The relationship between androgens, regulators of collagen metabolism, and Peyronie's disease: a case control study.
BACKGROUND
Changes in collagen metabolism have been postulated to play a pivotal role in the pathogenesis of Peyronie's Disease (PD). 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).


OBJECTIVE
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 PD.


METHODS
Age matched PD 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.


METHODS
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 PD 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 PD in the final model (R(2) = 0.63). TIMP-1 and DHEA-S (r = 0.55, p < 0.05) were positively correlated in the PD 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 PD patients.


CONCLUSIONS
Our findings suggest that decreased levels of adrenal androgens may be implicated in the pathogenesis of PD. The mechanism and clinical relevance of this observation remain to be established.
Karavitakis
Markos
M
Department of Urology Laboratory of Hormonology, St Panteleimon General Hospital of Nikaia, Piraeus, Greece. markoskaravitakis@yahoo.gr
Komninos
Christos
C
Simaioforidis
Vasileios
V
Kontos
Stylianos
S
Lefakis
George
G
Politis
Vasilios
V
Koritsiadis
George
G
Konstantellou
Katerina
K
Doumanis
Gregorios
G
D000368:Aged; D016022:Case-Control Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010411:Penile Induration / Q000097:blood*; D012044:Regression Analysis; D013739:Testosterone / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
D018972:Insulin-Like Growth Factor Binding Protein 3; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I