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Hi,

could someome please help me to understand the results of that study, I think I have problems with the translation:

Link PubMed

RESULTS: Serum testosterone was significantly lower in women with MS than in controls. The lowest levels were found in women with a greater number of gadolinium enhancing lesions. A positive correlation was observed between testosterone concentrations and both tissue damage on MRI and clinical disability.
In men, there was a positive correlation between oestradiol concentrations and brain damage.

The way I understand it one sentece confilicts with the other:
When women with lower testosteron have a higher lesion cound and higher disablity, then this would not be a "positive correlation", but a "negative correlation".


How about men? Does the study say that the higher the oestradiol, the higher the brain damage (ie lesion cound / atrophy etc).
That would contradict the findigs of this study:
Link PubMed


Thanks!

--Frank[/b]

Hi Frank,
In the first abstract, when referring to women

A positive correlation was observed between testosterone concentrations and both tissue damage on MRI and clinical disability.

the "positive" means "yes" there is a correlation. The word "positive" doesn't refer to testosterone levels themselves.

When referring to men, the first abstract states that there is a correlation between oestradiol concentrations and brain damage but doesn't mention if the correlation is due to low or high levels.

The second abstract doesn't mention the word oestradiol so in that regard there is nothing contrary BUT they purposely point out this information which is contrary with the first abstract

Unlike previous studies, we observed that testosterone levels were significantly increased in MS females and did not correlate with disability.

Bob

Thanks Lyon, for your answer.

the "positive" means "yes" there is a correlation. The word "positive" doesn't refer to testosterone levels themselves.

I found that
definition of positive correlation:

Positive correlation indicates that both variables increase or decrease together, whereas negative correlation indicates that as one variable increases, so the other decreases, and vice versa.

So positive correlation means either both parameter rise together or both parameters drop together.
Taking this I would still say that there is something wrong with the first abstract concerning the testosteron in women.

When referring to men, the first abstract states that there is a correlation between oestradiol concentrations and brain damage but doesn't mention if the correlation is due to low or high levels.

The same is with men and estradiol. If these two parameters have a positive correlation then it should be:
Low estradiol results in low damage.
High estradiol results in high damage

BUT they purposely point out this information which is contrary with the first abstract

The second abstract explicitly says their findings for testosterone levels in women are unlike previous studies.
My original thought was that the two studies contradict in the findigs of estradiol in men.

--Frank

Frank

I think the information from these studies may be difficult to understand simply because the findings from the second abstract aren’t all that clear. From my layperson’s perspective, the findings from that study are better described in news articles such as this one:

Compared with healthy women, those with MS had lower levels of the male hormone testosterone

And those with the lowest testosterone levels also had the highest amount of inflammation in their brain tissue, expressed as the number of gadolinium enhancing lesions.

Women with MS and abnormally high testosterone levels also had greater levels of brain damage and a trend towards increased disability.

Among men, there were no differences in testosterone levels between those with MS and the healthy group.

But men with MS and the highest levels of the female hormone oestrogen also had the greatest degree of brain tissue damage.

In contrast to those MRI findings, the first study you posted correlated low levels of estradiol in men with disability levels so it’s perfectly understandable why you’d think the findings with respect to estrogen levels in men was contradictory.

But, exactly how contradictory they might be is open to question I think, especially if you consider three other factors:

1. Women with MS generally have more inflammation than men but less severe disease, so a finding of increased inflammation on MRI in men with high levels of estrogen may not correlate all that well with disease progression and disability, and

2. Lesions themselves do not correlate all that well with disability, and,

3. Estrogen displays significant neuroprotective properties in pre-clinical research.

I’d add, as Dom posted earlier in another thread, I find the correlation of low estrogen levels in men with disability a more significant finding than the MRI findings.

Last, just a note about “causality”, from the journal article (which is freely available but you have to register with the journal) focused on MRI findings:

“determining whether increases in serum hormone levels reflected the brain’s compensatory repair mechanisms during injury or if these molecules actually contribute to the development of tissue damage was not possible,”

Now, I hope I haven’t confused things even further. The research on hormones and MS is just in its infancy and high and low levels of several hormones have been associated with a variety of disease measures, so one thing to consider is having your hormone levels tested to be certain that they’re within the normal range. As an aside, in the small testosterone trial, the men had low normal testosterone levels and their testosterone levels remained within the normal range even with the dosing that was used.

Take care. I’m so glad to see from another thread that you’re doing so well.

Sharon

Sharon, thank you for your explamations.

Actually my GP adviced my to supplement DHEA to bring my level in the optimum range.
But in his opinion the exclusive increase of DHEA will most likely not be sufficent to bring the testosteron and estradiol as much up as needed.

He also thinks that, as DHEA is a precursor, the body CAN transform it to other hormones if they are needed which would be good to avoid sideeffects from too high hormone levels.

I have an appointment with my neurologist on the next weeks tuesday and will discuss my hormone levels with him. Maybe I want to get a third opinion from an endocrinologist before I'll actually start to supplement testostrone and estradiol.

To engage with the hormone-system makes me somewhat worried, so I dont want to rush into it.
On the other hand hormones play a crucial role in may major metabolic processes so it would surely be good to have them within optimum levels.

--Frank

Frank

It sounds like you’ve educated yourself quite well on the topic and have a GP who knows something about hormones too. I think you’re being very wise to be cautious about supplementing with hormones.

I haven’t seen an endocrinologist for a “third opinion” but definitely think it’s a good idea. I’ll be curious about your neuros recommendations for supplementing hormones to optimal levels and if you proceed with the third opinion, whether or not the endocrinologist considers evaluating your adrenal functioning.

Per this abstract people with MS may have a dysfunction in DHEA secretion and they found an association between the EDSS score and cortisol/DHEA ratios.

Besides that study, it seems that several high and low hormone level findings in people with MS involve hormones that are primarily produced by the adrenal glands, i.e., it’s my understanding the primary source of cortisol and DHEA in both men and women is the adrenal gland, and that it’s also the primary source of testosterone in women and estrogen in men.

I find it all pretty interesting, especially since a major susceptibility locus for MS is on the 6p21 chromosome that’s also associated with cortisol biosynthesis .

Given your interest in immune modulation, you might also be interested in this abstract about DHEA and T regulatory cells.

Take care

Sharon

Very interesting articles, thanks!
Indeed an increase in FoxP3 regulatory cells might be the best way to keep the immune system from exaggerated reactions.

I will give an update when I've talked to my neuro on tuesday...

--Frank

I have visited my neuro today.

He adviced me to have my hormone-levels tested again in eigth weeks to see whether they are constantly low or it just was a transient state.
If they keep low he supports the idea of supplementing testosteron and estradiol.

--Frank

Sounds like an interesting study Frank. Thanks for being the guinea pig!!

Bob