Re: Men, Women and CFS

September 6, 2006

Ok, so there's a couple of things here which ring bells for me, but I'm going to

need to sit down and draw pictures to make sense of the scientific language.

This time of day it's all gobbly gook to me (well, yes any time of day, but more

so just now!). So back to the bells and stress and oestrogen. The stress bit

fits for me - long term, then shortly after CFS/MCS was diagnosed, my son died.

The doc said to me, " well that's it, no sense treating you, you'll never get

better. " Well hey thanks. Fortunately, I'm an optimist - but here I am ten years

later still sick.

Now the next bit, the oestrogen bit. I always had hormone inbalances, including

not enough oestrogen. How does that fit with your hypothesis? Now I'm taking

extra oestrogen (post menopause) and relapsed. You got me thinking, that's for

sure but I'd like to hear what others have to say, and I want to draw my

pictures in the morning, when I'm brighter. Thanks for your research efforts.

I'm impressed.

Men, Women and CFS

Hi, all.

Well, I was in the medical library most of the day, today, doing a

lot of reading and thinking. I think a few more pieces of the

puzzle have come together, and I would like to tell you about it.

By way of introduction, there have been several things rattling

around in my head lately:

First, long-time readers will know that historically on the lists I

have been beaten up fairly soundly at times for suggesting that

emotional stress could be a contributor to the onset of CFS in some

cases. I think that for the most part it has been men on the lists

who have done most of the beating. On the other hand, I have been

told by quite a few others (I think mostly women) that emotional

stress was a major contributor to the onset of their illness. It

was tempting to suspect that the men were just being macho, but what

about taking the revolutionary point of view that (a) they know what

they're talking about, and ( they just might happen to be telling

the truth? Could it be that things are different for men and women?

Second, I've been trying to figure out if I have a strong enough

case to send an abstract to the IACFS hypothesizing that I can

explain the reason for the much higher prevalence of CFS in women

than in men.

Third, has written me a couple of times asking what I have to

say about Jill 's second talk at the April DAN! conference in

which she described the " female advantage " in autism, which involves

estrogen stimulation of the methylation cycle and glutathione

production.

Well, now I think I have an answer for all of those things. Here's

the story:

When people are under stress, their sympathoadrenomedullary system

puts out epinephrine (adrenaline). Epinephrine is a catecholamine.

Normally it is detoxed (metabolized) by COMT (catechol-O-methyl

transferase), which takes a methyl group from SAMe and attaches it

to the epinephrine molecule. This de-activates it, and it is

eventually excreted. If they have a SNP in their COMT that causes

it to be less active, then the epinephrine will build up to higher

concentrations and stay around longer, which will allow more of it

to react with oxygen and form a semiquinone. The semiquinone can

react with oxygen to form a quinone and a superoxide free radical.

Normally, quinones are conjugated by glutathione with the help of

glutathione transferase enzymes, and then they are excreted from the

body. However, if the person has SNPs in the glutathione peroxidase

enzymes, then the quinones can hang around longer. There are

enzymes that convert quinones back to semiquinones, and then the

semiquinones can react with oxygen again, reverting back to quinones

and producing superoxide again, and so on. This is called redox

cycling, and it contributes to oxidative stress, which of course

puts greater demands on glutathione.

So far I've been talking about people in general. But suppose we're

talking about a woman, and particularly a woman who is in her

potentially reproductive years. This woman is making estrogens in

significantly higher amounts than men do--no surprise there! Well,

the estrogens have to be disposed of, so how does she do that?

There is more than one pathway, but it turns out that the main way

she does it is to convert the estrogens to what are called catechol

estrogens, using the enzymes CYP1A1 and CYP1B1. Normally the

catechol estrogens are then dealt with using good old COMT, which

inactivates them, and they are eventually excreted. But what if

this woman has a SNP in her CYP1B1 that raises the activity of this

enzyme, and what if, in addition, she has a SNP in her COMT that

slows it down? Well, then more of her estrogens go into making

catechol estrogens, and more of them are converted into

semiquinones, which then react with oxygen to make quinones and

superoxide ions. Well, you know the story from there on--what if

she also has SNPs in her glutathione transferase enzymes? This is a

recipe for more oxidative stress and more demands on glutathione.

O.K., now what if she is a woman in her potentially reproductive

years, and she has these SNPs, and she is under a lot of emotional

stress? Get the picture? A major overload on glutathione. Now if

she also has a set of SNPs that make her methylation cycle

vulnerable to developing a block when under oxidative stress, guess

what happens to her--CFS! Is this scenario far-fetched? No, it

isn't. I have the data on several women who fit this picture, and

you know who you are!

O.K., so what about the men? Well, they certainly produce

epinephrine, but they won't have a big competition from estrogens

when they try to get rid of it. So their capacity to handle stress

is probably going to be greater, on the average. We're just talking

about biochemistry here, not how macho somebody might be or how

tough or what kind of guts or character they might have. It's just

inescapable biochemistry. So the men are right, and the women are

right, too.

So why do women get CFS at higher rates than men do? There are more

demands on their glutathione, because of their higher production of

estrogens.

O.K., what about the " female advantage " in autism, and how does that

square with what I've said above? Well, Jill was talking

about little girls, and I'm talking about BIG girls, er... WOMEN! I

think this is a nonlinear situation. A little bit of estrogen

probably helps, because it boosts glutathione production. But a lot

of estrogen, especially if combined with competition from stress-

induced epinephrine, turns into a " female disadvantage, " because the

greater oxidative stress overwhelms the increase in glutathione

production.

Well, I'll probably get some stunning e-mails in response to this,

but that's what I've come up with today.

Rich

September 6, 2006

Dear Rich.

At the onset of my illness, at age 35, I was not under emotional stress. I was

happy with my life, swimming, dancing, working, active in my community,

culturally and Spiritually.

I got a virulent virus that would not go away and my Immune System and brain

have never been the same since.

The virus and/or immune response waxed and waned for several months. The acute

stage quieted down but the immune response and sore throats, continued to wax

and wane for several years.

By using every healing modality I was familiar with, I managed to keep going,

and progressing in the above areas of my life.

As a matter of fact, I was quite aware of 2 parallel tracks ocurring.

Healing...due to all I was doing for health, Spiritually, the rest of life..yet

" something " that felt like an active disease at the cellular/immune level.

Sometimes I thought it must be a rare disease, and other times...that I was not

excercising, eating, sleeping, thinking correctly or whatever. I would either

ignore it or take action in any of those areas.

After 4 or 5 years, and the healing work making my life even more satisfying and

promising than before...I again deteriorated in brain, pain, and energy and

immune function. In preparing for continuing education, and becasue of what I

was experiencing, I tested to see if I had learning disabilites and they said

yes. I had acquired Dyselexia seemingly from nowhere!

(BTW, I used to read 5 books at a time, but now could not get through one, or

even remember that I was reading one...I would find them around the house

later..dozens now)

During this time, I turned down a job I really wanted, I could barely find my

way home, (or have the strength to keep my foot on the brake at a stop sign), I

totalled my employer's car, I started a fire in my house that I could not

remember how to put out.

I again had acute un=resolving infections and could not tolerate sensory input,

even people talking.

I had seen several doctors who could find " nothing abnormal indicated " , would

not order an MRI, and finally suggested take antidepressants and seeing a

shrink.

What I was reporting to my family long distance and my friends was so freaky and

out of the realm of anything they'd ever heard of, they were extremely alienated

from the entire situation. After not being able work it into any physical,

emotional or mental framework they possessed, they all detached and continued to

theorize among themselves.

No one around me, and no relative known to me, living or dead had anything like

this simultaneous nightmarish set of circumstances ever happening. (Later I

discovered the identical thing WAS ocurring around my community, state and

indeed, to tens of thousands across the country.)

It was not until I went to a CFS Specialist that I was diagnosed

with Chronic Fatigue Immune Dysfunction Syndrome.

A heavy dose of Acyclovir broke the daily sore throat pattern,but nothing else.

I was bedridden usually for 20 hours a day, in excruciating nerve, muscle, joint

pain, a mudslide for a brain, in a dark quiet room for the next 4 or 5 years.

With Gamma Globulin and B-12, I would sometimes have 4 hour window when I felt

almost " normal " . That is how I managed to have any life...in those 4 hour

increments, which I made very good use of.

Stopping my personal account here...I ran a CFIDS Support Group for 10

years...the 90s. I attended the AACFS International Research Conference in 1996.

It was preceded by a Support Group Leader Conference. In my own group, and

verified by the others, we could identify no emotional component to the onset of

this disease.

Tho, other than Researchers and Physicians who specialized in CFIDS, virtually

the entire human race...friends, family, comedians, the Media, psychologists,

Neurologists, New Age practioners, INSISTED this must be the case.

Of course there were the endless

parade of multi market sales people who had THE product(s) that would make us

well (or THE Spiritual practice or THE energy work, or whatever). If we did not

get well or purchase them in the first place we " must not really want to get

well " .

The above is virtually identical experience among, now hundreds of thousands of

patients around this country. (the Planet actually...millions).

Including normal happy teenagers and children.

Meaning...the terrifying, painful and multisystemic illness with severe

cognitive impairment, within a society demanding

that we get up and get back to life. Otherwise, we must be doing something

wrong.

The difference I have personally observed between men and women is this: The men

I have known tend more to be relentlessly in pusuit of or positive that they

have found The Cause, The Fix..The Cure. ANything short of that is completly

unacceptable, and the crashes full of despair and defeatism.

Tho I am not unfamilar with the despair and defeatism of a crash after

improvement.

Of my 5 friends in my community who committed suicide, 3 were men and 2 were

women.

Others can comment more on the Science you have postulated. But I cannot verify

that more women than men were under emotional stress at the onset of CFIDS from

what I have seen, heard, or read.

There may be other factors involved in that observation...

women do generally acknowledge emotions more than men...are living a more

(acknowledged) emotional life.

I think there are statistics that say prime of life women's lives are more

stressful than men's, and not just from an internal interpretation.

(We're talking different decades of onset now also...more cultural and

environmental factors at play)

In the early research, it was sometimes said that stress the year before could

have made one more susceptible to the " hit " , assumed to be a virus. But that was

usually not said as " emotional " , per se...but any major stress to body...car

accident, surgery, major illness, chemical exposure, vaccines, blood

transfusion, excessive work, OR major life changes. I do not recall this being

gender specific, and there was still thought to be an " it " that was out of the

norm or familar to the Medical Profession.

Women do have a more complex system and hormonal differences. I think this is

related to why they have higher numbers of Autoimmune disease?

It was also thought that there might be asymptomatic " carriers " .

Since you are studying Fukuda CFS and have expressed belief in the emotional

component...it may be that women under emotional stress would be more likely to

consult with you on their cases.

CFS Specialists have said these patients (the disease) " start out complicated

and get more complicated. " There are endless opportunistic or re-activated

infections, and damage to CNS, organs, etc.

Because the CDC did not appropriately respond to the epidemic, (what was

originally meant in the US as CFS, and ME elsewhere)...or fund research, test

patients, and we have become so much *more* complicated...I do wonder if we will

ever know what actually caused onset in the first place. Even for new cases,

there is not usually informed evaluation or testing available, even for known

suspects.

On the other hand, because of the very fact that there are so many systems and

issues involved, and becasue of so many advances in the medical field, and

communication by internet, I think there are many areas, theories, treatment

modalities that can and will help us...both in actual healing/restoration and

management/quality of life and function.

By the way, in this day and age, I cannot imagine that there are very many women

or men who are not under " emotional " and every other kind of stress! including

environmentally induced.

Antidepressants, anti-anxiety, and sleeping pills are up many-fold thoughout

society.

Kudos on the time that you took to research this...and maybe something can by

gleaned for a subset of CFS, or even *aspects* for the rest of us.

Have you seen anything related in CFS Biomedical Science, or explanations for

higher number of cases among women?

TC,

Katrina

>

> Hi, all.

>

> Well, I was in the medical library most of the day, today, doing a

> lot of reading and thinking. I think a few more pieces of the

> puzzle have come together, and I would like to tell you about it.

>

> By way of introduction, there have been several things rattling

> around in my head lately:

>

> First, long-time readers will know that historically on the lists I

> have been beaten up fairly soundly at times for suggesting that

> emotional stress could be a contributor to the onset of CFS in some

> cases. I think that for the most part it has been men on the lists

> who have done most of the beating. On the other hand, I have been

> told by quite a few others (I think mostly women) that emotional

> stress was a major contributor to the onset of their illness. It

> was tempting to suspect that the men were just being macho, but what

> about taking the revolutionary point of view that (a) they know what

> they're talking about, and ( they just might happen to be telling

> the truth? Could it be that things are different for men and women?

>

> Second, I've been trying to figure out if I have a strong enough

> case to send an abstract to the IACFS hypothesizing that I can

> explain the reason for the much higher prevalence of CFS in women

> than in men.

>

> Third, has written me a couple of times asking what I have to

> say about Jill 's second talk at the April DAN! conference in

> which she described the " female advantage " in autism, which involves

> estrogen stimulation of the methylation cycle and glutathione

> production.

>

> Well, now I think I have an answer for all of those things. Here's

> the story:

>

> When people are under stress, their sympathoadrenomedullary system

> puts out epinephrine (adrenaline). Epinephrine is a catecholamine.

> Normally it is detoxed (metabolized) by COMT (catechol-O-methyl

> transferase), which takes a methyl group from SAMe and attaches it

> to the epinephrine molecule. This de-activates it, and it is

> eventually excreted. If they have a SNP in their COMT that causes

> it to be less active, then the epinephrine will build up to higher

> concentrations and stay around longer, which will allow more of it

> to react with oxygen and form a semiquinone. The semiquinone can

> react with oxygen to form a quinone and a superoxide free radical.

> Normally, quinones are conjugated by glutathione with the help of

> glutathione transferase enzymes, and then they are excreted from the

> body. However, if the person has SNPs in the glutathione peroxidase

> enzymes, then the quinones can hang around longer. There are

> enzymes that convert quinones back to semiquinones, and then the

> semiquinones can react with oxygen again, reverting back to quinones

> and producing superoxide again, and so on. This is called redox

> cycling, and it contributes to oxidative stress, which of course

> puts greater demands on glutathione.

>

> So far I've been talking about people in general. But suppose we're

> talking about a woman, and particularly a woman who is in her

> potentially reproductive years. This woman is making estrogens in

> significantly higher amounts than men do--no surprise there! Well,

> the estrogens have to be disposed of, so how does she do that?

> There is more than one pathway, but it turns out that the main way

> she does it is to convert the estrogens to what are called catechol

> estrogens, using the enzymes CYP1A1 and CYP1B1. Normally the

> catechol estrogens are then dealt with using good old COMT, which

> inactivates them, and they are eventually excreted. But what if

> this woman has a SNP in her CYP1B1 that raises the activity of this

> enzyme, and what if, in addition, she has a SNP in her COMT that

> slows it down? Well, then more of her estrogens go into making

> catechol estrogens, and more of them are converted into

> semiquinones, which then react with oxygen to make quinones and

> superoxide ions. Well, you know the story from there on--what if

> she also has SNPs in her glutathione transferase enzymes? This is a

> recipe for more oxidative stress and more demands on glutathione.

>

> O.K., now what if she is a woman in her potentially reproductive

> years, and she has these SNPs, and she is under a lot of emotional

> stress? Get the picture? A major overload on glutathione. Now if

> she also has a set of SNPs that make her methylation cycle

> vulnerable to developing a block when under oxidative stress, guess

> what happens to her--CFS! Is this scenario far-fetched? No, it

> isn't. I have the data on several women who fit this picture, and

> you know who you are!

>

> O.K., so what about the men? Well, they certainly produce

> epinephrine, but they won't have a big competition from estrogens

> when they try to get rid of it. So their capacity to handle stress

> is probably going to be greater, on the average. We're just talking

> about biochemistry here, not how macho somebody might be or how

> tough or what kind of guts or character they might have. It's just

> inescapable biochemistry. So the men are right, and the women are

> right, too.

>

> So why do women get CFS at higher rates than men do? There are more

> demands on their glutathione, because of their higher production of

> estrogens.

>

> O.K., what about the " female advantage " in autism, and how does that

> square with what I've said above? Well, Jill was talking

> about little girls, and I'm talking about BIG girls, er... WOMEN! I

> think this is a nonlinear situation. A little bit of estrogen

> probably helps, because it boosts glutathione production. But a lot

> of estrogen, especially if combined with competition from stress-

> induced epinephrine, turns into a " female disadvantage, " because the

> greater oxidative stress overwhelms the increase in glutathione

> production.

>

> Well, I'll probably get some stunning e-mails in response to this,

> but that's what I've come up with today.

>

> Rich

>

September 6, 2006

Hi Rich,

What a wonderful mind you have! We are so lucky that you would spend your time

in the library

looking up things that will help us.

My first thought is that if the estrogen/stress equation was a big one for CFS,

we would see a lot

of CFS in women who have undergone IVF treatment.

During IVF drugs are used to stimulate the reproductive system and very high

levels of estrogen

are reached.

IVF is very stressful and most cycles do not result in a pregnancy. There is a

lot of

disapointment/heartbreak.

Just a random idea.

With kindest regards,

Annette

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September 6, 2006

If men were better able to handle stress, they would be assigned the

baby-making task. I think you've got the cart before the horse. I think

woman, because the are generally able to handle stress better- and the

culture collectively knows that and expects them to carry a bigger load-do

so. They take on much bigger loads and so get sick more.

But lets not forget; women live longer anyhow.

Do those specific women you refer to have kids? You know, I think the most

sympathetic of men have a deficient idea of what it is like to be the

primary caregiver of kids-unless, maybe they are one?

A

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