My wife has RRMS cannot take interferons (persistent elevated liver enzymes) or Copaxone (allergic reaction after 2 months) anymore. Her neurologist, who is great, is recommending pulse steroids every 3 months.
We have agreed to this, and she is due to start another round in a few weeks, however reading up about the new estriol trial is making us wonder whether 8mg of estriol per day would be better.
Regular pulse steroids have shown some interesting results in small trials, but there is also evidence of them becoming ineffective eventually. I am, however, pleased that regular pulse steroids have shown good effects on atrophy (which is very important).
On the other hand, estriol is a little more of an unknown quantity with MS. A few issues:
- we don't know if the neurologist would even agree to prescribe estriol; and
- my wife is under 30, so concerned about using a hormone replacement drug at a young age.
If we were persuaded that estriol is the way to go, we could probably find a way to get a prescription, even if the neurologist said no. We have very good friends who are GPs.
At the moment, my wife is otherwise observing a low saturated fat diet (Swank/Jelinek style), and supplanting with high potency omega-3 fish oils (Nordic Naturals brand). She is doing quite well (touch wood), although at the moment she is feeling the remnants of a relapse of 3 months ago (she was given steroids for this).
If we go the steroids, we anticipate doing this for about a year, and then trying for kids (which would be another way of getting estriol!). Interestingly, the neurologist said that if Tysabri were available (it's been approved in Australia, but not approved for government subsidy yet - probably a year away) he would give it to her straight away. This really worries us (PML, monoclonal antibodies in general) so the fact that Tysabri isn't available yet is actually a good thing (we think).
Sorry for the rant, thanks in advance!
There is a recognized connection between MS and Type 1 Diabetes. If your wife tries steroids, this is just one more thing to talk to her doctor about, watch for, and maybe test for.
By the way, researchers in Scotland (Behan and Chaudhuri) stated in a paper (posted by finn under General Discussion) that pregnancy was more effective than the interferons.
I have no doubt. The neurologist was completely unsubtle in telling us to start reproducing asap. Life ain't that simple though... once you have kids, life is never quite the same is it...lyndacarol wrote:By the way, researchers in Scotland (Behan and Chaudhuri) stated in a paper (posted by finn under General Discussion) that pregnancy was more effective than the interferons.
Personally I'm very biased for estriol.
If your wife's concern is fear about the risk of breast cancer and estrogen, based on research with menopausal women in the US, surprisingly (even to me) that concern appears to be unfounded.my wife is under 30, so concerned about using a hormone replacement drug at a young age.
From this link
Of course, this research was not with estriol specifically and clearly it was in older women. Unfortunately I don't think there's long term data about estriol per se.Why was the estrogen-alone study stopped?
In March 2004 the estrogen-alone study was stopped after an average of 7.1 years of follow-up because of evidence of an increased risk of stroke (44 women taking estrogen had strokes versus 32 women taking placebo), with no benefit for coronary heart disease. The increased risk of stroke was similar to what was found in the estrogen-plus-progestin study when that trial was stopped in 2002. Surprisingly, there was no increase in risk of breast cancer in women receiving estrogen alone and the trend suggested a 27% reduction. At the time the study was discontinued, enough data had been obtained to assess the overall risks and benefits of the use of estrogen in this trial.
This decision making is never easy and I wish you and your wife the best.
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I would think long and hard about pulse steroids every three months for your wife. Everything that I have read and/or heard about steroids is they are OK for short term use to reduce the severity or length of an exacerbation. But they do nothing to alter the course of the disease and each time they are used, they become less effective the next time. Steroids also have several side effects and some comments are that long term use may contribute to MS speed of progression.My wife has RRMS cannot take interferons (persistent elevated liver enzymes) or Copaxone (allergic reaction after 2 months) anymore. Her neurologist, who is great, is recommending pulse steroids every 3 months.
I would certainly be sitting down with my wife and her neuro to discuss ALL the ramifications of using this treatment. Ensure that he/she explains both the pros and cons of such a treatment (including the use of estriol)so that the two of you can make an informed decision on your course of action.
My wife and I were faced with the same decision many years ago about starting a family. We sat down with her neuro at the time and he explained all sides of the equation for us. One point he did make was that after pregnancy, which usually masks MS symptoms, the chances of an exacerbation go up quite a bit. His next point was to ensure that if we decided to have a family anyway, there was some kind of plan in effect to care for the infant should my wife suffer an attack. I'm not trying to influence your decision one way or the other but just trying to ensure that you look at the big picture in all of this.
Whatever decision you make, the best of luck.
Thanks Harry - I hear you loud and clear. I do have concerns about steroids, but at the same time, the pulsing would 'only' be for a year. Then we'd try for kids (hopefully two in quick succession). By that stage, we'd be hoping that her MS hasn't progressed and that some really good drugs will have become available.
You're more than welcome. You asked:
Yes, I’ve been on 8mg of estriol and 500 mg of progesterone for approximately two years. As to whether or not it’s helping me, I’m one of those people who think the nature of the disease itself makes it impossible to say whether or not I think it’s helping so I won’t even hazard a guess. In addition to the hormones, I also try to observe a low saturated fat diet, take supplements and exercise. I was also on Avonex for about 3 years and switched to Copaxone about 5 months ago.Are you on estriol - has it helped you?
What I can say (fingers crossed) is that to the extent there is a prognosis for any given individual (which I know there isn’t) I seem to be doing “ok” for someone who had a relatively poor prognosis at diagnosis. I was older, 58; had lots of lesions—more than 9 greater than 2 cm.; and, my onset consisted primarily of cerebellar symptoms.
Since being on hormones I’ve been relapse free, my gait has improved and for the most part any progression seems to be indistinguishable from aging. I continue to work full time, manage a household and on occasion even have some fun. It's also possible I have so called "benign" MS. Coincidentally (who knows?), I was diagnosed after they took me off hormone replacement therapy when the results of the WHI study were released.
My vote for estriol, besides the trial data, is predicated in part on my personal belief that estrogens generally seem to display a number of pre-clinical neuroprotective properties that may be relevant to the MS disease process, at least as it is currently understood. The AAN abstracts are still under embargo but are available for reading. There’s a very interesting one by the researchers pursuing the phase II estriol trial. If you search for multiple sclerosis and neuroprotection I think you’ll find it.
Since you’re considering a family, as an FYI, there’s also a clinical trial in Europe utilizing synthetic progesterone and estrogen to manage post partum relapses.
Not sure if any of that really helps, but from my reading, and please know I have no scientific or medical background, I remain quite optimistic about the potential of hormones (and not just estriol) to help manage MS.
A bit more info you and your wife might want to consider if she decides to choose estriol rather than pulse steroids and that is to have her hormone levels tested and depending on the results, to consider “balancing” the estriol with progesterone as indicated by the test results.
There is very limited information to suggest that for some women with MS the ratio of progesterone to estrogen, rather than the absolute amounts of these hormones, may be a factor in MS.
Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis
MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patternsRESULTS: Patients with high estradiol and low progesterone levels had a significantly greater number of Gd enhancing lesions than those with low levels of both these hormones. Patients with a high estrogen to progesterone ratio had a significantly greater number of active MRI lesions than those with a low ratio. CONCLUSION: Estradiol and progesterone may influence disease activity in MS. If further studies confirm these results, it may be possible to develop therapy by altering levels of these hormones.
The premenstrual period and exacerbations in multiple sclerosisThe ratio of progesterone/17-beta-estradiol during the luteal phase was significantly associated with both number (r = 0.6, p = 0.03) and volume (r = 0.7, p = 0.009) of enhancing lesions, providing support for a role of these hormones as immunomodulatory factors in MS.
That’s a phase when there’s a fairly significant shift in estrogen/progesterone ratios.The aim of this study was to assess whether an association exists between the premenstrual period and exacerbations of multiple sclerosis (MS)…..in 45% all exacerbations had started during the premenstrual phase
Last but not least I personally think there’s also good pre-clinical evidence to suggest that progesterone itself may have some potential immune modulating, re-myelinating and neuroprotective properties to help manage MS.
I thought it would be remiss not to mention this research if you and your wife are still considering estriol. This particular research is one of the reasons I favor "balanced hormone levels".
Again, best wishes to you and your wife in making a difficult decision.
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Sex hormones are steroid hormones, they shares the basic structure (core formula) and source of origin (cholesterol) with other steroids.
Short description of estradiol behavior could be – responsible for aggressive growth (tissue components) with lack of differentiation (blocks thyroids) with inevitably following destruction after; progesterone – differentiation of growing tissue with following protection from destruction.
They act directly after passing the blood-brain barrier as all other steroids do.
Speaking about brain, the effect on neuroplasticity lies that estradiol “fires up’ neurons leading to new dendritic spines with higher density of glutamatergic receptors and increased synaptic activity among neurons, in simple words – rough, amorphous activation which creates a ‘base’ for brain structural changes. Progesterone is responsible for synaptogenesis - controls this ‘wild’ activation, shapes (organizes) it and performs these structural changes, bringing the tissue to higher level of differentiation and specialization, which itself serves as protection from destruction.
Eighty-two per cent of menopausal women reported an increase in severity of MS premenstrually. There are well known facts that majority of seizures in women falls to this period also, even Hashimoto encephalitis flares up as well. Why? There is no increase of autoimmunity during these few days, too short time for that, but they have one common feature - decrease of progesterone/estrogen ratio and surge of estrogen.
In women with multiple sclerosis, the rate of relapse declines during pregnancy, especially in the third trimester (during increase of progesterone/estrogen ratio), and increases during the first three months post partum before returning to the prepregnancy rate.
Lower level of estrogen (together with almost zero level of progesterone) in PM women mimics (in certain degree, of course) the effect of corticosteroids. But the negative effect of estrogens on neuroplasticity in this case is muted/neutralized by increased estrogen/testosterone ratio and final result is usually positive, most MS women stabilize in PM period.
But if we increase the level of estrogen in PM women artificially, we will get the same negative effect as from prolonged use of corticosteroids: increased degree of scarification (with following accelerated axonal loss) and decreased level of remyelination (which is still possible) in MS lesions.
Degree of deterioration in PM women with MS usually depends on how much of disability they have before entering this period. Of course, if the brain defect is large, the following deterioration will be continued by common neurodegeneration rules (not because of MS!) with slow and steady progressions over the years or decades. That’s why we see the ‘switch’ in MS form in PM women, which, in some way, is made up.
The spectrum of steroids action is very complex, each of them has at least 30 various effects, but when talking about HRT for MS (and use estrogen alone!), well, it seems not reasonable at all. Most current explanations and proposals for estrogen use for ‘neuroprotection’ on MS based on speculation with its effect on autoimmunity only, well, we have seen that play before – all proposed ‘autoimmunity’ treatments have failed.
Please, don’t get ‘hooked’ on ‘enhanced lesions’ number in studies, it has nothing to do with disability. Read carefully the papers about MRI findings in MS, they always state – there is no direct clinical correlation between enhanced lesions on MRI and clinical course (disability).
Increased feeling of “well-being” and reduced number of ‘enhanced lesions’ during estrogen HRT therapy could be achieved with low doses of corticosteroids as well, but in a long run both variants will lead to increased disability.
We don’t even talking here about estrogens’ extremely strong carcinogenic effect (they go after cells genome) and complications of other kind such as weight gain, cognitive function decline, hypertension, etc.
In menstrual MS women estrogen therapy could give some anti-inflammatory benefits, but loses will be much greater, so it is not worth it. Corticosteroids are efficient for treatment during MS relapses (but not for prevention or long term use!).
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Sharon, have you noticed any side effects such as weight gain, breakthrough bleeding or depression while on estriol?
http://www.selfgrowth.com/articles/lee1 ... s&ie=UTF-8
In my case estriol has not resulted in weight gain, breakthrough bleeding or depression, but remember I’m using a “balanced hormone” approach and I’m also on 500 mg of progesterone. (I had zero when I had my hormone levels tested). And, don’t forget, progesterone has lots of neuroprotective properties that might be relevant to MS.
To add to the article you posted, I recently discovered the following article (the link is to a pdf file) that I think is a good one and addresses some of your questions and concerns about estriol.
A Comprehensive Review of the Safety and Efficacy of Bioidentical Hormones for the Management of Menopause and Related Health Risks
For people who don’t want to read the entire article, here’s a link to the abstract.
Since I personally think having your hormone levels tested and seeking balanced levels of several hormones is important, here’s a link to the Women in Balance research page that contains a lot of information and resources. In case anyone wonders, I’m not affiliated with the organization. It’s simply a resource I encountered when I was trying to decide what to do.
Now, good luck with your decision. It's never easy and I’m not exactly certain what you fear about estriol. If the headlines this week (again) about the decline in breast cancer since women stopped taking HRT scared you, I’ve some data about that I can post if you think it would help.
Here's wishing you and everyone the best.
Quickly, I’ll address right now only the info on breast cancer. I think what’s driving the “repeated headlines” is that researchers are comparing the breast cancer rates when many more women were on HRT (2002) to subsequent years (2003 and 2004) when many women stopped HRT when data was reported from the Women’s Health Initiative study.
Some questions I ask:
1. How significant was the decline in the risk of breast cancer between 2002 and 2004?
2. Is the decline in risk attributable to estrogen?
First, “The Risk”
Because I think every woman should decide the significance of these declines here are some actual numbers I’ve been able to locate about last weeks news. (Abstracted from an AP News article)
In 2002, there were 135 cases of breast cancer per 100,000 women reported.
In 2003, there were only 126 cases of breast cancer per 100,000 women. As they say and everyone reports, “That is the most significant decline in the breast cancer rate since records have been kept beginning in the 1970s.” (December 2006 news)
In 2004, again there were 126 cases of breast cancer per 100,000 women. (April 2007 news)
Here’s another way to look at the data. (I translated it into something that helps me better understand the risks/benefits.)
Breast Cancer Incidence—U.S. All Ages
2002: 13.5 cases for every 10,000 women (women still on HRT)
2003: 12.6 cases for every 10,000 women (many women off HRT)
2004: 12.6 cases for every 10,000 women (many women still off HRT)
The widely reported decline in breast cancer roughly equates to approximately 1 less case (13.5 minus 12.6 = .9) of breast cancer for every 10,000 women. Some may think that’s a significant decline and others not. It really is up to you to decide.
Second, is the decline attributable to estrogen? I find it doubtful.
As I posted earlier in this thread, the estrogen only study of the WHI demonstrated fewer cases of breast cancer in women who only took estrogen. The most widely prescribed HRT in the US is a combination of synthetic estrogen and synthetic progesterone. Is it possible this decline in breast cancer (essentially one less case per every 10,000 women) is due to the absence of synthetic progesterone (MPA)? There are some studies that have reported synthetic progesterone increased the risk of breast cancer.
Some women of course do have an increased risk of breast cancer. Here’s a link to information about the risk of breast cancer. And, here’s a link to the National Cancer Institute’s Breast Cancer Risk Assessment Tool. I think it's a cool tool.
Hope that helps a little bit. I’ll try to find the info about heart disease and stroke to post as well. It's quite confounding and debatable because of the age of the women in the WHI study.
Here’s a bit more info.
As I mentioned, some people questioned the WHI data because of the age of the study participants. This abstract sums up some of the frustration. WHI risks: Any relevance to menopause management?
But, the data is being re-analyzed.Therefore the reported overall cardiovascular risks in WHI, in both treatment arms, should be regarded as irrelevant to menopause management. In contrast, breast cancer risk is relevant, providing that proper note is taken of the fact that there was no increased risk after five years of combined hormone therapy in non-prior HT users and there was a tendency to a decreased risk in oestrogen only treated individuals.
Recent Info About Heart Disease and Stroke:
The research just reported in April is trying to unravel some of the data and here’s the recent take on the risk of heart disease that includes a comment on the risk of stroke.
Early Estrogen Therapy May Reduce Cardiovascular Risks
Recent Info on Blood Clots:A new analysis of both estrogen and estrogen plus progestin data from the Women's Health Initiative (WHI) hormone trials in the Journal of the American Medical Association shows a 24 percent reduction in risk for coronary heart disease events in women starting hormone therapy less than 10 years after menopause.
The analysis, by researchers at Yale and eight other study centers participating in the Kronos Early Estrogen Prevention Study (KEEPS), also showed a 30 percent reduction in overall deaths among women aged 50 to 59 using hormone therapy.
However, the new study, "Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause," also found that hormone therapy increased coronary heart disease events by 28 percent in older women, and that deaths increased by 14 percent in women aged 70 to 79. There was a slightly elevated risk of stroke at all ages studied.
"This new analysis of WHI data seems to confirm earlier findings that estrogen may be good early, but bad late,"
New research on “blood clots” suggests it may be the route of estrogen administration that influences the risk. This research found hormone patches were far less likely to cause blood clots than pills and that micronized progesterone (bioidentical) did not increase the risk of blood clots.
Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study.
CONCLUSIONS: Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens.
Recent Info on Cognitive Functioning:
The impact of estrogen on cognitive functioning also suggests that early initiation of therapy might be important.
Estrogen, cognition and female ageing
So, in summary, the most recent research (synthetic hormones primarily)seems to suggest that initiating hormone therapy early may reduce the risk of heart disease in younger women, there is a “slight” increased risk of stroke, taking estrogen “transdermally” and micronized progesterone do not increase the risk of blood clots, and early estrogen therapy might have a positive impact on cognitive functioning.These findings suggest the presence of a critical period for HRT-related neuroprotection and underlie the potential importance of early initiation of therapy for cognitive benefit.
Connie, I totally agree with you that it’s really frustrating trying to figure it all out. I do want to say though that because the scope and duration of the research on so called natural or “bio-identical” hormones doesn’t match that of the “synthetics”, I don’t think anyone really knows if natural hormones are “safer” than synthetics, even if there is some initial research suggesting that might be the case.
Last, I’ll try to give you my perspective on steroids in another post. Suffice it to say that I basically think estrogen (and other hormones) may offer people with MS neuroprotection and steroids (synthetic “cortisol” if you will) may contribute to neurodegeneration in people with MS.
Another long post, sorry about that.
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