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My Neuro is presenting the following paper at the AAN convention next week in San Diego. Interesting, given the discussions here on endocrine involvement in MS. BTW, I am a male PPMSer with low Testosterone...


[P04.103] Decreased Serum Testosterone Levels in Multiple Sclerosis

Elena V. Simon, Ilir Topalli, Amir Touray, Saud A. Sadiq, New York, NY

OBJECTIVE: To determine if serum testosterone levels are altered in multiple sclerosis (MS). BACKGROUND: MS disease severity and progression is likely affected by several factors. Hormonal changes are implicated due to a higher incidence in females, disease amelioration in pregnancy, and apparent disease acceleration in post-menopausal women and older men. Because testosterone has neuroprotective and immunomodulatory effects and is protective in experimental autoimmune encephalomyelitis, we investigated whether testosterone levels are altered in MS. DESIGN/METHODS: Total and free serum testosterone levels were obtained from 100 randomly selected clinically definite MS patients (68 females and 32 males). Patients were excluded if pregnant or nursing, taking hormone therapy or contraception, had infection, blood disorders, history of liver disease or recent steroid therapy. Patients were evaluated for disease activity. All analysis was double-blinded. Low testosterone levels were defined as 20 ng/dl in females and 295 ng/dl in males. RESULTS: Thirty-nine of 68 females (57%) and 14 of 32 males (44%) had decreased serum testosterone levels. These testosterone levels are much lower than the values seen in a normal population where only 5% would be expected to have decreased levels. A significant correlation of testosterone levels with change in EDSS was not shown in our patients. However, in male patients with ongoing disease progression, 60% had low testosterone levels suggesting a trend towards increased disease activity with lowered hormone levels. Similarly, in females with normal testosterone levels only 33% showed evidence of disease progression in the preceeding year, whereas 54% with low testosterone levels had active disease. CONCLUSIONS/RELEVANCE: Low testosterone levels occur in approximately 50% of patients with MS. In patients with low hormone levels, a relationship with increased disease activity was seen and needs to be confirmed for significance in a larger study. Treatment trials are also warranted. Supported by: Advisory Board of the MS Research Center of New York.
Category - MS and Related Diseases
SubCategory - Clinical Science

Marcstck,

Thanks for the post. Sharon our hormone guru will be pleased to see this.

The UK MS Society is holding an MS event at the end of April which includes discussions on hormone treatments as follows:

Hormone Treatments for Multiple Sclerosis: An Update.

Women are more susceptible to developing MS, and hormonal changes during pregnancy, or the use of birth control pills, reduce disease activity. Both these observations have led to the investigation of possible hormone therapies for the treatment of MS in both men and women.

Pilot studies of both estriol (oestrogen) and testosterone treatment have already shown beneficial effects. In particular, hormone treatments may be especially effective in treating both inflammation and neurodegeneration in multiple sclerosis. They offer hope for an effective oral therapy to treat both men and women with MS.

Speaker: Dr Nancy Sicotte


I'm not sure what can be done if one's hormones are low - I assume supplements. It's a pity that such trials cannot be started ASAP as the evidence points to low hormones as being a contributory factor.

Ian

Marcstck

Ian's right, I'm pleased to see this. I'm RRMS with normal testosterone levels for a woman my age. I'm no hormone guru either, I've just been fascinated since diagnosis with whether or not hormones are a factor in MS.

Here are some general links to info about testosterone and neuroprotection.
Neuroprotective Role of Testosterone in the Nervous System

One of the less known testosterone actions is neuroprotection. There are some evidences supporting the hypothesis that testosterone may act protectively in neurodegenerative disorders, e.g. Alzheimer's disease (AD), mild cognitive impairment (MCI) or depression. Androgens alter also the morphology, survival and axonal regeneration of motor neurons.........Testosterone... does not provide significant neuroprotection against glutamate-induced neurotoxicity.

Androgens Activate MAPK Signaling: Role in Neuroprotection I don't really understand all of that, but some of the more scientifically inclined might.

Another abstract on the same topic concludes:

Thus, depending on the predominance of one receptor mechanism over another, the outcome of androgen treatment may be very different and, as such, could help explain existing discrepancies as to whether androgens are protective or damage inducing.

With regard to MS specifically, there are also a couple of interesting findings about testosterone. First, that it may increase excitotoxic damage of oligodendrocytes and second that testosterone doesn't seem to help middle age mice with EAE.

Thus, my personal non-scientific no medical background take at this point is that testosterone may well have a role in susceptibility to MS, but it's less clear as to how and to what extent it might be a factor in the disease process per se.

Ian--It's a pity IMO too that trials can't be started sooner. If your hormone levels are low in the U.S. you need a physician prescription for testosterone and estrogen (estriol or estradiol). You can get DHEA and progesterone cream over the counter in the U.S., but I personally don't think it's at all smart to start taking any hormones without first having all your hormone levels checked (cortisol, DHEA, estradiol, testosterone, progesterone and melatonin) and following a physician's recommendations for supplements/prescriptions as may be appropriate in your individual case to try and achieve balanced hormone levels. It's all pretty tricky I think.

Marcstck--Please keep us posted on your neuro's research and ideas about testosterone and MS.

Ian--Thanks for the tip about the Hormone Updates planned for the UK.

Take care

Sharon

Great post, Sharon. I'm a bit concerned about the evidence that Testosterone might actually damage nerve cells, as I am on the testosterone supplement Androgel to get my levels up. Could it be that MSers bodies reduce Testosterone production to try to protect vulnerable nerve cells from it's harmful effects?
In which case I may be doing myself harm by supplementing?

Very frustrating disease...

Marcstck

To say MS is a frustrating disease is an understatement IMO. I personally haven't decided if they know less about MS or hormones.

Your questions:

Could it be that MSers bodies reduce Testosterone production to try to protect vulnerable nerve cells from it's harmful effects? In which case I may be doing myself harm by supplementing?

are definitely intriguing and I've never thought about it that way.

Generally it's my impression that atypical hormone levels (of any kind) are attributed to lesions in the hypothalamus. And, here's some info from the article Gender Issues (no abstract, just the reference)

"Hormones may show concentration effects, with opposite actions at low and high levels. Although estrogens facilitate immune responses at low concentration, they suppress immune responses at high concentrations. Sex hormones are involved in feedback loops that inhibit their own production. Links between the endocrine and immune systems are reinforced by the multiple and diverse effects of sex hormones on the immune system. In turn, glucocorticoids suppress sex hormone production and actions."

So, I'm inclined to speculate that it may be the lesions impacting hormone levels or the high level of the stress hormone cortisol suppressing hormone levels, not, in the case of testosterone, that it's the body's response to protect itself. Then again, I don't think anyone really knows.

The above quote is really one reason why I've personally opted for "balanced" normal levels of all hormones. If you're low in testosterone, I would think it should be relatively safe to at least bring your level up to normal.

Here's another quote from the same article:

"...four men who had MS and sexual dysfunction were found to have abnormally low testosterone levels, believed to be on a hypothalamic basis. The dysfunction improved with testosterone therapy."

I think the message there might be, for men and women, don't automatically assume that lesions may be interfering with sexual functioning, in some cases that might be the case, but in others it might be low testosterone levels contributing to the dysfunction. If that's the case, it may be possible to correct it with testosterone.

The article also notes testosterone's impact on oligodendrocytes (that I referenced earlier) does not explain the postulated protective effect of testosterone in MS.

So many unknowns, but if my testosterone level was low, I'd up it.

Sharon