CAUSES of Peyronie's Disease - started 2005

[Liam]

There has to be something to cause it to curve.  Get it checked.  How much curve?

[tman]

There has to be something to cause it to curve.  Get it checked.  How much curve?

Probably 30 degrees.  I am scheduled to see a uro but thought I would see if anyone here had any comments.  I just cant feel anything that feels like a lump or scar tissue.  This happened about two months ago and I started taking vitamin E a month ago just in case.  Now, after the initial injury there was some pain, felt "bruised"...but it went away.

[Tim468]

Many of us have little or no palpable scar or abnormal feeling tissue (ie me). The key is for someone to recognize that your problem is real and it is not determined by whether or not they have the ability to "feel" something. If you have a new dent or area that has angulation (or both), then you have Peyronie's Disease. The lack of palpable scar is good - it means that you may have less to overcome to get better.

Tim

[Liam]

I believe you can have a lesion after an injury causing a curve without feeling it.  Glad your getting it checked.  My opinion is you can have an injury causing a curve without having Peyronies Disease.  Most others here disagree.  Regardless, penises don't curve without something making them curve.  

Good luck at the doc.  Let us know what he says.

Liam

[Tim468]

"My opinion is you can have an injury causing a curve without having Peyronies Disease."

And that would be that other disease that causes deformation after injury, right? What was the name of that again?

Tim

[Liam]

ISS or scarring or wound or penile fracture are all candidates.  This is an old discussion and I admitted this was my opinion (maybe alone) and not the majority of the other members.

Most members who have posted an opinion on this feel that any curve of the penis that is not congenital is Peyronies Disease.

I base my opinion on traumatic injuries causing a curve and never changing afterward except for improvement in some.  This is opposed to no apparent injury, but a progressive increase in plaque until eventual stabilization.  They just seem different to me.  

Maybe you would be more comfortable if someone called them type 1 and type 2 Peyronies Disease.  Maybe you would call it mild vs. severe.  WhatEVerrrr .  There's some difference.

I hope tman's gets better!  

[tman]

Thanks guys for your input.  This injury actually happened crossing a fence and my penis "rolled over" a fence spike.  I started researching this as soon as I saw that I had this issue.  I didnt have a curve for probably a couple of weeks after, of course I didnt have too many erections either because the skin on the top of my penis was so sore like you had rubbed your elbow against concrete or something.  I will let everyone know what the doc says, and in the mean time I am taking my vitamin e.  What about taking anti inflammatories?  Does anyone do that on a daily basis??

Thanks!

[Liam]

Yes, I take it for other reasons.  I think it may help.    How's that for vague.

You know, we do what we can.  

Read my House quote in the Light Side topic.  Fence spike    HELLO!!!   ***O-U-C-H***  

Is there a puncture or abrasion?  Is there a scar on the skin causing the curve?

[Tim468]

Liam: "I base my opinion on traumatic injuries causing a curve and never changing afterward except for improvement in some.  This is opposed to no apparent injury, but a progressive increase in plaque until eventual stabilization.  They just seem different to me. "

They are different, IMHO. However, most urologists would simply call both of them "Peyronie's Disease", and be grateful that they were able to identify a "cause".

Tim

[Liam]

Tim,

We are in 100% agreement on that  And, they would offer the same treatment.

[percival]

I know this might sound a very simplistic approach, but when I used to fly light aircraft, there was always a little meter which showed how many hours the engine had run so that it could be serviced at appropriate intervals.
Could it be that there is a correlation between erection hours and Peyronies Disease?
It is known that Priapism damages the erectile tissue, so what about the cumulative effect of lengthy, but otherwise normal erections and Peyronies Disease?
This could be more plausible than injury being the cause.
It might explain the large variation in distribution and age groups:  erections of short duration may be less harmful than those of the 'long haul'. Are we all victims of learning that the ' quickie' does not impress the ladies and have learned to pleasure them for hours?
It makes sense from an engineering point of view: prolonged stretching eventually wearing out the elasticity.
We could even invoke the Le Chatelier priniciple along the lines: if a system at equilibrium experiences a change in  pressure the equilibrium will shift in order to minimize that change. Admittedly, this might be a tenuous connection, but it could be that lengthy pressurisation may promote a force of resistance such as plaque build up.
Even if it were practical, it is too late for us to fit a timers to our units once Peyronies Disease has started. However, it might be that in future, all males are screened at say 3 - 5 year intervals to see if there are any markers present for developing Peyronies Disease. Action could then be taken to minimise the risk of Peyronies Disease taking hold and the current selection of drugs and supplements would probably work a lot better at this stage.
Regards,
Percival

Moved to this topic by moderator

[dahc]

My urologist speculated that the opposite was true. He thinks that older men and men that don't get as many robust erections for whatever reason are who he sees in his practice getting Peyronies Disease. He has me on half a Cialis every 3rd night and l-arginine to stimulate nocturnal erections. The cause is speculation until the medical community takes Peyronies Disease seriously enough to study it more.

Moved to this topic by moderator

[Liam]

I had the first symptoms of Peyronies Disease about 6 months prior to prostate surgery.  I noticed no change during this time.  I had two small palpable nodules, no curve, no real pain.  After the surgery and no real erections for a year, it is easier for me to find plaque than areas without plaque.  The plaque spread quickly with a vengeance.  I think a decrease in blood supply facilitated the rapid increase in plaque.  

I like the thinking by Percival, outside of the box and all.  In general, he describes a stressed system.  This may well be, at least, part of the problem.  I'm not sure about the number of hours being relevant, but it provokes thought.

Moved to this topic by moderator

[Hawk]

Percival,

I to think the evidence is strong in the other direction.  In our resource library is an article on the increase of TFG-B! with reduced oxygenation due to reduced erections.  It is the old use it or lose it principal that is still very much preached by urologists.

You must remember that priapism has nothing to do with stretch.  Where as erections gorge the penis with oxygen rich blood, lengthy erections actually interfere with blood exchange and starve the tissue.  Oxygen starvation due to 6 hour erections (with no momentary break) starve the penis in short order just as no erections starve the penis in a slow but sure fashion.

[percival]

Hawk
The point I was making was not that lots of erections might be bad for you, but that habitually holding really hard ones voluntarily for long periods might eventually lead to erectile tissue damage .
I thought of this when watching a wildlife programme: coitus amongst animals is generally a very brief affair (not that I watch beasts mating as a hobby you understand). To my knowledge, there is not an animal which matches man in sexual behavior - grinding away for hours in varying positions. Also, most animals do not have the same longevity as man. In comparison therefore, maybe we are expecting too much from the human penis considering the hammering it gets over such a long period of time!  
Someone on this forum has already said that young men should be told that the penis is not indestructible and they should learn ways to care of it. Frequent erections are of course important to maintain penile health. However, what I am suggesting is that continually striving to hold them rock hard for an hour or so to impress a lady might be a bad thing. Letting it rise and fall a few times would be better. You could even nip out any buy her a bunch of flowers during down time.
Regards
Percival

[Hawk]

Thanks for the clarification Percival, I did misunderstand your point.  I think you pose a good question and I think the information is available to give strong indications for the correct answer.

Doctors specializing in sexual medicine maintain that oxygen deprivation does not begin prior to 4 hours and in fact that erections well over that period seldom result in damage.  When you are trained to self-inject for an erection they give a packet for the local ER in the event you ever have priapism.  The first line of treatment is at home.  You are instructed to take 4 sudafed if your erection lasts more than 2 1/2 hours and to start for the ER if it persists more than 3 1/2 hours.  If there is even a momentary break in the erection then it resets the clock.

Keep in mind this is the regimen for the express purpose of maintaining healthy penile tissue after a prostatectomy so I think it is sake to say that that a 2 hour erecting with no momentary break is not the least problem for penile tissue.  If you do that all day long with only a 2 minute break every 2 hours, the penis is re-flooded with fresh oxygenated blood.

When we see that the incidence of Peyronies Disease is in inverse proportion to the frequency of erection (as determined by age, prostatectomy, diabetes) it seems clear 17 yr olds have robust healthy penile tissue because of relatively frequent, relatively long erections, not in spite of them.  Any damage would likely manifest itself quickly not cumulatively over the years.

[Tim468]

Here is more data that supports a role for TGF in causing Peyronie's Disease. My personal hunch is that those without a positive TGF finding were "burnt out" and done with the active scarring process. It would be important to document relapse or worsening later vis-a-vis TGF B-1 status.

Tim

***********************************

AU Hassoba H.  El-Sakka A.  Lue T.
FA Hassoba, Howayda.  El-Sakka, Ahmed.  Lue, Tom.
IN Departments of Clinical Pathology, Suez Canal University, Egypt. TI Role of increased transforming growth factor beta protein
 expression in the pathogenesis of Peyronie's disease.
SO Egyptian Journal of Immunology/Egyptian Association of
 Immunologists.  12(1):1-8, 2005.
AB Transforming growth factor beta (TGF-beta) has been implicated in
 many chronic fibrotic conditions such as pulmonary and hepatic
 fibrosis. Inhibition of TGF-beta activity can prevent the
 development of chronic hepatitis and mesangial proliferative
 glomerulonephritis. We postulated that TGF-beta might play a role in
 the pathogenesis of Peyronie's disease (a localized connective
 tissue disorder that primarily affects the tunica albuginea and
 adjacent erectile tissue of the penis). Tissue from the tunica
 albuginea of thirty-five Peyronie's patients (study group) and from
 eight patients without Peyronie's disease who had undergone penile
 prosthesis surgery for organic impotence (control group) were
 subjected to histological study using Hart and Trichrome stains and
 Western blotting for the detection of TGF-beta protein expression.
 TGF-beta1 protein expression was detected in 30 patients (85.7%),
 while only 8 (22.8%) and 6 (17.1%) patients showed TGF-beta2 and
 TGF-beta3 protein expression, respectively. All tissue from
 Peyronie's patients showed a variety of histological changes of the
 tunica, ranging from chronic inflammatory cellular infiltration to
 complete calcification and ossification of the tissues. The most
 prominent changes observed were focal or diffused ellastosis,
 fenestration, and disorganization of the collagen bundles. One
 patient in the control group showed fibrosis of the tunica albuginea
 and protein expression of TGF-beta1 and TGF-beta2. This patient had
 undergone surgery for the revision of his prosthesis twice. However,
 the other seven patients showed normal histologic patterns of the
 tunica albuginea and no protein expression for TGF-beta1, TGF-beta2,
 or TGF-beta3. In conclusion, TGF-beta1 protein expression is
 significantly associated with Peyronie's disease and may be a direct
 cause for its development. This finding may be of help in the
 prevention and treatment of this disease.

Moved to appropriate topic by moderator

[ocelot556]

Thanks, Tim. Keep up the good work! I'm sure it was the TGF-Beta being modified by my taking of Propecia that caused a suceptibility to Peyronies Disease. I think it was a sexual injury, but no doubt it was the hormones being modified that triggered it. I only wish my uro would have entertained the idea - maybe supported by such research - instead of dismissing it.

Moved to appropriate topic by moderator

[Kimo]

Well guys,,,here i go again...It's hit me again now for the 3rd time, i don't know whats going on this time i haven't done anything that i know of to bring this on...My first time was about 10 yrs ago which was really bad , twisted and bent like a donut,,then about 10 months ago i got another plaque recessed back in behind my pubic area, it hurt for awhile and has gotten a little smaller over the past few months, NOW, i went to a new URO this past friday and had a long over due annual checkup. He was a great doctor and i was very impressed that he was very active in peyronies research and he was impressed that i was involved with this forum...

When i was there everything seemed ok with me, [ my penis ] , i got some samples of viagra and levitra...Came home and took a half of a 20mg levitra so i could have sometime with the wife and i noticed that something was different with my penis, it just didn't look right...So thought i'd check it out the next time i took the pill again, and today i did....NOw i know what you all have described as the hour glass effect,,,but it's kinda different too..
I have this big bulge about half way up the shaft and above and below it's way smaller in girth and my penis seems shorter too....YOu know, i'm not scared this time,,i was able to have successful intercourse, but it did feel a little different.  I told the wife that i guess i was going to have to start using my VED as all of you have talked about and i need to start paying more attention to...

My penis really looked bad today, but at least i do have some feeling still...I think i will go back to see my URO and let him know whats happening.

Let me know what you all think, i do apprecieate your input.......kimo

[nemo]

Damn, Kimo, I'm so sorry to hear this.  

Perhaps now is the time to get your doc to give you a prescrip for Pentox.  Isn't that what people are recomending during the inflamatory stage?

Definitely talk to your doc asap to try to strike while the iron is hot so to speak.

Good luck, brother.

Nemo

[Tim468]

H i Kimo,

I would see if your doc us willing to do an injection to make the penis hard. It is possible that you have a "bulge" in the tunica to account for the bulge that you see. It is also possible that you have some sort of trauma to the area and had some swelling in the soft tissue that lies *over* the tunica and, when hard, was more visible. That would definintely be worth evaluating.

Also, if doing the VED, I would absolutely start with the narrow one for remodeling straight and narrow, so to speak - as that might avoid placing stress on a potentially weak area of your tunica. I would at least do that pending further evaluation by your doc.

Tim

[jackp]

Kimo
Next time that you are at the uro ask for a Doppler with an injection of PGE1 and pay special attention to the corpa. Peyronies can cause shortning of the penis and in the copra scaring that will lead to severe ED problems.
My first uro did not tell me that shortning was because of the Peyronies. I learned the above the hard way. See my post in Peyronies Surgery.
Good Luck!! let us know how you are doing.
Jackp

[Kimo]

Tim,,,Jack,,,,

I will follow your advise, i am already planning on making another appointment with my URO....Also, the VED that i have is a Osbon Esteem manual model with only one size tube and i really don't have the money to get another one....I will take it easy tho....

As far as i can remember there hasn't been any trauma as i haven't had much sex lately with the wifes health problems, so for me to have sex twice in week,,,well thats not the norm,,,dang.....

I will keep you all posted , but it will be a week or two before i can get an appt with my doc......

Thanks ,,,,,Kimo

[Kimo]

WEll , i went to my URO today and we had a great talk about things, he examined me and said it didn't look very good.  I already had a new plaque bigger than ever before. It measured 6 cm long and 1cm wide the lenght of the shaft,,,i was bulged in the middle and narrowed below and above...and i have shortened some more.  He advised me to start using the VED and to continue using viagra to help stretch things and come back in 6 months for a followup....

He is also writting me a presc. for Topical verapamil as it has helped in the past, but of course no guarantee it will work this time and i know that....I WILL have more info about this tomorrow that is different , will explain later.

He said that it could get better,,,which we hoped for,,but it may get worse and at some point he said i will need a penile implant...My plaque is so big he was very supprised and concerned. He does surgery's for peyronies and is very experienced, i was very impressed with his knowledge.

For now just keep using it as best i can and see how it goes....Will post more later.......kimo

[Tim468]

Hang in there Kimo. I will keep you in my thoughts and prayers.

Tim

[George999]

Just to steer this thread back onto topic I throw out this little thought.

Healthy human tissue requires oxygen.  Without oxygen, human cells die.  With insufficient oxygen, those same cells malfunction.  We've been down this path before.  Rico used to point it out on a regular basis.

But, healthy human tissue also requires sufficient amounts of glucose.  Glucose is the body's energy source at the cellular level.  When cells are starved for glucose, they are in trouble.  And they may have enough glucose in ordinary situations, but they may not be able to get enough glucose when they are stressed by trauma.  And when you look at the number one reason cells might be starved for glucose, it turns out to be insulin resistance.  Insulin resistance interferes with the cell's normal ability to assimilate glucose.  In fact, I would characterize diabetes as a disease which bears similarity to a man lost on the ocean dying of dehydration, glucose all around, but none available for use (which is what happens when insulin simply stops working).  I believe that this is the real culprit behind Peyronies and a number of other confusing diseases and syndromes.  If traumatized cells are unable to metabolize glucose normally in a stressed state, those cells are threatened.  And when cells start dying and malfunctioning things like plaque and cancer occur.  And once the process starts, it is nearly impossible to reverse.  Even in the best of situations, healing cannot occur in dead or dying tissue.  Healing has to progress from the healthy tissue in.  This means that barring a dramatic immune response scenario, healing takes a LONG time.  Everybody here seems to be searching for a 'silver bullet' for Peyronies.  While I certainly would welcome such an innovation and I do think the chances for it happening are becoming greater, I also think that we can all make progress right now by attacking glucose resistance.  I know that this is an unpopular subject because it goes after the stuff we love to stuff in our mouths.  As a number of people have told me, "I would rather die than give up my (fill in the blank)."  Additionally, a lot of people either just can't afford the kind of dietary changes they need to make to implement this and others are trapped by their jobs and professions.  But I am convinced that this connection is real and that major changes are going to need to happen in our society to deal with the health care crisis that this connection is fueling.  - George

[ocelot556]

George999 - My Uro asked me if I was diabetic or had a family history of it when I went for a checkup. I think you're dead-on with that assumption - I don't think it's peyronie's = diabetes, but there might be something there to the lack of insulin contributing to the scarring. Type II, however, which is resistance to insulin rather than a lack of it, has been proven to be reversed and in some cases resolved through diet and exercise. I wonder if we have a cross-section of active and inactive people, here - it'd be interesting to see if the active ones respond better to treatment.

[roadblock]

Interesting study...

http://www.ncbi.nlm.nih.gov/pubmed/17686962?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

How many of us are overweight? I'm not certain that a correlation can be made between obesity, elevated leptin and Peyronies Disease...afterall, we are not certain that tgf beta is truly pathogenic factor. This particular study was focused on a certain type of tissue fibrosis which may not necessarily translate, but certainly we keep seeing tgf beta and fibrosis linked together.

I would be curious to see a poll of the members here trying to determine if the majority of us are overweight based on BMI and if our obesity % is different than the national average.

For those of you who would like to know your BMI, here is a calculator...

http://www.nhlbisupport.com/bmi/

It is not a perfect tool but it is at least a measure of some sort. No matter what, there are numerous benefits to slimming down...this may just be one more that probably appeals to each of us if it could result in any slowing of this horrible process.

Hope everyone had a wonderful Christmas and best wishes for the new year!

roadblock

[George999]

roadblock,  The more one pours through the research, the more you find these ominous linkages.  They are everywhere.  For example, I was just reading yesterday about a phenomenal substance found in the body that serves to break down fibrosis.  What causes it to be depressed?  Why ... elevated levels of insulin!  Duh ... It all becomes a huge circular process.  Excessive body weight is an incubator for fibrotic disease in a thousand different subtle ways.  So, in our society today we see growing BMIs and growing numbers of people afflicted with fibrotic diseases.  When you look at the third world, you see that these are just the type of diseases that are following our western style fast food restaurants and dietary habits into countries that never knew these problems before.  Is there a connection?  Count on it!

At the core of fibrotic diseases, one finds AGEs.  These are proteins that are part of the body's extra-cellular matrix that have been modified by glycation (the joining of a protein with glucose).  These proteins then get 'stuck together' in a fibrotic mass AND they generate copious amounts of TGF-beta-1 AND free radicals that power the whole process forward and in turn, create more AGEs.  This is an attempt at a very over simplified description of the fibrotic process, but it nonetheless, hopefully, gives a picture of how TGF-beta-1 is involved in that process.  - George

[Tim468]

Hard to know where obesity fits in. I got Peyronies Disease when my body fat was measured (using caliper estimates from four spots) at 9%. My aerobic capacity was at the 99.5th percentile for my age (30, I think I was). Yet I got Peyronies during that time of my life. Certainly, though, now it is getting worse, and I am now long away from 9% body fat!

To see how much those of us who are overweight, look at this website by the CDC. If you simply watch the map (you can also click on a link to watch the PowerPoint presentation), you will see a 21 year record of obesity trends in America. It is shocking, and I will remind you that the projections are now saying that 30-50% of kids born in the year 2000 will develop diabetes.

http://www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm

The changes in diet and to an extent, activity, are now coming back to haunt us. Interestingly, our free market system promotes such changes (cartels of mega-monster food production giants like McDonalds, with vertical integration of basics, processing, shipping and presentation in the market) such that our diet is changing all the time - for the worse.

We are working harder and making less money, and that translates into less time to cook good foods (or to go to a local market to buy fresh produce that is not covered in chemicals).

The changes are not overhyped - look at the damn map if you doubt what I am saying! We are going fast down hill in our health, and seem powerless to change it - except on a personal level. The lowest socio-economic status groups are suffering worst, for a lack of access to good food, better information, or the time to take care of themselves.

So, I continue to make small changes and to try the good advice I have gotten here from George, Rico, etc about the value of exercise and good diet. Although a nagging voice reminds me that when I ate best and was the most fit, this disease started, I also know that my overall health will benefit, and I may slow down the progress even if I do not reverse it.

Tim

[George999]

Hard to know where obesity fits in. I got Peyronies Disease when my body fat was measured (using caliper estimates from four spots) at 9%. My aerobic capacity was at the 99.5th percentile for my age (30, I think I was). Yet I got Peyronies during that time of my life.

Tim, I think there IS an answer to this conundrum.  And that answer has to do with the concept that Peyronies at its root is glucose driven.  And what one has to realize is that a person can be VERY fit and STILL have high DYNAMIC glucose levels.  Traditional blood sugar tests measure only fasting serum glucose, NOT dynamic serum glucose OR insulin levels.  Some people, genetically, just have very robust insulin producing capacity, which means that 1) they are subject to damage inflicted by humongous spikes in insulin, 2) they are capable of withstanding wide swings in blood sugar levels which 3) will be pretty much guaranteed to have returned to grossly normal levels at the point of a traditional fasting test.  I would further suggest that this untested dynamic factor is just one reason that traditional tests of everything from serum glucose to cholesterol are not the be all and end all in terms of predicting the future.  Additionally, I find it interesting that there are some pretty arbitrary guidelines for establishing the presence of metabolic syndrome.  Yet it is also clear to me that metabolic syndrome doesn't start the second, minute, hour, day, week that some test reveals some number going over an arbitrary threshold.  Certainly, by that point in time, the process is long established and loaded with forward momentum, which makes it even more difficult to deal with.  But we are saddled with a medical system that is basically attuned to treating symptoms rather than promoting prevention, and that is why we are stuck with the mess we are all stuck with today.  And, as you very eloquently point out, our whole system as a society, and increasingly as a world, is geared to sending us hogtied down that road.  Our food supply is tailored to it, our job constraints are tailored to it, our medical system is tailored to it.  It takes a powerful lot of determination to try to buck that trend.  But I am convinced that even little steps in that direction will bring huge rewards.  They already have for me, I've tasted of it, and thats why I'm not stopping here.  - George

[Hawk]

Like Tim, I was a fit machine when I got Peyronies Disease, however, in my case I had a prostatectomy which is a known factor.  However (again),  my Peyronies Disease was not until 9 months after my prostatectomy and Dr. Mulhall told me that was too long to be causative factor.

When I got Peyronies Disease I was on a nutritional diet to fight cancer and had been on one for well over a year.  Very low in on glycemic index, many small meals, etc, etc, etc.  You would be hard pressed to recommend a diet component for glucose control and anti-inflammation I did not incorporate.  I think it is almost impractical to think that 1% of the population would be more disciplined or more informed than I was.  I certainly cannot imagine I was insulin resistant.  I was also supplementing with ALC 3.5 grams per day, mixed Vit E, high doses of C, alpha lipoic acid, high omega 3 fats, and much more.

[George999]

Hawk, I certainly have to admit that I don't have an answer in your case.  For sure you were doing everything right.  I would say that it is well known that smoking is the primary cause of lung cancer.  But some people who never smoke DO get lung cancer.  However, we now know that exposure to second hand smoke CAN cause lung cancer.  But a few people who have never really been exposed to even second hand smoke get lung cancer.  And to top that off, some people who are chain smokers from their teens remain healthy to 100.  So who knows.  But the occasional exception does not invalidate the rule.  We ALL have glucose in our bodies, even if it is a normal or even less than normal levels.  And that glucose "wants" to inappropriately bind to proteins causing fibrosis.  Fortunately, we also have systems in our bodies that work to prevent that nasty phenomenon.  But a multitude of things can go awry.  The most common by far is an environment with excessive glucose.  We KNOW that this is a risk factor because diabetes demonstrates that it is.  But there have to also be less understood factors like, perhaps, the failure of the body to produce an adequate amount of L-Carnosine, since L-Carnosine is one of the primary gate keepers in preventing glycation.  A deficiency of L-Carnosine, even in a normal glucose environment could conceivably cause glycation and localized fibrosis.  On the other hand, I am sure that there are those who can have a terrible diet and never exercise and still remain fit and healthy due to spectacular genetics and never get Peyronies or any other fibrosis disease.  But again, there is more than enough evidence, in my opinion, to implicate the glycation process, and there are enough possible explanations as to why there can be various alternative scenarios which precipitate fibrosis or even preclude it.  But the potential solution is the same.

Obviously, if the diet is already covered, and yours sounds good to me, one has to look at the potential benefit of supplementation and the VED and all the rest.  A few days ago, on another thread, Tim asked me about my diet.  I shared it simply in answer to his question.  I did not intend it to be THE model diet.  I myself am continuously adjusting my own diet.  I am right now faced with the realization that I need to take a second look at cheese.  Cheese=Saturated Fat.  There is simply no way around that, and if I look objectively at my current diet for ways to improve, cheese will have to go.  I think it is like that with all of us.  On the other hand, we all live in an environment of different peripheral health issues, meaning that what is good for one may not be good for another.  I am constantly looking for healthy things to add to my diet and less than healthy things that I really would be better off without.

The same is true of supplements.  I am constantly asking myself "Why am I taking this supplement?".  So I am constantly quiting the stuff that I no longer have a valid reason for taking whether that is because the problem has gone away or perhaps new research indicating that the stuff is really not that good after all or even moving on to something more promising.  But without understanding as much as possible about the underlying process and pathology, we are traveling without a compass or a map.  We have to base our decisions on the research and when things don't seem to make sense, we have to reexamine our logic.  I think that the whole inflammation factor is a valuable key to dealing with Peyronies.  But then you discover that underlying inflammation is oxidation, nitration and glycation.  One of the best natural anti-inflammatories out there as far as I am concerned is Mangosteen.  But then you find out that Mangosteen contains Xanthones.  And one of those Xanthones is Garcinol.  And Garcinol just happens to be a potent anti-glycant.  The bottom line is that if you strangle the oxidation, nitration, and glycation, the inflammation goes away.  There is just a lot of useful knowledge in all of this, even for people like yourself who have had the diet and exercise part down from the beginning.  - George

[Tim468]

George, I think that you are on to something, but I do not think that you are onto THE thing (well, maybe you are after reading your post to Hawk).

When I got Peyronie's I was not just fit, but I ate amazingly healthy foods (more or less). Certainly my fasting glucose was low, and I did not show much evidence of hyperglycemia (I cannot recall if I looked for a hemoglobin A1C to measure glycation).

So, for me, it doesn't seem likely that I was hyperglycemic than. I was off the grid a t a hippie college in Washington state, eating Miso soup for lunch and sprouts for dinner.

Tim

[George999]

Tim, I am not sure if we will even live long enough to be onto "THE thing", but I do believe we ARE getting closer.  I think that understanding the role of TGF-beta-1 was important and helpful, for example.  Each new step of understanding brings us a little closer, closes a few more gaps, and opens more possibilities for POTENTIAL intervention.  Will any of those potential interventions be effective?  In all honesty, I don't know.  But I think that even the most effective intervention around today would take a substantial amount of time to demonstrate its effectiveness which really throws a wrench into the try it and observe the results type of approach.  Therefore, I choose to wrestle with the underlying theories and choose my poisons based on those indicators.  And at this point that is serving me well.  Both on the mind and body side, it is only getting better for me.  So are there more revelations coming that pull back additional layers?  Of that I have no doubt, and I look forward to the day, but for now I have to work with what I have and I am intent on sharing that knowledge as well.  I am also hopeful that you all will continue to punch those ideas around and not be afraid to critique them ruthlessly.  I would be the first to admit that I have been dead wrong before on multiple occasions and on many occasions, while not necessarily completely wrong, far off the track.  And I thank all of you who have been gracious enough to set me straight on those occasions, I suspect sometimes without even realizing it.  And I always try to make an effort to go back and modify my prior posts at times to make sure that no one groks them with Google only to be sent on a snipe hunt.  In any case, Tim, I appreciate you so much, and Hawk, and all of the rest of you and wish you the very best in this New Year ahead.  Hopefully it will be a year in which we all can cut new ground, one way or another in regards to eliminating this debilitating disease!  The very best to you all.  - George

[George999]

Since Carnosine has an important role in preventing glucose from binding to the protein on the surface of our cells, a deficiency in Carnosine could theoretically lead to glycation and fibrosis even in the absence of hyperglycemia.  Dietary sources of Carnosine come almost entirely from meats.  Thus a diet unusually low in meat products (all meat, including fish), without external Carnosine supplementation, could provoke fibrosis via this route.  It has been speculated, but never proven, that vegetarians and vegans have chronic Carnosine deficiencies.  What IS known is that typical Carnosine levels vary widely amongst the general population and since Carnosine is literally the teflon that protects cellular protein, one has to wonder as to the adverse effects this might cause.  There is a delicate Glucose v Carnosine balance here and since both of these factors can vary widely in a dynamic fashion, that leaves lots of room for things to go wrong in different ways.  What is also known is that Carnosine is literally Beta-Alanine + Histodine, BUT it is also known that supplementing with Beta-Alanine + Histodine DOES NOT give the positive Carnosine benefits that supplementing with Carnosine itself does.  Since the body manufactures Carnosine from  Beta-Alanine + Histodine, the reason for this strange thing is a mystery.  But looked at critically, it could potentially answer questions as to why some of us get sick and others don't. - George

[Hawk]

I know there is nothing new about the strong suspicion that Peyronies Disease is possibly an autoimmune disorder but this is the first I have seen this study.


The Study: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7XMT-4HM78DC-R&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=740aa186b244baa0a5a2554e784b4261

This study shows a positive association for the HLA class II antigen HLA-DQ5 with Peyronie's disease, suggesting that HLA-DQ5 is a risk factor for Peyronie's disease and implying an autoimmune etiology for this disorder.

[Tim468]

I thought I posted that one before Hawk. At any rate, the association is extremely weak - not nearly as strong as some other problems with HLA associations.

Tim

[George999]

While I absolutely DO NOT believe that Peyronies is a RESULT of an auto-immune response, I would not be surprised if the kind of pathology going on in a typical Peyronies setting would kick up an auto-immune response.  After all, you have a mass of terribly abnormal tissue kicking out TGF-beta-1, scads of free radicals and who knows what all else in terms of abnormal chemical and/or neurological signalling.  As a result, you could well end up with an auto-immune response to top that all off.  A big part of the whole question in these circular situations becomes the chicken and the egg factor of which comes first.  I am absolutely convinced that this whole phenomenon is triggered initially by the inappropriate binding of glucose and protein.  Whether that is a result of excessive glucose or insufficient L-Carnosine may vary from one individual to the next, but this whole dynamic is so delicate that once the ratio of glucose to L-Carnosine (and what ever other protective agents might be involved) reaches a tipping point, the whole house of cards comes crashing down with even the slightest trauma and fibrosis sets in.  This all happens at the molecular level and results in all sorts of abnormal phenomena at higher levels, any one of which can be identified as potentially "the problem".  But my perception is that the real problem is taking place far below anywhere that anyone seems to be looking.

To further visualize this, imagine cells covered with teflon coated velcro like protein that normally allows them to cling to one another in a very flexible, at times elastic fashion.  Then imagine injecting superglue into that velcro, as in the case of too much environmental glucose, or alternatively an insufficient supply of teflon.  The result is like injecting superglue into the velcro.  Thats what happens with Peyronies.  And at that point, unless you can 1) dissolve the superglue, or 2) Cause the cell(s) in question to shed and replace the velcro, you are stuck with this mess.  Thats a simplified model of the underlying problem.

- George

[Hawk]

I thought I posted that one before Hawk. At any rate, the association is extremely weak - not nearly as strong as some other problems with HLA associations.

Tim

Actually, you are correct Tim.  A search reveals you did post that.  I either somehow missed it, or more likely it was a matter of not not giving it enough time to grasp it and therefore not retaining it.

[Tim468]

George,

When I combine searches for "HLA" and "advanced glycation end product", I only get six hits in Ovid and PubMed, none of which are relevant. I am not sure I see a way for AGE products to change HLA typing.

Tim

[j]

I sometimes wonder why there's so little discussion of the obvious genetic factor. The link between Peyronie's and Dupuytren's is well known. And the genetic basis of Dupuytren's, originating in northern Europe and apparently spread by the Vikings, is also documented. I read, years ago, that in England Dupuytren's used to be known as "Vikings' disease".  Shouldn't we be studying Viking relics, looking for straightening devices carved out of walrus tusks?

 

[George999]

Tim, Please understand, I am not claiming that there is any shred of scientific data supporting this, I am only suggesting that I can see how it MIGHT happen.  Certainly I have not identified any specific pathway for that, rather I just am convinced that these AGE entities are capable of all kinds of weird side effects that are not currently understood or identified and that an auto-immune response MIGHT be one of those.  But I CERTAINLY don't believe that Peyronies is initiated by a random autoimmune syndrome.  At least not at this point.  Of course, I reserve the right to change my mind if convincing evidence emerges to the contrary .  After all, this whole understanding of glycation and AGEes is just now emerging, and there is not a whole lot of research on it at this point, but it is being intensely studied in relation to diabetes and I suspect that by the end of 2008 we will know a lot more.  As for the auto-immune aspect, it would seem that it would be rather simple to give a Peyronies sufferer a course of immune system modulating treatments and observe the response.  I suspect they would have literally no effect one way or the other on the Peyronies symptoms.  And of course, all of this HLA stuff gets into the area of genetics, and I believe that genes and gene expression are actually far more dynamic than most people think.  I believe that one can literally CHANGE their genes in a positive way through targeted environmental vectors.  Perhaps only a few of them at this point, of course, and not easily.  Alternatively, I believe that pathogens can cause detrimental changes in our genes, but that is probably more widely accepted.  - George

[Tim468]

J,

The genetic basis is often unclear in disease. Not knowing what to do with the information is a second roadblock to using the information. We may have genetic tendencies such as abnormal wound healing, but the central questions is "Why right there??" I would not mind very much having to deal with a contracture of, say, the forearm skin. A tightening up of the skin under my neck in my fifties would be timely, not bothersome!

George, the thing I am trying to say is that HLA or autoimmune disease is hard enough to understand on my best days, but it can certainly be modified by environmental factors. The low R-value of the study (which correlates more tightly in a linkage the higher it is) suggested to (I cannot recall) either the authors, or editorial reviewers, that there would likely NOT be an answer in immune modulation. There have been sporadic reports over the years of attempting to do just that - foremost is oral or injected steroids - without the desired effects.

The R-value was something like 1.9 or 3.0, whereas other more tightly linked autoimmune diseases have Rvalues of, say 25.

Tim

[George999]

j, I think another problem is trying to separate genetics from societally typical environmental factors or even familialy typical environmental factors.  These kinds of things can really cloud the whole picture when given a genetically "pure" culture like the Vikings.  How do you discount that possibility that there might have been something unique about their diet that contributed to the issue, for example.  One could go on from there.  And if you do find a link, what do you do with it?  I think the answer is that you do the same thing with it as you would if you didn't have that information in the first place, so why even go there?  The challenge is not to identify genetic weaknesses, we know those are there, the challenge is the formulate a response to those genetic weaknesses.  Oh, I know, there are those suggesting that such knowledge would open the door to large scale genetic engineering as in "stick a corrective measure into a vector (such as a virus) and fix the problem, but I am not sure this is something that is going to happen very soon for Peyronies.  So perhaps for some things it makes sense, but not for Peyronies in my mind.  Those are my thoughts babblings on the subject.  - George

[j]

I'm a software engineer. When faced with a software bug, productive effort focuses on identifying the root cause - the exact, specific error in the code.  Attempts to correct a problem without really understanding it are called "hacking" and and typically introduce new problems while masking old ones.   Under pressure of time, the temptation to start "hacking" in hopes of making the bug go away is often irresistable; but the top guns are the guys who ignore the noise and go deep right from the start.

I am not saying we shouldn't try to "hack" Peyronie's disease because obviously any partial relief is a win; but the genetic factor is an elephant in the room.

[George999]

j, The human genome is extremely complicated.  Identifying THE root cause is extremely unlikely.  It is far more likely that there are multiple genetic weaknesses which might contribute to susceptibility to Peyronies either individually or in combination.  It is also extremely likely that a person with zero of these genetic weaknesses might be very susceptible to Peyronies in a given environment.  I certainly have no problem discussing possible genetic aspects on this forum.  But you are going to have to come up with far more than what you have so far to wring anything useful from that aspect, and don't get me wrong, I am all ears.  And certainly, the more ground we cover, the more opportunities we will find, so if genetics turns you on, go for it.  - George

[j]

There's nothing you or I could do with this information except use it to condition our expectations.  Speaking for myself, I've accepted that I have a genetic anomaly, which reduces the chances of success from something like diet or supplements. Yes, there could be all sorts of interactions with environmental factors, but the bottom line is, I have a malfunctioning gene and I can't change that.

Genes code for proteins.  As the genetic basis of other diseases have been unravelled, researchers have been able to identify the proteins in question and build a model of what's really going wrong, starting at the beginning of the chain - a big step towards a treatment.  

I guess what I am saying is that I'm mostly unimpressed by the Peyronie's research I've seen to date, as it isn't targeting the root cause. I'm not aware of any research into the genetics of Dupuytren's/Peyronie's, although it could certainly be happening. Instead we have treatments based on hunches and guesswork, and none are panning out. This is what I call "hacking" and one of the bad things about hacking is that it diverts energy and resources from the slow, difficult but ultimately more productive work of finding the real problem.

If, starting 10 years ago, all the money that's been blown on unproductive treatments - verapamil, iontophoresis, crude surgical corrections, vitamin E and "followup" office visits, pentox, the whole list - had been directed to serious work on the genetics, we might be in a better place today.  

This is just a rant - I don't have a solution.  It's the way our system works, or doesn't.  Maybe in a perfect world, if I contacted a urologist about Peyronie's, he'd be prepared to say "sorry, we don't have a solution for you at this time. Instead we're suggesting you contribute to an ongoing research project...."  Instead, you follow the White Rabbit down the hole and start spending money on office visits and Transdermal Verapamil - or get loaded on a conveyor belt to surgery...

[pal-31]

I think part of the problem for not spending the $$$ on research into the root cause is all these missconceptions and false statistics that one keeps hearing from Physicians and Urologist all over the place. The idea that Peyronies Disease effects less than 1% of the male population, that 1/3 to 1/2 get better without treatment, and that it is not life-threatening and therefore not important.

I think once more studies and data is available on the rate of males effected, and how in most cases Peyronies Disease does not get better on its own, not even with treatment, and the effects it has on couples and families, then we may see more and hopefully better research.

Actually if the drug companies find out the real percentage of men effected and the potential $$$ to be made then we'll get somewhere.

sorry ..that was just my rant  

Pal

[George999]

the more we will learn about Peyronies.  That's the real secret of moving this thing forward.  Certain types of fibrosis are getting big money these days.  Fibrosis of the kidneys, liver, and lungs for example.  And the more we are learning about those, the more we are seeing how much they have in common.  So we can very likely take that information and apply it to both Peyronies and Dupuytren's NOW without having to wait forever for Peyronies research.  That is where the goldmine of data is that can help us move forward right now.  - George