The Relationship between Androgens, Regulators of Collagen Metabolism, and Peyronies Disease

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MikeSmith0

This study was published 5 months ago in the Journal of Sexual Medicine

ABSTRACT
Introduction.  Changes in collagen metabolism have been postulated to play a pivotal role in the pathogenesis of Peyronie's Disease (Peyronies Disease). Androgens such as dehydroepiandrosterone sulfate (DHEA-S) and testosterone influence collagen metabolism by modulating the activity of matrix metalloproteases (MMP) and tissue inhibitors of metalloproteases (TIMP).

Aim.  The aim of this study was to evaluate the interrelationship between androgens (DHEA-S and testosterone), key regulators of collagen metabolism such as insulin-like growth factor (IGF) 1 and IGF Binding Protein 3 (IGF-BP3), the MMP/TIMP system, and Peyronies Disease.

Methods.  Age matched Peyronies Disease patients (14) and healthy men (10) who acted as controls were recruited. Blood samples were collected from all subjects in the early morning hours after an overnight fast.

Main Outcome Measures.  Serum levels of testosterone, sex hormone binding globulin, DHEA-S, 3-α-androstanediol glucuronide, pro-MMP-1, MMP-1, MMP-2, TIMP-1, TIMP-2, IGF-1 and IGF-BP3 were measured in both groups. Statistical methods included univariate, bivariate, and multivariate regression models.

Results.  Levels of DHEA-S (114.5 vs. 169.5 µg/dL; p = 0.03), IGF-BP3 (2.96 vs. 3.79 µg/mL; p = 0.01), and TIMP-1 (173.1 vs. 195 ng/mL; p = 0.01) were significantly lower in Peyronies Disease patients. In contrast, the level of TIMP-2 (102 vs. 85 ng/mL; p = 0.001) was significantly lower in the control group. Using stepwise regression analysis, only TIMP-2 (p < 0.001) and DHEA-S (p = 0.04) were significantly related to Peyronies Disease in the final model (R2 = 0.63). TIMP-1 and DHEA-S (r = 0.55, p < 0.05) were positively correlated in the Peyronies Disease group, whereas IGF-1 and testosterone (r = −0.54, p < 0.05), and IGF-BP3 and testosterone (r = −0.68, p < 0.05) were negatively correlated in Peyronies Disease patients.

Conclusions.  Our findings suggest that decreased levels of adrenal androgens may be implicated in the pathogenesis of Peyronies Disease. The mechanism and clinical relevance of this observation remain to be established. Karavitakis M, Komninos C, Simaioforidis V, Kontos S, Lefakis G, Politis V, Koritsiadis G, Konstantellou K, and Doumanis G. The relationship between androgens, regulators of collagen metabolism, and peyronie's disease: A case control study. J Sex Med **;**:**–**.


Tim468

Although I think that this is likely to be the case, a recent study showed no correlation between patients with and without Peysonies vis testosterone levels.

The problem with such studies, though, is that they may be asking the wrong question.

If a low T level is a potential trigger in SOME men, then the absolute levels may be irrelevant when compared to men without Peyronies. I think the tendency towards increasing Peyronie's in older men, who are usually losing their testosterone, makes it hard to know. The castration studies of rabbits are very intriguing, though.

Tim
52, Peyronies Disease for 30 years, upward curve and some new lesions.

George999

Tim,  I view Peyronie's as a result of MULTIPLE coinciding factors, factors which likely occur in different combinations in different guys.  Human metabolism as you well know is EXTREMELY complex and if one thing is off that can cause trouble, when you add something else thrown off it can cure the first set of problems and create an entirely different set.  And many of these metabolic factors also active and/or deactivate specific genes which over time creates a whole different milieu.  EVERYTHING in the body interacts with everything else and as we age and/or take metabolism altering meds, lots of things can get screwed up to the point that bad things start to happen.  So I definitely think that T is a significant part of all this, but I don't think that its relationship with Peyronie's is straight forward.  I think you would find an awful lot of guys around that have longstanding T issues and resulting problems and yet die of old age without ever contracting Peyronie's.  On the other hand I suspect you would find a fair number of young guys with Peyronie's with very normal T levels.  But yet, I believe, it remains a factor, and a factor that tips the scales for some guys.  - George

MikeSmith0

Quote from: George999 on November 21, 2010, 05:31:22 PM
Tim,  I view Peyronie's as a result of MULTIPLE coinciding factors, factors which likely occur in different combinations in different guys.  

Yeah, it's got to be multifactorial... and very complex - for medicine to have gone over 200 years without a clue as to the cause.  I think a lot of diseases are this way and we're lucky we even know what we do about things like diabetes & strep throat as it is (which have a very straightforward biology).  

I also have to think it is different in different men.  If you look at all the variability, there has to be many factors.  Why do some get better when others get worse?  Why do some get it at 30 with no trauma?  Why does prostate surgery (or subsequent radiation) cause this in some men but not others?   The questions can go on and on.

The way I see it, there are probable causes on a few fronts:
- disorder of wound healing / collagen formation secondary to injury
- disorder of collagen formation - cause unspecified (perhaps unregulated immune response - but why in the penis of all places?)
- androgen / testosterone imbalances
- medication side effect (if it leads to hormone imbalance, decreased nighttime erections, altered blood flow, altered immune response)
- vascular volume shrinkage / oxygen deprived tissue / aging

If you look at the treatments that seem to be working... they seem to affect much of the above (Pentox, Viagra, arginine, Coq10, etc)

George999

Quote from: MikeSmith0 on November 23, 2010, 09:14:48 AM
I also have to think it is different in different men.  If you look at all the variability, there has to be many factors.  Why do some get better when others get worse?  Why do some get it at 30 with no trauma?  Why does prostate surgery (or subsequent radiation) cause this in some men but not others?   The questions can go on and on.

I completely agree Mike.  Its all very confounding.  And even the treatments you mention don't work for everybody.  So for sure they are impacting key pathways, but the fact that even then they don't work for all guys is a clue as to just how complex this disease is.  - George