late and a dollar short, by the time I finally browbeat my neuro into prescribing it. A while back, I read how the study went, and that it helped MS at the RR stage, but not at the SP stage, and I'd been at that stage for years before I ever heard of estriol.

Well, I am really sorry the estriol didn't work for you and that you're "past" RRMS.

I am though that maybe there's a chance it will help me with the Avonex since I think I'm still RRMS. I've been diagnosed less than a year and am coming out of a relapse. (I hope) Time does seem to be of the essence.

I am originally from Oregon, and I can assure you that in Virginia medicine is much more conservative than on the west coast. There's a MS neurologist in Virginia who is actually doing research on post menopausal women with MS re: the impact of HRT on cognitive functioning. She politely told me she doesn't prescribe the estriol.

The chair of ob/gyn dept. at one of our medical schools also said I'd never find anyone in Virgina to prescribe it, so I'm "back dooring" it, have pharmacist tell doc. Hope it works.

I think I'm on the way. Transferred low dose hrt biest script just today to pharmacy in Wisconsin.

For some reason I can't read your "introduction" to this site. Comes up blank, but welcome, glad you're here!

Sharon

Yeah, let's hear it for "conservative" doctors who are unwilling to learn anything new about an incurable, progressively-debilitating illness. Blargh!

Glad to hear that you found estriol anyways. I've oft wondered is Premarin might work nearly as well - it's made from pregnant mare urine, so it's going to be mostly estrone and estriol. Problem is, I may be crazy, but the idea of swallowing horse p*ss, and *paying* for it, doesn't really thrill me.

As for my intro, hmm ... I'm 44 years old, had my first major attack in 1994, and have gotten steadily worse since then, with a bunch more attacks, too. I was dx'd late 1997, and was told not to worry about it - why, odds were that I'd never even need a wheelchair! By 2002, after I'd wheedled my neuro into referring me, the OT took one look at me and said that I'd needed the electric wheelchair for years.

I'm still sort of ambulatory - if everything is perfect, I can slowly hobble five, maybe eight feet before I fall. Otherwise, I cruise around in my nifty Jazzy 1113 chair named "Elspeth." I used to work as a software engineer, but now I'm on disability. I try to avoid stress as much as possible these days, mainly by sleeping a lot, petting my 4 cats, and cutting gems to make into jewelry.

Oh, and I live in Seattle.

Hope you can see this

Ms. Willow

Thanks for the intro info again. I was eventually able to see it in the other thread. Embarrassing for this technologically challenged person to be messaging a software engineer but oh well

I’m still pursuing “the best possible management of MS for myself” and that includes info on estriol and trying to figure out if I should keep trying to get to the 8mg dose. Since you’re in Seattle, do you know anything about the reputation of the Tahoma Clinic in Renton? Is it highly regarded? Or, otherwise?

That internet site was one of my “earliest” sources of info on the 3 types of estrogen: estrone, estradiol and estriol, and, so far the only site I’ve come across where there was a recommendation for women with MS to possibly consider estriol (in light of Voskuhl’s research) if more conventional MS treatments were failing.

As I understand it, since estriol is not considered a drug per se, (since it’s a naturally occurring hormone), there have not been many studies about its safety or the side effects. (In US anyway, FDA approval for estriol is not required, but you still need a prescription to get it compounded. And, coincidentally, that could be why the drug companies aren’t studying it for MS either. There’s no money to be had, sort of like LDN. I think NMSS funded Voskuhl’s research.)

However, the little bit of info I’ve been able to find actually suggests that it protects against breast cancer (Tahoma Clinic info and one study I found) and is frequently used for HRT in Europe and SE Asia. I even read one study where they start at 8mg for HRT (dose used at UCLA trial for women with RRMS) and then taper down to determine lowest “effective” dose for menopausal symptoms. Did you by chance learn anything about the safety and risks of estriol when you tried it?

I've decided to steer clear of the horse's urine type of estrogen!

Thanks so much! (I will be out of the country for about 10 days but will definitely check to see what you have to say about this.)

Lots on estriol today!

BTW, for anyone who may be following this thread but not commenting, while the WHI study provided women with very important information about the risks of HRT (using conjugated estrogens and progesterone, specifically Prempro), I strongly advocate that women do their best to personally understand their own risk(s)/benefit(s) when it comes to considering hormone therapy of any type for any reason.

My personal risk calculation using the WHI info on Prempro for HRT, (I used a Univ. of VA newsletter on this topic) and absent a family history of breast cancer, is that over the course of 5 years, I have a 1% (1 in 100) risk of developing one of the increased risks associated with Prempro HRT, that is, breast cancer, heart attack, stroke, or blood clots. The reduced risks were hip fractures and colon cancer.

There are HRT options besides Prempro! (My estriol is compounded from soy and the progesterone from yams.)

It’s my personal opinion the media’s presentation of the WHI data as a 28% increase, yada, yada, yada, while accurate, has done very little to inform women (and, regretfully, many ob/gyns) of what the risks actually are. For me, the questions are: What are my risks for these conditions without HRT? What are my risks with HRT? What are the benefits of HRT? And, hey, since I have MS, there may be another benefit.


All things considered, I was willing to take a 1% risk over 5 years (best available information on HRT) to try to decrease the number of potentially disabling brain lesions (100% risk) I’m almost certain to have from the MS. I'm using estriol/estradiol based HRT.

As people say, read, read, read.

And, sorry guys, but it does seem there is some info hormones may be good for you too!

Sharon

Hi again!

Trying to keep all of this on the estriol thread.

Found some related info on the estrogen receptor alpha. This is the receptor that Voskuhl reported was protective in the mice EAE. And remember, Voskuhl did the small pilot with estriol that showed promise with women with RRMS.

Anyway, trying to be ever hopeful better therapies are on the horizon, I found this article by Dubal, et al, Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury. (Proceedings of the National Academy of Science, February 13, 2001, vol. 98, no. 4, pages 1952-1957)

The first line of the abstract from this article states: “Estradiol protects against brain injury, neurodegeneration, and cognitive decline. The last line states: “Our discovery that ER alpha mediates protection of the brain carries far reaching implications for the selective targeting of ERs in the treatment and prevention of neural dysfunction associated with normal aging or brain injury.” (Their mice didn’t have EAE tho). Remember too that Offner, from OHSU, seems to be working on a SERM (selective estrogen receptor modulator) as a MS therapy.

To the extent that I understand some of the issues with MS (and my understanding is minimal I assure you), a couple of other lines from this article that struck me were:

“ER alpha is critical in all brain regions protected by estradiol…..ER alpha plays a crucial role in neuroprotection via mechanisms that are likely independent of blood flow.”

That’s the update for now.

Take care.

Sharon

Thanks for the good info Sharon.......Kim

Catching up, after having been a busy grrl cutting rocks this past week. Far as I know, the fact that estriol is naturally-made does not mean that it's not under FDA and drug company's ability to control ... but, as a naturally-occuring hormone, they can't get a patent on it, so there's not a lot of money to be made here. The estradiol that I take is 17beta-estradiol, which is, I think (and have been told) the same form as made in the body. Seemed much safer than the synthetics, or the horse pee too.

I haven't heard about the Tahoma clinic, unless it's the one that had been associated with the guy who concocted Procarin several decades ago. If it is that one, then I'd steer very clear of them. Procarin is great, for making one woman wealthy, but histamines, whivh are part of an inflammation attack, are decidedly NOT good for MS. Caffeine will, indeed, alleiviate fatigue, but as the body gets used to it, an increasingly=higher dose is needed... and besides that, NoDoz pills are far less expensive than the Procarin patch. So, if this clinic was connected with Procarin, well ... Draw your own conclusions.

Updates on Alpha Lipoic Acid - today was the absolute end of my taper-down oral steroid dose. It's been nearly 2 weeks since my IV steroids, and I've been taking ALA, 1200mg/day the whole time. No sign of gingivitis at all, which means the inflammation has gone away systemicly. Yay! Hopefully, this will translate into no more MS attacks.

And with that, I'm off to nap a bit, then get my next rock creation going. This will be a yin-yang pendant, in red and green aventurine set in syerling silver. I've got two nicely-matched color and sparkle slices of stone, and just need to lay out the pattern on the slabs, then jig-saw them at the next workshop. This is gonna be fun! Wheee, time to enjoy life again