This Is MS Multiple Sclerosis Community: Knowledge & Support

Hi all - I just noticed that this thread has grown longer. Thanks so much Sharon for your insights and very useful info. We haven't had the chance to get the Neuro's thoughts on estriol, but we are still keen. My wife just had her first round of 3-monthly pulse steroids - only one day, but we suspect it was probably a large-ish dose.

TonyJegs - I've been reading a few of your posts with interest! You seem to be quite knowledgeable about all things MS. I never suspected that hormones and steroids were similar, and I look forward to Sharon's response to your comments. Can I ask what you would recommend someone with RRMS do? You indicated that steroids are only good for flare-ups. What about in 'normal' times? My wife can't take any of the interferons (liver enzymes) or Copaxone (allergic reaction). I assume you don't think much of these drugs anyway. And indeed, your comments about autoimmunity would indicate you don't think much of drugs like Tysabri (and immunosuppressants in general).

Most of the drugs in the MS pipeline focus on autoimmunity, but there are obviously different approaches within this class. Personally, I'm keen to see what drugs like Tovaxin and MBP8298 can do. MBP8298 seems to delay disability in SPMS, which is very exciting given the lack of drugs that achieve this goal. And Tovaxin is a bit of a mystery - but a lot of potential it seems.

There are, of course, other drugs in the pipeline which scare the crap out of me. Campath is one - the side effect profile of this sucker is interesting to say the least!

So yeah, TonyJegs, what would you recommend?

Steroids should be prohibited for use in ‘calm’ period (between relapses) or for ‘prevention’, because, when used in a long run (more than 2 weeks), they block remyelination and intensify scarification of the lesion. The same is valid for estrogens (read my post).
For RRMS the options are: proper treatment of flare-ups with proper rehabilitation after.

I’m not against immunosuppressants; I’m against their improper use. There are some forms of MS when they are favorable, but these forms are rare, about 2% of all MS.

I will post my opinion about Tysabri later, it will be negative.

Kind regards,
Tony

_________________
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer

Thanks Sharon--- extremely helpful (and encouraging ) references!

Tony,



I am waiting to hear your opinion on this.

Harry

Decline in Breast Cancer and HRT Use: Is There a Link?

HOUSTON, TX -- April 19, 2007 -- An extended analysis of cancer rates reinforces a strong association between use of hormone replacement therapy (HRT) and increased breast cancer incidence, according to research led by scientists at The University of Texas M. D. Anderson Cancer Center and published in the April 19th issue of the New England Journal of Medicine.

M. D. Anderson's Peter Ravdin MD, PhD, professor in the Department of Biostatistics, and Donald Berry, Ph.D., head of the Division of Quantitative Sciences, presented the first analysis of the 2002-2003 falling breast cancer rates at the December 2006 meeting of the San Antonio Breast Cancer Symposium. They have since examined breast cancer incidence in 2004.

In the published study, the investigators say that plummeting use of HRT in mid-2002, after results of the Women's Health Initiative study were announced, correlated with a steep decline in new breast cancer diagnoses that started shortly thereafter and continued through 2003. Incidence in 2004 leveled maintained the same low level of incidence, the lowest rate seen since about 1987, the researchers say.

The decline occurred primarily in women age 50-69, the researchers find, and was predominantly seen in estrogen-receptor(ER)-positive cancer - the type of tumors is fueled by estrogen, a hormone that is supplemented in HRT. Such cancers declined 14.7% in this time period, compared to a non-significant decline of 1.7% in ER-negative tumors.

"For our new data set, 2004, the drop in breast cancer incidence leveled off and remained low in that year, showing that the decreased rates seen in 2003 were also present in 2004, meaning that the decline was not a one-year wonder, a short-lived anomaly," says Ravdin, the study's lead investigator.

"This kind of study can't prove causality, but the data present a very compelling link between hormone replacement therapy and breast cancer," says Berry, the study's senior investigator.

Using data derived from National Cancer Institute cancer registries that report on 9% of the U.S. population, they found that the total decrease in breast cancer incidence was 6.7% between 2002 and 2003. They also calculated that by the end of 2002, about 20 million fewer prescriptions for HRT were written in the United States - a decrease of 38%. Interest in HRT use dropped after the 16,608-participant federal Women's Health Initiative study results were announced in July 2002 and showed that the risks of taking these agents outweighed the benefits for many post-menopausal women.

Ravdin and Berry strongly stress, however, that their study is not suggesting that all women stop their use of HRT. "This study is not saying that an individual woman will reduce her absolute risk of developing breast cancer by 15% by immediately discontinuing use of HRT," Berry says.

While it may be true that stopping use of HRT may have prevented as many as 14,000 breast cancers in 2003 compared with 2002, the percentage of decline is based on an entire population, he explains. "At best, based on this analysis, an individual woman could reduce her individual risk of developing breast cancer by one in 60, or about 1.7%, if she stopped using hormones," Berry says.

As a physician, Ravdin tells his patients to follow currently accepted guidelines for HRT use: to use the drug at the lowest dose and for the shortest time period to control hot flashes and other debilitating symptoms caused by the onset of menopause.

"The risk of developing breast cancer from use of these hormones is relatively small and for some women with postmenopausal symptoms, the benefits of HRT are well worth that risk," he says. "This is just another small piece of the puzzle to help women gauge the risks and benefits of using HRT."

The researchers also say that their study cannot answer three key questions: whether stopping the use of HRT leads to a permanent or a temporary decline in breast cancer incidence; if this effect is seen for stopping all types of HRT; and how much of a contributing role other factors may have played in the decline.

"There are several possibilities as to what effect stopping HRT has. Possibly, it slows the growth of tumors that are there but aren't big enough yet to be detected on a mammogram. Or it could be removing the hormone fuel stops the growth completely or even causes tumor regression," Berry says. "We don't know which is correct."

While Berry, an expert in statistics, adds that he was initially surprised that stopping HRT use could have such an immediate impact on breast cancer growth, Ravdin, the clinician, says he was not. "We know that if you treat ER-positive breast cancer with anti-hormone treatment, you can see shrinkage within weeks, so why wouldn't withdrawing hormones have the same kind of effect on smaller cancers that have not yet been detected?" says Ravdin. "My thought is that these tumors don't completely disappear, but they have stopped growing - hopefully, for many of them, forever."

As to the impact of other factors on breast cancer decline, the researchers say that one contributing factor could be declining use of mammography by women who have stopped using HRT. NCI data has reported a 3.2% decline in screening mammography in 2003 for women 50-65 years old, compared to 2000, Berry says, but adds, "such a change would seem insufficient to explain the decline in breast cancer incidence." A large drop in screening would have been seen in breast tumors that are both ER-positive and ER-negative, and that wasn't the case.

Finally, the researchers say that this study may lead to new insights into both the etiology of breast cancer and its prevention. "We will continue modeling incidence rates to try to understand whether what we are seeing is a slowing or a regressing of tumors, or a mix between these two things," Berry says.


SOURCE: The University of Texas M. D. Anderson Cancer Center

I hope you will find it useful, the numbers are impressive.
Also I wonder why your neuro said this about HRT in Europe? The strong negative effefect of estrogens were discussed there from mid 70-ties.

Kind regards,
Tony

_________________
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer

Thanks Tony-- it's a very good article. I think my neuro was talking about HRT with estriol only, which is bioidentical and the weakest of estrogens, whereas these studies looked at various combined therapies with other, synthetic estrogens.

Mmm...didn't I just mention something in another thread about male neurologists and lack of progress in MS research

mjs wrote:
I’m not at all certain what to say. I have no medical or scientific background. I’m quite certain I don’t really understand Tony’s points and objections to estrogen in people with MS. (or, why he thinks estrogen increases the risk of breast cancer since the estrogen only trial showed just the opposite).

I do think balancing estrogen and progesterone levels is important. I also think that neuroprotection and the prevention of neurodegeneration is important. I think estrogen, pre-clinically, exhibits neurprotective properties that might be applicable to people with MS. I definitely don’t have the impression estrogen and synthetic versions of “cortisol”, i.e., IVMP, etc. do the same things. I think the decline in hormone levels with age, including estrogen, increases the possibility for neurodegeneration in people with MS. So, with that…..some comments.

Estrogens and the Blood Brain Barrier

Based upon what I’ve read (and could understand a little), estrogens just don’t act directly after passing the blood-brain barrier as all other steroids do. Estrogens are also synthesized de novo in the CNS, as are several other hormones (progesterone, DHEA).

Glia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones



To repeat, some researchers are of the opinion that some steroids, including estrogen, are produced “de novo” in the CNS to cope with neurodegeneration, provide neuroprotection and support repair.

Stable MS PM

Yes, I think most women with MS stabilize in the PM period if that means the absence of relapses. My guess would be that this is because many probably progressed from RRMS to SPMS when relapses are less frequent or cease. Personally, I don’t consider the SPMS phase of the disease to be better than the RRMS phase.

Lesions, MS and Estrogen

With regard to estrogen, lesions and scarring, I have no idea how that process occurs. But some people and researchers don’t think lesions correlate well with disability, so I have to ask how relevant is that?

And, if it is relevant, there’s some information that estrogen has a positive impact on lesions in spinal cord injuries. (There may be some similarities between SCI and MS lesions).

Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats


Estrogen, Neurodegeneration and Neuroprotection

Two of the things it seems that researchers suggest may impact neurodegeneration in people with MS are mitochondrial dysfunction and glutamate toxicity. I have to resort to what Dignan once referred to as word matching, so, here’s some word matching about that as it pertains to properties of estrogen.

First, info about glutamate toxicity and estrogen.

Equine estrogens differentially prevent neuronal cell death induced by glutamate

Now, some info about estrogen and mitochondria.

Mitochondria play a central role in estrogen-induced neuroprotection

Is MS a chronic degenerative disorder that should be added to that list, or, to the list in the following abstract? Estrogen is being developed as a neuroprotective agent for degenerative neurological diseases.

Development of 17alpha-estradiol as a neuroprotective therapeutic agent: rationale and results from a phase I clinical study
If you want to read more about estrogen and neuroprotection, there’s more…..

From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens

Mechanisms of neuroprotection by estrogen

Are estrogens protective or risk factors in brain injury and neurodegeneration? Reevaluation after the Women's health initiative.


Neuroendocrine modulation and repercussions of female reproductive aging



Estrogen, estrogen treatment and the post-reproductive woman's brain



Estrogens, progestins, menopause and neurodegeneration: basic and clinical studies



That’s way more than enough. Like I said, my interest in utilizing "estrogen" to help manage MS is for it's potential to increase neuroprotection and to prevent neurodegeneration.

I’ll post some info about why I’m not fond of other steroids (namely synthetic cortisol, methylprednisolone) to treat MS at another time. Here’s just one reason why I think it’s not exactly comparable to estrogen.

Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway


I understand some people equate estrogen with methylprednisolone. Clearly, I'm not one of them. And, I do understand many people find "steroids" helpful for relapses.

Take care all...the beat definitely goes on.

Sharon

It doesn’t matter what kind of estrogen you use, the mechanism of action is the same (otherwise they will never be used at all).

Please, re-read my posts about estrogens. I tried to make it short and understandable. I usually place the core explanation in my posts, and if you get it right than it would easy to follow the subject.
When I wrote about cognitive decline in PM women using estrogens I forgot to mention that they usually experience great emotional disturbances, sometimes even OCD. The rate of epileptic seizures became greater also, opposite to usual rate decline during aging.

And remember, there is no such thing as ‘balanced HRT’, it doesn’t work either.

Kind regards,
Tony

_________________
"All truth passes through three stages.
First it is ridiculed.
Second it is violently opposed.
Third it is accepted as being self-evident."
Schopenhauer

Some refer to that as a “raging hormonal imbalance.”

Now for some news about “estrogen” and dementia from the recent AAN meeting in Boston.

Study: Hormones May Ward Off Dementia


And, more news, a poster in the imaging section of the ACTRIMS Conference being held May 30th to June 2nd is entitled:

HRT Contributes to Neuronal Health in Postmenopausal Women with MS

Sounds like more good news to me. Take care all

Sharon