Asian J Androl 2008; 10 (1): 79–87
Non-surgical therapy of Peyronie’s disease
Department of Urology, Rush University Medical Center, Chicago 60612, USAAbstract
The present paper provides a review of the available non-surgical treatments for Peyronie’s disease (PD). A
review of published literature on oral, intralesional, external energy and iontophoresis therapies for PD was performed,and the published results of available treatment options reviewed. The authors’ recommendations for appropriatenon-surgical management of PD are provided. Although there are many published reports that show the efficacy ofnon-surgical therapies for PD, there is a lack of large scale, multicenter controlled clinical trials, which makes treat-ment recommendations difficult. Careful review of the literature does suggest that there are treatment options thatmake scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offeringno treatment at all will encourage our patients to pursue alternative treatments, which might do harm, and misses theopportunity to do some good. Clearly further work is necessary to develop safe and effective non-surgical treatmentsfor PD. (Asian J Androl 2008 January; 10: 79–87)Keywords: Peyronie's disease; penile induration; humans; injections intralesional; vitamin E; pentoxifylline; amino acids 1 Introduction
formation of hypertrophic scars. Recent investigationshave focused on the mechanisms of wound healing,
Peyronie’s disease (PD) is a psychologically and physi-
fibrosis, scar formation as well as scar remodeling, and
cally devastating disorder that manifests as a fibrous in-
have correlated their findings to the Peyronie’s population.
elastic scar of the tunica albuginea, causing penile
Study of the molecular etiology of PD has unearthed
defor mity, pen ile cur vatur e, h in gin g, n ar r owin g,
several important growth factors, which can be divided
shortening, and painful erections. Despite multiple treat-
into profibrotic and antifibrotic groups. Profibrotic fac-
ment options offered since Francois de la Peyronie de-
tors include TGF-1, which is an activator of collagen I
scribed PD in 1743 , this disorder remains a consi-
synthesis , and which is released by neutrophils and
derable therapeutic dilemma to practicing physicians.
macrophages during the acute and proliferative phasesof wound healing. El Sakka et al.  found that in PD
plaques, TGF-1 protein expression, as measured byWestern blot, was overexpressed as compared to controls.
Contemporary thinking would considers PD as a dis-
In addition, TGF-2 and TGF-3 expression was not
order of wound healing, and as such it is similar to the
enhanced, suggesting that TGF-1 overexpression mightplay a role in PD development. Subsequently, TGF-1 wasused to induce PD in a rat model, further solidifying its
Correspondence to: Dr Frederick L. Taylor, Department of Urology,
role as a central modulator of collagen deposition in PD
Rush University Medical Center, 1653 W. Congress Parkway,
Suite 348 Professional Building, Chicago, IL 60612, USA.
A second group of profibrotic enzymes includes the
fibrin/plasminogen activator inhibitor 1 (PAI-1) system.
Plasmin breaks down the extracellular matrix both directly
*Laurence A. Levine is a consultant with Pfizer, Lilly, American
and indirectly by activating matrix metalloproteinases
Medical Systems, Auxilium and Coloplast, a speaker for Pfizer,Lilly, Coloplast and Auxilium, and an investigator with fsPhysioMed
(MMP) to break down collagen. PAI-1 in turn inhibits
MMP as well as plasminogen activator, which stimulates
Tel: +86-21-5492-2824; Fax: +86-21-5492-2825; Shanghai, China
2008, Asian Journal of Andrology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences. All rights reserved. Non-surgical therapy of Peyronie’s disease
plasmin . Fibrin itself has been recognized as an in-
groups, including MMP-2, MMP-9, and thymosins TM10
ducer of PD [6, 7], and has been used in causing PD in
an animal model . It has been documented that levelsof TGF-1 and PAI-1 are increased in fibrin-induced PD
3 Non-surgical therapy for PD
The major identified anti-fibrotic enzymes are the
Since the first description of PD in the published
MMP. Although many different MMP have been identified,
literature, clinicians have been searching for medical
there are a few that appear more relevant in PD research.
therapy options with few showing reliable results. Con-
Collagen I breakdown is mediated by MMP 1 and 13, while
sistent success with medical therapies continues to evade
for collagen III MMP 1, 3, 10 and 13 are most active.
the practicing urologist, although current research into
The only MMP produced by mammals that have been
the molecular pathophysiology of PD might one day lead
shown to substantially degrade Collagen 1 and III are types
to medical cure. Several nonsurgical options, however,
1, 8 and 13 . In addition, current studies are currently
are currently available which may stabilize or reduce de-
underway examining the possibility of fibrosis regression,
formity and improve sexual function. The evaluation of
through the induction of the nitric-oxide synthase (NOS)
their efficacy has been compromised by small size of
published clinical trials and most without any placebo
Recent work has further elucidated the molecular
control. Data outcomes are difficult to interpret without
biology of PD, and has unearthed potential targets for
a validated questionnaire, and is complicated by the fact
molecular-based therapies. Ryu et al.  evaluated the
that there is a spontaneous improvement rate of 5%–
efficacy of a TGF-1 inhibitor in the treatment of induced
12% [13–16]. The nonsurgical options for treatment of
PD in a rat model. The rats were injected with TGF-1
the pain and curvature of PD, including oral, topical,
into the tunica albuginea, inducing a PD-like state. The
intralesional, external energy and combination therapies,
rats were randomized into four groups: the control, PD
are presented in the following subsections (Table 1).
group without treatment, PD with saline injections, andPD with IN-1130 injections. IN-1130 is a small mo-
3.1 Oral therapies
lecule that inhibits activin receptor-like kinase 5 (ALK5),which is a receptor for TGF-1. The rats with PD that
were treated with IN-1130 showed significant reduction
Vitamin E was the first oral therapy described for the
in curvature and fibrosis when compared to those re-
treatment of PD . Vitamin E is a fat soluble vitamin
ceiving either no injections or saline injections. The treat-
that is metabolized in the liver, excreted in bile, and is
ment group recorded post-treatment curvatures of 9.1°
postulated to have antioxidant properties in humans. Oxi-
vs. 23.0° and 32.6° for the no injection and saline injec-
dative stress and the production of reactive oxygen spe-
cies (ROS) is known to be increased during the acute
Del Carlo et al.  investigated the role of MMP
and proliferative phases of wound healing, as it is neu-
and tissue inhibitors of matrix metalloproteinases (TIMP)
trophils and macrophages that produce these ROS spe-
in the pathogenesis of PD using harvested plaque from
cies , and the inflammatory phase of wound healing
human PD patients. PD tissue samples were found to
has been shown to be prolonged in Peyronie’s patients
have reduced or absent levels of MMP 1, 8 and 13 when
. Therefore, a biochemical mechanism does exist
compared to patient-matched perilesional tunica. PD fi-
for Vitamin E use. Gelbard et al.  compared vitamin
broblasts were then cultured with soluble MMP and TIMP
E therapy to the natural history of PD in 86 patients; no
after treatment with either TGF-1 or IL-1. They found
significant differences were found between the two
that IL-1 stimulation increased the production of MMP
groups in terms of curvature, pain, or the ability to have
1, 2, 8, 9, 10 and 13 in PD fibroblasts, while TGF-1
intercourse. In 1983, Pryor et al.  conducted a
increased the production of only MMP 10, and decreased
double-blind, placebo-controlled crossover study evalu-
the production of MMP-13, but markedly increased the
ating vitamin E for the treatment of PD in 40 patients.
production of all TIMP. These findings suggest that PD
No significant improvements were noted in plaque size
fibroblasts may be manipulated to encourage scar re-
or penile curvature. The authors do not recommend vi-
modeling in the final phase of wound healing.
tamin E for the treatment of PD as there is no meaning-
It is reasonable to consider that a genetic predisposi-
ful evidence of benefit in placebo-controlled trials.
tion towards impaired wound healing and PD exists. Qianet al.  compared gene expression profiles in samples
taken from PD tunica albuginea plaques, Dupuytren’s
Colchicine is an antigout agent that inhibits fibrosis
contractures and normal palmar fascia, and found several
and collagen deposition primarily by inhibiting neutrophil
gene family similarities between the PD and Dupuytren’s
microtubules . Colchicine has been used both as a
http://www.asiaandro.com; [email protected] Asian J Androl 2008; 10 (1): 79–87
primary oral therapy for PD as well as in combination
competing with estrogen binding sites in target tissues.
with other modalities. Akkus et al.  administered an
In addition, tamoxifen affects the release of TGF from
escalating dose of colchicine in a non-randomized, non-
fibroblasts, and blocks TGF-receptors, thus potentially
placebo controlled fashion to 19 patients with PD over a
reducing fibrogenesis [29, 30]. In 1992, Ralph et al.
3–5-month period . Of these patients, 36% noted a
 investigated tamoxifen in 36 patients with recent
reduction in curvature, and 63% reported an improve-
onset PD (duration less than 4 months) . 80% of
ment in the palpable plaque. Of the patients that were
patients reported a reduction in pain, 35% noted a sub-
experiencing painful erections at the time of treatment
jective reduction in curvature, and 34% reported a de-
initiation, 78% had resolution of this symptom. Kadioglu
crease in plaque size. A follow-up study in 1999 by
et al.  treated 60 patients with PD using 1 mg of colchi-
Teloken et al.  failed to show any statistically sig-
cine twice daily, with a mean follow-up of 11 months .
nificant difference between tamoxifen and a placebo, and
They found significant improvement of pain in 95% of
there was an indidental report of alopecia in the active
men; however, while 30% of patients reported improved
treatment group. We do not recommend the use of
curvature, 22% of patients reported worsened curvature.
Safarinejad performed a randomized, placebo controlledtrial of colchicine in 2004 with 84 men . It was
demonstrated that colchicine was no better than a pla-
Carnitine is a naturally occurring metabolic interme-
cebo in improving pain, curvature angle, or plaque size
diate. Carnitine facilitates the entry of long chain fatty
as measured by ultrasound. Colchicine was not recom-
acids into muscle mitochondria, which are then used as
mended by the authors due to its lack of demonstrated
an energy substrate. Carnitine  is a hypothesized to
efficacy in placebo-controlled trials. The agent is also
inhibit acetyl coenzyme-A, which may help in the repair
associated with gastrointestinal distress, including sig-
of damaged cells. Biagiotti and Cavallini examined the
nificant diarrhea, and rarely aplastic anemia.
use of carnitine for PD in 2001. In their study, 48 menwere divided into two groups to receive either tamoxifen
at 20 mg twice daily for 3 months or acetyl-L-carnitine
Potassium aminobenzoate (Potaba, Glenwood) is a
1 g twice daily for 3 months. Overall, the men taking
member of the vitamin B complex that is believed to in-
carnitine saw greater improvement in curvature, and had
crease the activity of monoamine oxidase in tissues,
statistically significant improvement in pain. In addition,
thereby decreasing local levels of serotonin and, therefore,
the patients taking carnitine reported far fewer side ef-
possibly decreasing fibrogenesis. Potassium amino-
fects as compared to tamoxifen. At this time, more study
benzoate is used for other medical conditions, including
is needed to elucidate the role of carnitine in the treat-
scl er od e r m a , d er m a t om yosi t i s a n d p em p h i g u s.
Zarafonatis and Horrax  first described the use ofpotassium aminobenzoate for the treatment of PD, and a
subsequent European study published in 1978 reported a
L-Arginine is an amino acid that, when catalyzed by
57% improvement rate, with 9% complete resolution in
NOS, combines with oxygen to ultimately form nitric
a pooled cohort of 2 653 patients . This study,
oxide (NO). It is known that inducible NOS (iNOS) is
however, had no control or placebo group. In 1999,
expressed in the fibrotic plaques of PD and suppression
Weidner et al.  published a randomized, placebo con-
of iNOS exacerbates tissue fibrosis . In 2003, Valente
trolled trial of potassium aminobenzoate given 3 g orally
et al.  reported that L-arginine, given daily in the
four times per day for 1 year in 103 men. The only
drinking water of a rat model with TGF-1 induced PD
significant difference found between the two groups was
plaques caused an 80%–95% reduction in plaque size and
plaque size, which in itself was not correlated with a
in the collagen/fibroblast ratio . In addition, L-arginine
decrease in penile curvature. A 2005 follow-up study
was found to be antifibrotic in vitro. This suggests that L-
also by Weidner et al.  suggested that the use of
arginine, as a biochemical precursor of NO, might be ef-
potassium amionobenzoate may protect against progres-
fective in reducing PD plaque size. Further confirmatory
sion in PD plaques. Potassium amin oben zoate is
h uman trials ar e needed befor e th is agent can be
expensive, and has low tolerability because of severe
gastrointestinal side effects. It is also not recommendedby the authors due to a lack of evidence regarding its
Pentoxifylline is a nonspecific PDE inhibitor. Valente
et al.  found that normal human and rat tunica
albuginea, as well as PD plaque tissue, express PDE5A-
Tamoxifen is a nonsteroidal antiestrogen that acts by
3 and PDE4A, B and D. In their in vitro study, PD
Tel: +86-21-5492-2824; Fax: +86-21-5492-2825; Shanghai, China Non-surgical therapy of Peyronie’s disease
Table 1. Nonsurgical therapies for Peyronie’s disease (PD). ESWT, electroshock wave therapy.
Antioxidant that theoretically reverses or stabilizes
Limited side effects, low cost. Efficacy not proven.
pathologic changes in the tunica albuginea.
Inhibits fibrosis and collagen deposition.
Mixed reports of efficacy in non-controlled trials.
Single randomized controlled trial failed to show
benefit. Might cause gastrointestinal disturbances,
Member of the vitamin B complex, thought to
Significant reduction in plaque size, but not
increase the activity of monoamine oxidase,
curvature. Expensive, and difficult to tolerate
thereby decreasing local serotonin levels,
due to gastrointestinal side effects.
which might contribute to fibrogenesis.
Might reduce TGF-release from fibroblasts and
Efficacy not proven. Side effects might include
might block TGF-β receptors, resulting in
Believed to inhibit acetyl coenzyme-A.
Efficacy not proven, and more investigation is
Amino acid substrate in the formation of nitric Improvement in plaque size and collagen/fibroblast
oxide, which is thought to be lacking in PD tissue.
ratio in a rat model. Well tolerated.
Nonspecific phosphodiesterase inhibitor that may
Improvement in plaque size and collagen/fibroblast
reduce collagen levels in PD plaques.
Increases extracellular matrix collagenase secretion
When administered topically the drug does not
through fibroblast inhibition and decreases collagen
appear to penetrate into the tunica albuginea.
and fibronectin synthesis and secretion. Decreases
Anti-inflammatory and cause reduction in collagen
Treatment with steroids is discouraged by the
authors. Effects are unpredictable, and may cause
atrophy and distortion of tissue planes.
Statistically significant improvement in curvature
has been noted in men with mild to moderate disease.
Controlled and noncontrolled trials show promise as
improvements in plaque volume, pain, and curvature
Decreased the rate of proliferation of fibroblasts
Recent encouraging results with reports of improve-
in Peyronie’s plaques in vitro, reduced production
ment in curvature and pain. Dosing regimens and side
of extracellular collagen and increased production
effect profiles yet to be determined. External energy
No statistically significant improvement noted in
resultant plaque lysis, improved vascularity, and
the creation of contralateral scarring.
Effect of verapamil and steroids discussed previously.
Objective improvements of plaque size and curvature
Electric current itself might have some beneficial
have been noted. Adverse effects include erythema at
http://www.asiaandro.com; [email protected] Asian J Androl 2008; 10 (1): 79–87
Table 1 (continued). Nonsurgical therapies for Peyronie’s disease (PD). ESWT, electroshock wave therapy. Combination therapy
Discussed previously. Synergistic effect possible.
Improvements in curvature and plaque size have been
Discussed previously. Synergistic effect possible.
Significant improvement in plaque size compared
Discussed previously. Synergistic effect possible.
Statistically significant subjective improvement in
curvature, plaque size and erectile function in
patients treated with carnitine and intralesional
Penile traction devices
Expansion of contracted tissue might result in the
Early results demonstrate improvement in curvature,
increase in length, and improvement in hinge effect.
Side effects were limited to mild discomfort with
fibroblasts were cultured with pentoxifylline and found
The powerful anti-inflammatory effect of steroids
to have increased cAMP levels and reduced collagen I
made them obvious agents for intralesional therapy of
levels as compared to controls. In addition, pentoxyfilline
PD. In 1954, Bodner et al.  reported improvement
given orally to a TGF-1 induced PD rat model caused a
in 17 patients treated with intralesional hydrocortisone
decrease in PD plaque size and the collagen/fibroblast
and cortisone. In 1975, Winter and Khanna  showed
ratio. Brant et al.  reported a single case report of
no difference between patients treated with dexametha-
successful PD treatment using pentoxifylline alone .
sone injections and the natural history of the disease. In
Further studies are required to definitively examine
1980, Williams and Green  published a prospective
pentoxifylline for the treatment of PD; however, its
study using intralesional triamcinolone. All patients were
known biochemical effect and early animal-model suc-
observed for 1 year after study enrollment; during that
cess make it an attractive option for consideration.
time only 3% of patients reported improvement. Triam-cinolone was administered every 6 weeks for 36 weeks;
33% of patients reported subjective improvement, par-
ticularly in pain and plaque size. Currently, the use of
Interest in topical verapamil for the treatment of PD
intralesional steroids is discouraged because of the side
followed its success as an intra-lesional agent (see below).
effects of local t issue a tr oph y, fibr osis, im mun e
However, investigation has demonstrated that effective
suppression, and lack of objective measures of benefit.
tunica albuginea tissue concentrations of verapamil arenot achievable via topical application . A recent three-
arm trial without placebo demonstrated some benefit with
Collagenase was first studied in vitro by Gelbard et al.
topical verapamil , but this study was significantly
in 1982 . A subsequent clinical trial by that group
compromised . Therefore, the use of verapamil as a
demonstrated subjective improvement in 64% of patients
topical agent for PD is not recommended.
within 4 weeks of treatment . A decade after theirinitial study, they published their findings of a double
blind trial in 49 men . Statistically significant im-
provement in curvature was noted in the collagenase
Tel: +86-21-5492-2824; Fax: +86-21-5492-2825; Shanghai, China Non-surgical therapy of Peyronie’s disease
treated group; however, maximal improvement ranged
dicated in patients with ventral plaques or extensive plaque
from 15° to 20° and was only seen in the patients with
curvatures of less than 30° and plaques of less than 2 cmin length. Larger scale controlled trials of collagenase
Duncan et al.  reported in 1991 that IFNs de-
crease the rate of proliferation of fibroblasts in Peyronie’s
plaques in vitro, reduce the production of extracellular
Verapamil is a calcium channel blocker that has been
collagen, and increase the activity of collagenase. Initial
shown in in vitro studies to inhibit local extracellular matrix
studies performed by Wegner et al. [51, 52] demon-
p r od u ct i on by fi br obl a st s, t o r ed u ce fi br obl a st
strated low rates of improvement, but a high incidence
proliferation, to increase local collagenase activity and to
of side effects, including myalgias and fever. In 1999,
affect the cytokine milieu of fibroblasts [44, 45]. In
Ahuja et al.  reported on 20 men who received
1994, Levine et al.  reported on 14 men who under-
1 × 106 units of IFN-α-2b biweekly for 6 months. Of
went a dose-escalation trial of biweekly intralesional in-
these patients, 100% reported softening of plaque, 90%
jections of verapamil for 6 months. Significant improve-
of men presenting with pain had improvement, and 55%
ment in plaque associated narrowing was noted in all
had a subjective reduction in plaque size. Dang et al.
patients, and curvature was improved in 42%. The first
 administered 2 × 106 units to 21 men biweekly for
randomized single-blind trial of intralesional verapamil was
6 weeks, and found objective curvature improvements
published in 1998 . Significant improvement were
in 67%, and improvement in pain in 80%. Seventy-one
noted in terms of erection quality and plaque volume. A
per cen t of patien ts r ep or ted impr ovemen t in ED
non-statistical trend towards improvement in curvature
symptoms. In 2006, Hellstrom et al.  reported on a
was also noted. As a follow-up, Levine and Estrada 
placebo controlled, multicenter trial of 117 patients who
reported on 156 men enrolled in a prospective non-ran-
underwent biweekly injections of 5 × 106 units for a to-
domized trial of PD men with a mean follow-up of
tal of 12 weeks. Average curvature in the treatment group
30.4 months. A local penile block was performed with
improved 13°, versus 4° in the placebo arm, and 27% of
10–20 mL 0.5% bupivicaine, followed by injection of
patients in the treatment group had measured improve-
10 mg verapamil diluted in 6 mL sterile normal saline (total
ment versus 9% of the saline group. Pain resolution was
volume 10 mL) into the Peyronie’s plaque using 1–5 skin
noted in 67% of the treatment patients versus 28% for the
punctures, but with multiple passes through the plaque.
placebo. IFN therapy requires investigation to further define
The goal is to leave the drug in the needle tracks, not to
efficacy, dosing regimens, and side effect profiles.
tear or disrupt the plaque. Injections were administeredevery 2 weeks for a total of 12 injections. Of patients
with pain, 84% achieved complete resolution, 62% were
3.4.1 Penile electroshock wave therapy (ESWT)
found on objective measurement to have improved cur-
Local penile ESWT has been suggested to be of be-
vature ranging from 5–75° (mean 30°), and only 8% of
nefit for the treatment of PD. Various hypotheses about
patients had measured worsening of curvature. More
its mechanism of action exist, including direct damage
recently, Bennett et al.  administered six intralesional
to the plaque resulting in an inflammatory reaction with
injections (10 mg in 5 mL) every 2 weeks to 94 con-
increased macrophage reaction leading to plaque lysis,
secutive patients with PD . Follow-up was at
improved vascularity resulting in plaque resorption, and
5.2 months after completion of the 6th injection. Of
the creation of contralateral scarring of the penis result-
patients, 18% (n = 17) were found to have improved
ing in “false” straightening . Hauck et al.  ran-
curvatures (average improvement 12°), 60% (n = 56)
domized 43 men to ESWT or oral placebo for 6 months
had stable curvature, and 22% (n = 21) had increased
. No significant effect was noted in ter ms of
curvature (average increase 22°). All patients with pre-
curvature, plaque size, or subjective improvement in se-
treatment penile pain had improvement at follow-up. The
xual function or rigidity. More recent work from a Ger-
authors suggest that these data support intralesional
man group randomized 102 men to ESWT or to receive
verapamil for the stabilization of PD. It might be that six
placebo shocks [58, 59]. There was no statistically sig-
injections provides stabilization but is insufficient to ac-
nificant difference found between the groups for plaque
complish reduction of curvature. Currently, we recom-
size, improvement of deformity, or sexual function post-
mend a trial of six injections with each injection occur-
treatment. ESWT is currently not recommended as
ring every 2 weeks. If no improvement is noted by the
patient, the therapy may be terminated, the verapamil dosecan be increased to 20 mg, or interferon (IFN) injec-
tions may be offered. We consider verapamil contrain-
Iontophoresis involves the transport of ions through
http://www.asiaandro.com; [email protected] Asian J Androl 2008; 10 (1): 79–87
tissue by means of an electric current. Several studies
receive intralesional verapamil plus oral carnitine or
have investigated th e efficacy of topically applied
intralesional verapamil plus oral tamoxifen. Statistically
verapamil with or without dexamethasone with enhanced
significant subjective improvements in curvature, plaque
penetration using iontophoresis [60–63]. In 2002, Levine
size and erectile function were found in the carnitine
et al.  confirmed that verapamil was found within
group. No difference in improvement of pain was noted
the exposed tunica albuginea by examining surgically re-
trieved tunica albuginea from patients after a single intra-operative exposure during plaque incision and grafting
surgery. Di Stasi et al.  recently reported on a
The use of tissue expanders has long been a main-
prospective, randomized study of 96 patients treated with
stay of treatment in the orthopedic, oral-maxillofacial and
5 mg verapamil plus 8 mg dexamethasone using ionto-
plastic surgical fields. It is well-documented that gradual
phoresis versus 2% lidocaine delivered electromotively.
expansion of tissue results in the formation of new bone
Of patients in the verapamil/dexamethasone group, 43%
and connective tissue. Initial work has been done to
noted objective improvement in plaque size and curvature;
evaluate th e efficacy of a pen ile exten der device
no changes were noted in the lidocaine group. In 2005,
(fsPhysioMed; FastSize LLC, Aliso Viejo, CA, USA)) for
Greenfield et al.  reported on the use of 10 mg
the treatment of PD. A pilot study at our institution of 10
verapamil versus saline iontophoresis. Patients were as-
patients found that daily application of the fsPhysioMed
sessed using papavarine-induced erections prior to and
device for 2–8 h per day for 6 months resulted in a 33%
1 month after treatment. Of patients in the verapamil
measured improvement in curvature (ranging from a 10°
group, 65% demonstrated improvement in curvature,
to 45° improvement and resulting in an improvement in
versus 58% in the saline group. Mean curvature im-
average curvature from 51° to 34°), an increase in flac-
provement was 9.1° in the treatment group versus 7.6°
cid stretched penile length ranging from 0.5–2.0 cm, and
in the saline group, which is not as robust as intralesional
an improvement in hinge effect in all those with advanced
verapamil injections. The authors suggested that the elec-
narrowing or indentation. No patients noted recurrence
tric current itself might have some beneficial effect on
or worsening of curvature during 6 months of follow-
wound healing, which is known and supported in the
up, and there was no incidence of local skin changes,
dermatologic literature . Further investigation into
ulceration, loss of sensation, or worsening of curvature.
Long term and larger studies are indicated. 4 Conclusion
A placebo controlled study by Preito Castro et al.
Our current practice favors a multi-modal approach
 randomized 45 patients to receive vitamin E and
for non-surgical therapy for PD. All patients are pre-
colchicine or ibuprofen. Statistically significant improve-
scribed 400 mg pentoxifylline orally three times a day,
ments in curvature and plaque size were noted in the
with L-Arginine 1 000 mg twice a day. Patients are en-
group treated with vitamin E and colchicine as compared
couraged to use the fsPhysioMed device 2–8 h per day
to the group receiving ibuprofen. Patients in the vitamin
for 6 months, and are offered intralesional verapamil in-
E and colchicine arm reported a greater decrease in pain,
jections as a means to improve curvature and, if present,
although this did not reach statistical significance.
pain. As a result of increased interest in this disorder aswell as more sophisticated basic science and clinical
3.5.2 ESWT with per perilesional verapamil injection
research, effective and reliable non-surgical treatments
In 1999, Mirone et al.  prospectively examined
will hopefully emerge. In the meantime, there are a num-
two groups of PD patients; one group was treated with
ber of non-surgical treatment options that offer some
ESWT, while the other received ESWT and perilesional
benefit with respect to disease stabilization as well as
verapamil injections. A 52% improvement in plaque size
reduction of deformity and improved sexual function.
by ultrasound was noted in the ESWT-only group com-pared to 19% for the combination therapy. A follow-up
study by the same investigators involving 481 patients
De La Peyronie F. Sur quelques obstaclesqui sópposent à
demonstrated a 49% improvement in plaque size among
l’éjaculation nautrelle de la semence. Mem Acad Royale Chir
those treated with combination therapy .
El-Sakka AI, Hassoba HM, Chui RM, Bhatnagar RS, Dahiya R,
3.5.3 Intralesional verapamil with oral carnitine or
Lue TF. An animal model of Peyronie’s like condition associ-ated with an increase of transforming growth factor β mRNA and
protein expression. J Urol 1997; 158: 2284–90.
In 2002, Cavallini et al.  randomized 60 men to
El-Sakka AI, Hassoba HM, Pillarisetty RJ, Dahiya R, Lue TF. Tel: +86-21-5492-2824; Fax: +86-21-5492-2825; Shanghai, China Non-surgical therapy of Peyronie’s disease
Peyronie’s disease is associated with an increase in transforming
Zarafonetis CJ, Horrax TM. Treatment of Peyronie’s disease
growth factor-beta protein expression. J Urol 1997; 158: 1391–4.
with potassium para-aminobenzoate (potaba). J Urol 1959; 81:
Bivalacqua TJ, Champion HC, Leungwattanakij S, Yang DY,
Hyun JS, Abdel-Mageed AB, et al. Evaluation of nitric oxide
Hasche-Klunder R. Treatment of Peyronie’s disease with para-
synthase and arginase in the induction of a Peyronie’s like con-
aminobenzoacidic potassium (Potoba) (author’s translation).
dition in the rat. J Androl 2001; 22: 497–506.
Kucharewicz I, Kowal K, Buczko W, Bodzenta-Lukaszyk A. The
Weidner W, Schroeder-Printzen I, Rudnick J. Randomized pro-
plasmin system in airway remodeling. Thromb Res 2003; 112: 1–7.
spective placebo-controlled therapy of Peyronie’s disease (IPP)
Van de Water L. Mechanisms by which fibrin and fibronectin
with Potaba (aminobenzoate potassium). J Urol 1999; 6: 205.
appear in healing wounds: implications for Peyronie’s disease. J
Weidner W, Hauck EW, Schnitker J. Peyronie’s Disease Study Group
of Andrological Group of German Urologists. Potassium
Davila HH, Magee TR, Zuniga FI, Rajfer J, Gonzalez-Cadavid
paraaminobenzoate (Potaba) in the treatment of Peyronie’s
NF. Peyronie’s disease is associated with an increase of plasmi-
disease: a prospective, placebo-controlled, randomized study. Eur
nogen activator inhibitor-1 in fibrotic plaque. Urology 2005;
Ralph DJ, Brooks MD, Bottazzo GF, Pryor JP. The treatment of
Davila HH, Ferrini MG, Rajfer J, Gonzalez-Cadavid NF. Fibrin as
Peyronie’s disease with tamoxifen. Br J Urol 1992; 70: 648–51.
an inducer of fibrosis in the tunica albuginea of the rat: a new
Colletta AA, Wakefield LM, Howell FV, van Roozendaal KE,
animal model of Peyronie’s disease. BJU Int 2003; 91: 830–8.
Danielpour D, Ebbs SR, et al. Anti-oestrogens induce the secre-
Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem
tion of active transforming growth factor beta from human fetal
fibroblasts. Br J Cancer 1990; 62: 405–9.
Ryu JK, Piao S, Shin HY, Zhang L, Jin H, Han JY, et al. IN-
Teloken C, Rhoden EL, Grazziotin TM, Ros CT, Sogari PR, Souto
1130, A novel transforming growth factory type 1 receptor
CA. Tamoxifen versus placebo in the treatment of Peyronie’s
kinase (ALK 5) inhibitor regresses fibrotic plaque and corrects
disease. J Urol 1999; 162: 2003–5.
penile curvature in a rat model of Peyronie’s Disease. Annual
Biagiotti G, Cavallini G. Acetyl-L-carnitine vs tamoxifen in the
Meeting of the American Urological Association, 2007, May
oral therapy of Peyronie’s disease: a preliminary report. BJU
19–24, 2007, Anaheim, California, USA. Abstract 749.
Del Carlo M, Levine LA, Cole AA. Differential regulation of
Valente EG, Vernet D, Ferrini MG, Qian A, Rajfer J, Gonzalez-
matrix metalloproteinases (MMP) and tissue inhibitors of ma-
Cadavid NF. L-Arginine and phosphodiesterase (PDE) inhibitors
trix metalloproteinases (TIMPs) by interleukin-1 β (IL-1 β) and
counteract fibrosis in the Peyronie’s fibrotic plaque and related
transforming growth factor β (TGF-β in Peyronie’s fibroblasts.
fibroblast cultures. Nitric Oxide 2003; 9: 229–44.
Annual Meeting of the American Urological Association, 2007,
Brant WO, Dean RC, Lue TF. Treatment of Peyronie’s disease
May 19–24, 2007, Anaheim, California, USA. J Urol 2007; 177
with oral pentoxifylline. Nat Clin Pract Urol 2006; 3: 111–5.
Martin DJ, Badwan K, Parker M, Mulhall JP. Transdermal appli-
Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF. Comparison
cation of verapamil gel to the penile shaft fails to infiltrate the
of gene expression profiles between Peyronie’s disease and
tunica albuginea. J Urol 2002; 168: 2483–5.
Dupuytren’s contracture. Urology 2004; 64: 399–404.
Fitch WP 3rd, Easterling WJ, Talbert RL, Bordovsky MJ, Mosier
Deveci S, Hopps CV, O’Brien K, Parker M, Guhring P, Mulhall
M. Topical verapamil HCl, topical trifluoperazine, and topical
JP. Defining the clinical characteristics of Peyronie’s disease in
magnesium sulfate for the treatment of Peyronie’s disease – a
young men. J Sex Med 2007; 4: 485–90.
placebo-controlled pilot study. J Sex Med 2007; 4: 477–84.
Williams JL, Thomas GG. The natural history of Peyronie’s
Levine LA. Comment on: Topical verpamil HC l, topical
trfluoperazine, and topical magnesium sulfate for the treatment
Gelbard MK, Dorey F, James K. The natural history of Peyronie’s
of Peyronie’s disease – a placebo-controlled pilot study. J Sex
disease. J Urol 1990; 144: 1376–9.
Deveci S, Hopps CV, O’Brien K, Parker M, Guhring P, Mulhall
Bodner H, Howard AH, Kaplan JH. Peyronie’s disease: cortisone-
JP. A retrospective review of 307 men with Peyronie’s disease.
hyaluronidase-hydrocortisone therapy. J Urol 1954; 400–3.
Winter CC, Khanna R. Peyronie’s disease: results with dermo-
Scott WW, Scardino PL. A new concept in the treatment of
jet injection of dexamethasone. J Urol 1975; 114: 898–900.
Peyronie’s disease. South Med J 1948; 41: 173–7.
Williams G, Green NA. The non-surgical treatment of Peyronie’s
Sikka SC, Hellstrom WJ. Role of oxidative stress and antioxidants
disease. Br J Urol 1980; 52: 392–5.
in Peyronie’s disease. Int J Impot Res 2002; 14: 353–60.
Gelbard MK, Walsh R, Kaufman JJ. Collagenase for Peyronie’s
Gholami SS, Gonzalez-Cadavid NF, Lin CS, Rajfer J, Lue TF.
disease experimental studies. Urol Res 1982; 10: 135–40.
Peyronie’s disease: a review. J Urol 2002; 169: 1234–41.
Gelbard MK, Linkner A, Kaufman JJ. The use of collagenase in the
Pryor JP, Farell CF. Controlled clinical trial of vitamin E in
treatment of Peyronie’s disease. J Urol 1985; 134: 280–3.
Peyronie’s Disease. Prog Reprod Biol 1983; 9: 41–5.
Gelbard MK, James K, Riach P, Dorey F. Collagenase vs. placebo
Furst DE, Munster T. Nonsteroidal anti-inflammatory drugs,
in the treatment of Peyronie’s disease: a double blind study. J
disease-modifying antirheumatic drugs, nonopioid analgesics &
drugs used in gout. In: Basic and Clinical Pharmacology. Bertram
Roth M, Eickelberg O, Kohler E, Erne P, Block LH. Ca2+ chan-
G, editor. Katzung Lange: New York; 2001.
nel blockers modulate metabolism of collagens within the extra-
Akkus E, Carrier S, Rehman J, Breza J, Kadioglu A, Lue TF. Is
cellular matrix. Proc Natl Acad Sci U S A 1996; 93: 5478–82.
colchicine effective in Peyronie’s disease? A pilot study. Uro-
Mulhall JP, Anderson MS, Lubrano T, Shankey TV. Peyronie’s
disease cell culture models: phenotypic, genotypic and functional
Kadioglu A, Tefekli A, Koksal T, Usta M, Erol H. Treatment of
analyses. Int J Impot Res 2002; 14: 397–405.
Peyronie’s disease with oral colchicine: long term results and
Levine LA, Merrick PF, Lee RC. Intralesional verapamil injec-
predictive parameters of successful outcome. Int J Impot Res
tion for the treatment of Peyronie’s disease. J Urol 1994; 151:
Safarinejad MR. Therapeutic effects of colchicine in the ma-
Rehman J, Benet A, Melman A. Use of intralesional verapamil
nagement of Peyronie’s disease: a randomized double-blind, pla-
to dissolve Peyronie’s disease plaque: a long term single-blind
cebo-controlled study. Int J Impot Res 2004; 16: 238–43. http://www.asiaandro.com; [email protected] Asian J Androl 2008; 10 (1): 79–87
Levine LA, Estrada CR. Intralesional verapamil for the treat-
extracorporeal shock wave therapy on plaque size and sexual
ment of Peyronie’s disease: a review. Int J Impot Res 2002; 14:
function in patients with Peyronie’s Disease – results of a
prospective, randomized, placebo-controlled study. Annual Meet-
Bennett NE, Guhring, P, Mulhall JP. Intralesional verapamil
ing of the American Urological Association, 2007, May 19–24,
prevents the progression of Peyronie’s Disease. Urology 2007;
2007, Anaheim, California, USA. J Urol 2007; 177(4 Suppl):
Duncan MR, Berman B, Nseyo UO. Regulation of the prolifera-
Riedl CR, Plas E, Engelhard P, Daha K, Pfluger H. Lontophoresis
tion and biosynthetic activities of cultured human Peyronie’s
for treatment of Peyronie’s disease. J Urol 2000; 163: 95–9.
disease fibroblasts by interferons-alpha, -beta and -gamma. Scand
Montorsi F, Salonia A, Guazzoni G, Barbieri L, Colombo R, Brausi
M. Transdermal electromotive multi-drug administration for
Wegner HE, Andreson R, Knipsel HH, Miller K. Treatment of
Peyronie’s disease: preliminary results. J Androl 2000; 21: 85–90.
Peyronie’s disease with local interferon-alpha-2b. Eur Urol 1995;
Di Stasi SM, Giannantoni A, Capelli G, Jannini EA, Virgili G,
Storti L, et al. Transdermal electromotive administration of
Wegner HE, Andresen R, Knipsel HH, Miller K. Local inter-
verapamil and dexamethasone for Peyronie’s disease. BJU Int
feron-alpha 2b is not an effective treatment in early-stage
Peyronie’s disease. Eur Urol 1997; 32: 190–3.
Di Stasi SM, Giannantoni A, Stephen RL, Capelli G, Glurioli A,
Ahuja S, Bivalacqua TJ, Case J, Vincent M, Sikka SC, Hellstrom
Jannini EA, et al. A prospective, randomized study using transdermal
WJ. A pilot study demonstrating clinical benefit from intralesional
electromotive administration of verapamil and dexamethasone
interferon alpha 2B in the treatment of Peyronie’s disease. J
for Peyronie’s disease. J Urol 2004; 171: 1605–8.
Levine LA, Estrada CR, Show W, Cole A. Tunica albuginea tissue
Dang G, Matern R, Bivalacqua TJ, Sikka S, Hellstrom WJ.
analysis after electromotive drug administration. J Urol 2003;
Intralesional interferon-alpha-2B injections for the treatment
of Peyronie’s disease. South Med J 2004; 97: 42–6.
Greenfield JM, Shah SJ, Levine LA. Verapamil versus saline in
Hellstrom WJ, Kendirci M, Matern R, Cockerham Y, Myers L,
electromotive drug administration (EDMA) for Peyronie’s disease:
Sikka SC, et al. Single-blind, multicenter placebo-controlled par-
a double blind, placebo controlled trial. J Urol 2007; 177: 972–5.
allel study to asses the safety and efficacy of intralesional inter-
Ojingwa JC, Isseroff RR. Electrical stimulation of wound healing.
feron alpha-2B for minimally invasive treatment for Peyronie’s
J Invest Dermatol 2003; 121: 1–12.
Preito Castro RM, Leva Vallejo ME, Regueiro Lopez JC, Anglada
Levine LA. Review of current nonsurgical management of
Curado FJ, Alvarez Kindelan J, Requena Tapia MJ. Combined
Peyronie’s disease. Int J Impot Res 2003; 15: S113–20.
treatment with vitamin E and colchicines in the early stages of
Hauck EW, Altinkilic BM, Ludwig M, Ludecke G, Schroeder-
Peyronie’s disease. BJU Int 2003; 91: 522–4.
Printzen I, Arens C, et al. Extracorporeal shock wave therapy in
Mirone V, Palmieri A, Granata AM, Piscopo A, Verze P, Ranavolo
the treatment of Peyronie’s disease. First results of a case-
R. Ultrasound-guided ESWT in Peyronie’s disease plaques. Arch
controlled approach. Eur Urol 2000; 38: 663–70.
Hatzichristodoulou G, Meisner C, Liske P, Stenzl A, Lahm S.
Mirone V, Imbimbo C, Palmieri A, Fusco F. Our experience on
Efficacy of extracorporeal shock wave therapy (ESWT) in pa-
the association of a new physical and medical therapy in patients
tients with Peyronie’s disease (PD)–first results of a prospective,
suffering from induration penis plastica. Eur Urol 1999; 36:
randomized, placebo-controlled, single-blind study. American Uro-
logical Association 2006 Annual Meeting. May 20–25, 2006,
Cavallini G, Biagiotti G, Koverech A, Vitali G. Oral propionyl-l-
Atlanta, Georgia, USA. J Urol 2006; 175 (4 Suppl): Abstract 993.
carnitine and intraplaque verapamil in the therapy of advanced
Hatzichristodoulou G, Meisner C, Stenzyl A, Lahm S. Efficacy of
and resistant Peyronie’s disease. BJU Int 2002; 89: 895–900. Tel: +86-21-5492-2824; Fax: +86-21-5492-2825; Shanghai, China
Physikalische Chemie auf der Baustelle aude gibt Einblicke in den Alltag einer Baustelle. Hierbei k¨chemische Grundkenntnisse von Nutzen sein, wie Sie sie im ersten Semester (gelegentlich unter Baul¨ 1. Feinstaubsedimentation (10P) Auf der Baustelle entsteht viel Feinstaub. Bestimmen Sie die station¨ornchens (Dichte 7.85 g/cm3) mit einem Durchmesser von 0.0015at 17.1 · 10 − 6 Pa s b
Content Recommendations for the Sideline Bag Author: William A. Moreau, D.C., DACBSP Estherville, Iowa 51334-2409 [email protected] Iowa Chiropractic Society Article - FEB 2003 Drs. Bart Green and Hal Rosenberg recently published an article entitled Contents for Chiropractors Emergency Sideline Bags in the November / December issue of the Journal of Manipulation and Physiological T