The management of peyronie's disease: evidencebased 2010 guidelines
The Management of Peyronie’s Disease: Evidence-based
David Ralph, MD,* Nestor Gonzalez-Cadavid, PhD,† Vincenzo Mirone, MD,‡ Sava Perovic, MD,§Michael Sohn, MD,¶ Mustafa Usta, MD,** and Laurence Levine, MD††
*Institute of Urology, London UK; †Department Urology, UCLA, CA, USA; ‡University of Naples “Federico II”, Naples,Italy; §University of Belgrade, Belgrade, Serbia; ¶University Aachen, Germany; **Akdeniz University School of Medicine,Antalya, Turkey; ††Rush Medical College, Chicago, IL, USA
A B S T R A C T
The ﬁeld of Peyronie’s disease is evolving and there is need for a state-of-the-art information in this area.Aim.
To develop an evidence-based state-of-the-art consensus report on the management of Peyronie’s disease.Methods.
To provide state-of-the-art knowledge regarding the prevalence, etiology, medical and surgical manage-
ment of Peyronie’s Disease, representing the opinion of leading experts developed in a consensus process over a
2-year period.Main Outcome Measures.
Expert opinion was based on grading of evidence-based medical literature, widespread
internal committee discussion, public presentation, and debate.Conclusions.
The real etiology of Peyronie’s disease and the mechanisms of formation of the plaque still remain
obscure. Although conservative management is obtaining a progressively larger consensus among the experts,
surgical correction still remains the mainstay treatment for this condition. Ralph D, Gonzalez-Cadavid N, Mirone
V, Perovic S, Sohn M, Usta M, and Levine L. The management of Peyronie’s disease: Evidence-based 2010
guidelines. J Sex Med 2010;7:2359–2374.
Peyronie’s Disease; Guidelines; Surgery; Pathology
the patient and partner may be signiﬁcantlyaffected, with an increased risk of depression, low
P eyronie’s disease (PD) is currently consid- self-esteem, and relationship difﬁculties being
ered a wound healing disorder that presents
common [1–3]. Overall, approximately 30% of
with a ﬁbrous inelastic scar of the tunica albug-
patients will have diabetes, which has been found
inea that is currently believed to occur in the
to be associated with advanced curvatures and
vasculogenic ED [4,5]. Two thirds of patients
trauma to the penis. It is characterized by the
with PD are likely to have risk factors for arterial
development of a palpable scar, which in the
disease and therefore worsening long-term erec-
erect state causes a variety of deformities, includ-
tile function . PD is a progressive disorder
ing curvature, shortening, narrowing, and hinge
with up to 48% of men having disease progres-
effect. In the early phase there is often an inﬂam-
sion if left untreated . In most cases, PD may
matory component that causes pain. PD is also
be divided into an acute inﬂammatory phase and
frequently associated with erectile dysfunction
a chronic phase. During the former, there may be
(ED), and a variety of other comorbid disorders,
penile pain and curvature progression although
including diabetes, hypertension, dyslipidemia,
the pain typically resolves spontaneously within
and low testosterone. The quality of life of both
6–18 months from onset in most patients .
2010 International Society for Sexual Medicine
may cause penile shortening with or without
PD—OVERVIEW GRADE A
a penile deformity . The consistency of the
PD is a physically and psychologically devas-
plaque, be it soft, tender, calciﬁed, or ossiﬁed
tating problem manifest by a fibrous inelastic
should be noted as this may act as a guide to
scar of the tunica albuginea, which results in
management. Calciﬁcation may occur at initial
a penile deformity (e.g., bending, narrowing,
presentation or develop over time. It appears
hinging, shortening), as well as painful erec-
that calciﬁcation is not a manifestation of a more
tions, all of which may lead to difficulty with
mature plaque as previously thought. Rather it
intromission. There are relatively few high-
may represent a different genetic subtype of PD
level evidence-based therapeutic studies.
An assessment of the curvature on erection is
PREVALENCE OF PD GRADE B
best made by an intracavernosal injection of a
Multiple demographic studies have been
vasoactive agent; a home photograph or a vacuum
performed world-wide indicating a preva-
assisted erection test can be also useful in the diag-
lence rate of 3–9% in adult men. Therefore,
nosis . This also allows complex curvatures to
PD is not a rare disorder.
be assessed and will aid in the decision for the typeof treatment best suited to the individual. The
NATURAL HISTORY GRADE C
severe emotional distress that occurs is, in part, a
The natural history of PD has been evaluated
result of the deformity, but mainly because of the
in only a few level 2 and 3 studies indicating
penile shortening that occurs in almost all patients
that spontaneous deformity resolution is not
with up to 50% of them being clinically depressed.
common and remains less than 13%.
It is imperative therefore that the stretched penilelength is measured preoperatively so that thepatients realize that the length loss postoperatively
is mainly a result of the disease itself and not to the
The diagnosis of PD is usually apparent from the
surgery [13–15]. ED associated with PD has been
patient history and penile examination. The main
reported in up to 58% of men [2,5]. It is not
points to gather from the history are whether the
uncommon for unsuspected PD to be diagnosed at
disease is still active, the nature of the curvature
the time of investigation of their ED [16,17]. Since
and the presence of ED. Patients with short
ED is a common ﬁnding in patients with PD .
disease duration (<12 months), penile pain, or a
A detailed history of any arterial risk factors for
recent change in penile deformity are still likely to
ED should be noted and an assessment of erectile
have active inﬂammatory disease and therefore are
function best made by the validated International
not surgical candidates and would be more likely
Index of Erectile Function-5 questionnaire . A
to beneﬁt from medical therapy. Penile pain may
PD-speciﬁc questionnaire is in development and
be persistent in the inﬂammatory stage of the
should aid in the assessment of the man with PD
disease but is usually only present during erection.
and may prove useful in evaluating quality of like-
The pain is not usually severe in nature but may
related changes following treatment.
interfere with sexual function although spontane-ous improvement usually occurs as the inﬂamma-
tion settles within 6 months and almost all men
Ultrasound is used to identify the site and con-
will experience pain resolution by 18 months (94%
sistency of the plaque and is a useful tool in the
of 246 men treated conservatively) [6–9].
clinical trial setting to assess penile vascular blood-
All the patients have either a well deﬁned plaque
ﬂow parameters. It can also determine the extent
or an area of induration that is palpable on phy-
of plaque calciﬁcation as those men with extensive
sical examination, even though patients may be
calciﬁcation have historically been noted to not
unaware of it . The plaque is located on the
respond well to nonsurgical therapies. Extensive
dorsal surface of the penis in two thirds of patients
calciﬁcation appears to be a primary indication for
with a corresponding dorsal penile deformity .
surgical correction as these plaques do not respond
Lateral and ventral sited plaques are not as
to medical therapy. It is a minimally-invasive tech-
common but result in more coital difﬁculties as
nique that is more accurate than X-ray, CT scan,
there is a greater deviation from the natural coital
or MRI . A vascular assessment should be per-
angle. Multiple plaques located on opposite sides
formed in all patients with ED as well as those
of the penis or plaques appearing in the septum
undergoing surgery and is best done using duplex
ultrasound . The results of this investigation
affecting 39% of PD patients vs. only 1.2% in the
can often show vascular disease in patients who
report normal potency which may inﬂuence the
Epidemiological studies showed that PD is
signiﬁcantly associated with diabetes [3,5,31,32,34,37,41–43]. Some of these reports provideddata supporting a signiﬁcant association of PDwith obesity [34,38,43], hypertension [3,5,36,41],
hyperlipidemia [3,5,33,34,37,38], smoking [32,34,
37,38,42,43], and pelvic surgery .
There is no international standard for
evaluation or reporting on treatment out-
comes for PD. A detailed history should be
COMMON COMORBIDITIES GRADE D
obtained focusing on onset, duration, pain,
Multiple comorbidities have been identi-
fied, including ED, hypertension, diabetes
mellitus, hyperlipidenia, low testosterone,
and Dupuytren’s disease. It remains unclear
ASSESSMENT GRADE D
whether any of these contribute to the
Suggested objective measures include: mea-
development of PD.
suring stretched penile length, and describ-
ing plaque location (dorsal, ventral, septal,
proximal, distal, etc.)
Etiology and Histopathology
A widely accepted hypothesis on the etiology
CLINICAL DIAGNOSIS—PLAQUE SIZE
of the PD plaque is that it originates from trauma
or microtrauma to the erect penis [44–55] in
Plaque measurement is inaccurate by any
patients with genetic predisposition to form
modality, as well as operator dependent and
localized ﬁbrosis as a response to trauma.
therefore is not a reliable assessment for
[56–62]. The main pathological process is tissue
ﬁbrosis with disorganization of elastic ﬁbers,combined in most cases with ﬁbrin accumulation
and different degrees of inﬂammation [48,50,
ULTRASOUND GRADE D
63–75]. Consequently, spontaneous regression is
Dynamic duplex ultrasound provides assess-
ment of plaque calcification, vascular flow
Recent studies on an animal model suggest
parameters, and objective measures of defor-
that transforming growth factor beta (TGFb1)
mity. It is a useful but not necessary test.
74,81–83,87–95] play an important role in the for-mation of PD plaques. TGFb1 is also found in the
Epidemiology: Prevalence and Comorbidities
human PD plaque and is the main proﬁbrotic
Recent studies suggest a prevalence of PD in the
factor in multiple tissues , while myoﬁbro-
population that can reach up to 9% [22–33], much
blasts are a common feature in most tissue ﬁbrosis
and in abnormal wound healing , and their
The mean age of onset of the condition in these
persistence by the inhibition of programmed cell
studies was 55–60 years, and penile curvature was
death leads to scar formation . Moreover, the
present in over 80% of patients whereas pain-
tunica albuginea is known to contain pluripotent
ful erection was reported by over half of them
stem cells that are potentially able to differentiate
into myoﬁbroblasts, smooth muscle cells, and
History of a penile trauma has been reported by
osteoblasts, and in a paracrine fashion to modulate
the differentiation of a multipotent cell line into
Some studies have revealed a signiﬁcant asso-
osteoblasts and myoﬁbroblasts [11,97–109]. The
ciation with ED in comparison to the non-PD
presence of stem cells in the normal tunica albug-
population [35,38,39,41]. The association with
inea may explain the ﬁbrotic and osteogenic pro-
Dupuytren’s disease was only investigated since
gression of the PD plaque upon the release of
1999 in two studies, where it was shown to be
cytokines following microtrauma to the penis that
highly signiﬁcant in the older population , and
would stimulate this cell lineage commitment.
the use of potassium paraminobenozoate, more
PD—PATHOGENESIS GRADE C
recent articles showed a signiﬁcant reduction in
PD is a wound healing disorder occurring
plaque size but no change in pain or improvement
in a presumed genetically susceptible in-
of the curvature . These results, although
dividual whose tunica albuginea responds
encouraging, will need to be conﬁrmed in future
inappropriately to an inciting event (i.e.,
trauma) with a proliferative, fibrotic reac-
tion resulting in an exuberant, inelastic scar.
A closer understanding of the etiopatho-
physiology is not yet established.
therapy prescribed by urologists for treating PD. However, recent double-blind, placebo con-trolled, randomized studies showed nonsigniﬁcant
improvement in pain, curvature, and plaque size,
As a result of the lack of a clear understanding
when compared with placebo [114,115].
of the etiopathophysiology, a cure has not beenfound. Therefore, a variety of treatment options
have been used. The most current therapies are
In 1992, Ralph et al. conﬁrmed that the daily
reviewed. The value of many published reports has
administration of Tamoxifen 20 mg twice daily
been questioned as most were not well controlled,
can induce signiﬁcant improvement in penile
often had a small number of subjects in various
pain, curvature, and plaque size in the early
phases of stability and with limited reports on
stages of the disease . However, these
objective measures of deformity change. Studies
encouraging results have not been conﬁrmed by
focus on reduction of pain that appears to resolve
with time untreated, and reduction of plaque size,which has never been found to correlate with
curvature improvement. In the opinion of the
Although initial studies showed that colchicine
authors reduction of erect penile deformity (i.e.,
might be also effective in the early phase of the
curve, narrowing, shortening) is the most critical
disease according to the ﬁnding of two recent
studies [118,119], recent series have showed thatcolchicine is no better than placebo .
THERAPY GRADE C
Although the administration of vitamin E and
Men with early phase disease (i.e.,
colchicine in isolation has been proved to be inef-
months induration) manifest by unstable or
fective, a recent double-blind randomized study
progressive deformity and painful erections
has showed that the administration of a combina-
as well as those not psychologically ready
tion of vitamin E and colchicine can induce sig-
or interested in surgery may be considered
niﬁcant improvement in plaque size, curvature,
candidates for nonsurgical therapy.
and pain during the initial phase of PD .
NONSURGICAL TREATMENT OVER-
VIEW GRADE C
Although initial studies fail to demonstrate any
Nonsurgical treatment has limited evidence
efﬁcacy of this combination in the treatment
of benefit, but multiple reports of deformity
of PD, recent data suggest that propionyl-l-
stabilization or reduction makes it reason-
carnitine and verapamil are effective in terms of
able to offer EMDA, and/or intralesional
plaque size reduction, pain, and penile curvature
injection of verapamil or interferon, and/or
PentoxifyllineIncreased levels of nitric oxide levels may be effec-
tive in preventing progression of PD or revers-
ing its ﬁbrosis as described by Brant et al. .
Although initial studies [110,111] showed only a
Further studies will be required to conﬁrm these
minimal improvement in symptoms of PD with
ORAL THERAPY GRADE B
There is evidence that there is no benefit
Intralesional injection may be used with the
with respect to deformity reduction with
any oral therapy, including Vitamin E,
Steroids—no objective measures of thera-
peutic benefit. GRADE D
tamoxifen, and carnitine.
Verapamil—appears to make scientific sense
but no large scale placebo-controlled
Although six studies using injectable corticoster-
oids for the treatment of PD showed positive out-
controlled trial showed an outcome
comes from treatment, the authors believe that the
therapeutic effects were because of the mechanical
effects of the injection and not to the drug action
Collagenase—Several small noncontrolled
trials showed limited benefit. It is cur-
rently being studied in a phase 2b trial.
Although the prospective, randomized, placebo-controlled study of Gelbard failed to demonstrate
Other Noninvasive Therapy
any clinical beneﬁt with the use of intralesionalinjections of collagenase , a recent study has
reported signiﬁcant decreases in deviation angle,
Although initial studies failed to demonstrate
any efﬁcacy of extracorporeal shock wave therapy(ESWT) for the treatment of PD [142–144], more
recent studies suggest a possible role of ESWL in
In vitro studies verapamil has been shown to inter-
fere with Peyronie’s plaque derived ﬁbroblast cel-lular proliferation and Levine et al. reported that
intralesional verapamil injection induces a signi-
THERAPY GRADE B
ﬁcant reduction in penile curvature [133–136].
There is evidence that ESWT does not
These encouraging results have been conﬁrmed by
improve PD-related deformity.
two subsequent studies, while one failed to dem-onstrate any effectiveness of this treatment [137–
Athough two studies proved the efﬁcacy of ionto-
Although large scale, placebo-controlled trials
phoresis using dexamethasone, verapamil, and
have not been conducted, intralesional Verapamil
lidocaine in terms of reductions of pain, plaque size,
injections could be recommended for the treat-
and curvature [148,149], a recent series of Green-
ment of noncalciﬁed acute or chronic plaques to
stein and Levine suggests that the only role for
stabilize disease progression or possibly reduce
iontophoresis is for the improvement of pain .
Hellstrom and associates conducted a singleblind,
multicenter, placebo-controlled parallel study that
As there are no independent controlled
showed that intralesional interferon alpha-2B may
trials and no evidence of adequate levels
be beneﬁcial for men with PD . These ﬁnd-
within the tunica albuginea, no recommen-
ings offer the largest and best-controlled trial of
dation is possible for topical Verapamil.
intralesional therapy for PD, as well as supports its
use and demonstrates the lack of clinical beneﬁt
IONTOPHORESIS GRADE C
following intralesional injection of saline. It is sig-
niﬁcantly more costly than verapamil and has been
of reduced deformity following ionto-
associated with ﬂu-like side effects. However, a
phoresis treatment using verapamil and
recent study failed to demonstrate any efﬁcacy of
It is well-documented that gradual expansion of
I. When rigidity adequate preoperatively with or without
tissue by traction, also known as mechanotrans-
duction, results in the formation of new connective
tissue by cellular proliferation in several tissue
models including bone, muscle, and Dupuytren’s
iii. Predicted loss of length < 20% erect length
scar [151–153]. However, penile traction has
B. Plaque Incision/ Partial Excision and grafting when
proved to have insigniﬁcant role in the manage-
of postoperative ED. The incision and grafting
Early evidence from two small noncon-
technique appears to increase the risk of postopera-
trolled prospective trials have reported a
tive ED, and therefore men who have borderline to
reduction of deformity and increased penile
inadequate erections preoperatively, which do not
length with traction therapy.
respond to pharmacological therapy, should avoidgrafting procedures or be prepared to need subse-quent penile prosthesis implantation . Lastly,
there is a risk of decreased sexual sensation. This
has been infrequently reported in the published
Surgery is indicated when the curvature impedes
literature, but it seems for the most part it rarely
adequate sexual penetration or there is an associ-
compromises orgasm and ejaculation. Surgical
ated ED that fails to respond to medical treatment
algorithms have been published to guide the choice
and should be offered only once the disease has
of surgical approach (, Table 2).
stabilized. In addition, patients who have extensive
Two main preoperative factors contribute to
plaque calciﬁcation are typically best treated with
this decision, including penile rigidity and severity
surgery, as nonsurgical approaches have not been
of deformity [161–163]. When rigidity is adequate,
shown to be beneﬁcial in this circumstance. Lastly,
with or without drug assistance, two approaches
the patient who wants the most rapid and reliable
have been suggested including tunica plication
result should select a surgical approach [26,156]
techniques, which are recommended when there is
a simple curvature of less than 60–70°, and no hour
Many of these men are depressed, have marked
glass deformity, and when the presumed loss of
reduction of self-esteem, and oftentimes have unat-
length caused by the plication will be less than
tainable expectations regarding the outcome from
20% of total erect length. For men who have more
surgical reconstruction . Therefore, a detailed
complex curvature greater than 60°, and/or a
discussion on persistent or recurrent curvature
destabilizing hourglass or hinge effect then plaque
should be initiated with the accepted goal of
incision, or partial plaque excision and grafting
making the patient “functionally straight,” which is
is preferred. It is important to stress that this
loosely deﬁned as a curvature of less than 20° .
approach is recommended for men who have good
Loss of length is most likely to occur with plication
procedures, particularly in those with ventral cur-vature . In addition, there may be diminishedrigidity, which has been shown to occur regardless
SURGICAL TREATMENT GRADE C
of the surgical approach. Clearly, those who have
Surgery remains the gold standard for cor-
suboptimal preoperative rigidity have a higher risk
recting erect penile deformity in the man
with stable disease.
Stable disease (6 months with no pain and stable deformity)
RECONSTRUCTION GRADE C
Compromised or inability to engage in coitusExtensive plaque calcification
Surgical reconstruction is indicated in
the man who has stable disease for _ 6
months, painless deformity, compromised,
or inability to engage in coitus secondary
from the convex (longer) side, then the edges
to deformity and/or inadequate rigidity,
are reaproximated to create the shortening effect
when there is extensive plaque calcification,
. Currently, there are many variations of the
and for the man who desires the most rapid
plication procedure, which include procedures
and reliable result.
where a portion of the tunica is not excised, butinstead plicated such as the Essed-Schroeder
technique . The Yachia technique utilizes
CONSENT GRADE D
the Heinke-Mikowitz principle where a vertical
The preoperative consent is critical to
incision is closed transversely so as to shorten the
set proper outcome expectations for the
convex side of the penis . The tunica albug-
patient. It is imperative to have a discussion
inea plication technique corrects the deformity
on the risks of persistent or recurrent
by plicating a series of paired incisions into the
curvature, loss of erect length, diminished
tunica without exposing the underlying cavern-
rigidity, and decreased sexual sensation.
osal tissue . The 16-dot procedure utilizesan extended Lembert type of suturing technique
SURGICAL ALGORITHM GRADE C
. In this procedure, a dorsal curve is cor-
Several surgical algorithms have been pub-
rected with sutures placed into the tunic on both
lished with general agreement that for men
sides of the urethra, then progressively tied down
with adequate preoperative rigidity, some
so as to create shortening and straightening.
form of tunica plication procedure is best
There is no tunica incision or tissue excision per-
for those with curvature less than 60° and
formed; therefore, the correction of deformity
with no hour-glass deformity resulting in
relies upon the nonabsorbable sutures. All these
a hinge effect. For those with more severe
procedures appear to adequately straighten the
>60° and/or hourglass) and good
penis with little risk of compromising erectile
preoperative rigidity, incision or partial
function. It is critical that during the per-
excision and grafting is recommended.
formance of any straightening procedure thesurgeon is able to induce an erection, usually byneedle injection of saline by pump or syringe(Table 3).
The advantages to the plication approach are
that they are simple, minimally invasive, and tend
This review of surgical approaches begins with
to preserve potency in most patients. The disad-
the plication procedures, which are designed to
vantages are that they can result in penile shorten-
shorten the longer side of the penis. If the cur-
ing, which has been shown to be exacerbated by
vature is in a dorsal direction, the plaque causes
correction of curvature greater than 60°, and/or
shortening of the dorsal aspect, and therefore
a ventral curvature where dorsal plication is
to correct the curvature with plication, the
ventral aspect is shortened. This approach is
Lastly, plication procedures may worsen an
based upon the Nesbit procedure where an erec-
existing hour-glass or hinge effect, particularly if
tion is created and a wedge of tunica is excised
Peyronie’s Disease published reports-plication procedures
most frequently used autologous graft currently
in use is saphenous vein, which requires a separate
incision to harvest, adding a risk of local side
There is no evidence that one surgical
effects, and longer operating time with a second
approach provides better outcomes over
incision to heal. Synthetic grafts were used histori-
another, but curvature correction can be
cally, including polyester and polytetraﬂouroe-
expected with low risk of new ED or sensory
thylene, but these have not been met with
enthusiasm because of the increased risk of infec-tion, an unnatural feel and may have the potential
Incision or Partial Excision and Grafting Techniques
for more local inﬂammation and ﬁbrosis .
Surgical grafting techniques include plaque inci-
The modern era of grafts include off-the-shelf
sion or partial excision. Historically, total plaque
processed human cadaveric tissue or xenografts.
excision was designed to “remove the diseased
These are felt to be advantageous because they can
tunica,” but this causes an unacceptably high rate
reduce operating time substantially, they appear to
of postoperative ED. This has been suggested to
have similar midterm outcome results as compared
occur as a result of a compromised veno-occlusive
with autologous grafts, and there is no harvest
mechanism, because of the changes in the relation-
comorbidity. These grafts include human and
ship between the cavernosal tissue and the overly-
bovine pericardium, porcine small intestinal sub-
ing tunic or graft . Therefore, minimizing the
mucosa, and porcine and human dermis. All these
excision or making simple releasing incisions have
grafts undergo an extensive processing to clear the
been recommended so a smaller graft may be used
tissue of cells, bacteria, viruses, and presumably
prions. As of this time there has been no report
The search for the ideal graft continues. As of
of host viral infection secondary to processed
this time, no ideal graft has been identiﬁed, which
allograft or xenograft implantation. The operative
would take reliably, not contract, be resistant to
procedure is done essentially the same for all graft-
infection and preserve erectile capacity 
ing techniques—an artiﬁcial erection is created
demonstrating the curvature and the penis is typi-
Currently, it appears that the nature of the graft
cally degloved using a circumcising incision allow-
is less likely the determining factor with respect to
ing exposure of the entire shaft of the penis. In the
postoperative ED. On the other hand, it is most
area of maximum curvature, Buck’s fascia contain-
likely a result of patient selection with respect to
ing the neurovascular bundle is elevated, either
preoperative erectile status and operative tech-
from a pair of parallel incisions lateral to the ure-
nique . Larger grafts, men older than 60 years
thral ridge allowing elevation of Buck’s fascia
old, and those with ventral grafting also appear to
dorsally, or by coming through the bed of the
have a higher risk of postoperative ED [162,175–
deep dorsal vein. It is felt that the deep dorsal vein
177]. A variety of autologous grafts have been
approach may not offer adequate lateral exposure,
used including dermis, tunica vaginalis, temporalis
which would be especially important for patients
fascia, buccal mucosa, and fascia lata . The
who have severe lateral indentation or hour-glassdeformity. The elevation process is best performedwith loupe magniﬁcation and bi-polar electrocau-
tery so as to reduce the likelihood of injury to theneurovascular tissues. Once Buck’s fascia is pro-
perly elevated an artiﬁcial erection is recreated,
demonstrating the area of maximum deformity.
Surgeons differ in their approach as to whether a
simple modiﬁed H-like incision should be made to
the area of maximum curvature or whether partial
plaque excision is recommended, particularly
when there is signiﬁcant indentation and/or calci-
ﬁcation. Regardless, the goal is to remove as little
plaque as possible, but to allow proper correction
of the deformity by expanding the tunic in both
Porcine small intestinal submucosa
girth and length. Edygio has championed the geo-
metric principle approach to graft sizing .
This technique has proven useful in his hands, but
and a loss of length was noted in 35% . At the
a recent report suggested a higher risk of postop-
2004 Annual Meeting of the American Urological
erative ED . Once the graft is positioned,
Association Society, Montorsi et al. reported on 50
Buck’s fascia is reapproximated to provide support
patients with a 5-year follow-up after venous graft-
and a vascularized cover over the graft.
ing where there was either persistent or recurrentcurvature in 12%, length loss in 100%, post-
Postoperative Care and Rehabilitation
operative ED in 22%, diminished orgasm in 41%,
Following surgery, postoperative rehabilitation
and overall patient satisfaction of only 60% .
is recommended to enhance recovery of erectile
Taylor and Levine recently reported a mean
function. Massage and stretch therapy, is per-
follow-up of just short of 5 years on 111 patients
formed by grasping the glans penis and pulling it
undergoing partial plaque excision with processed
gently and repeatedly away from the body while
human pericardial grafting where the patients
also gently massaging the graft area. This is initi-
reported persistent or recurrent curvature of
ated 2 weeks after surgery and performed twice a
greater than 20° in 8% (none required surgical
day for 4 weeks. It is advised that the patient’s
correction), a measured loss of stretched penile
partner get involved in the rehabilitation process to
length was found in 47%, but was subjectively
lessen the anxiety associated with the resumption of
reported by 65% of patients. The postoperative
sexual activity for both partners. Bedtime phos-
ED rate was 24% with 31% noting diminished
phodiesterase inhibitors have been recommended
sensation, but 89% experienced normal orgasm.
to begin 7–10 days after surgery and to be main-
Overall, patient satisfaction was reported at 76%
tained for 6 weeks, in order to enhance nocturnal
. Postoperative traction therapy had not been
erections, stretch the tissue, encourage nourish-
ment of the graft , and possibly reduce the risk
Recent studies have also examined the risk of
of postoperative ED. Finally, the use of external
postoperative ED following penile grafting proce-
penile traction therapy has been noted to reduce
dures [175,177]. For the most part, no signiﬁcant
postoperative penile shortening for patients who
contribution was found because of the duration of
have undergone either placation or grafting pro-
disease, vascular risk factors (including diabetes,
cedures. Traction is initiated 2–3 weeks post-
hypertension, elevated lipids, and smoking), a
operatively when the circumcising incision has
dorsal or lateral curvature, graft or tunica defect
adequately healed and is performed on a daily basis
size, or whether there was preoperative narrowing
for a minimum of 2–8 hours for 3 months .
or hinge effect. A higher risk of ED was found in
Table 5 outlines the results from published
those who underwent grafting for ventral curva-
reports on grafting, on average 74–100% of
ture and there was a trend toward increased ED
patients were adequately straight, with a post-
risk for men over the age of 60 . In this
published analysis, the primary component that
Kalsi et al. studied 40 patients who underwent
helped predict an increased risk of postoperative
vein grafting and followed for at least 5 years.
ED was when the patient reported preoperative
They reported a postoperative ED rate of 22.5%
internal tissue expander and will likely result in
correction of deformity in 6–9 months. On the
other hand, if there is substantial residual curva-
There is no evidence that surgical outcomes
ture, then releasing incisions can be made on the
are consistently better with one graft type,
concave side, often times through the same scrotal
and overall there is an increased risk of post-
incision or may require degloving of the penis with
operative ED. Autologous grafts require
elevation of Buck’s fascia. If these incisions create
more time and a second incision. Allograft
a tunic defect greater than 2 cm in any dimension,
and Xenograft procedures appear shorter
patching is recommended to decrease the risk of
in duration with no reported transmission
cicatrix contracture resulting in recurrent curva-
of disease. Synthetic grafts increase the risk
ture or herniation of the cylinders. An off-the-shelf
of infection and are not recommended.
graft is now recommended to ﬁx the tunic defect.
Freshly harvested dermal grafts are not recom-mended as there is risk of transferring bacteria
Penile Prosthesis Implantation with
within the dermal tissue increasing the possibility
Finally, for those men who have poor qualityerections and/or do not respond adequatelyto pharmacological therapy for their ED, penile
prosthesis implantation is recommended. Table 6
reviews the recommended surgical algorithm for
Penile prosthesis implantation with addi-
tional maneuvers to correct the deformity is
Prosthesis alone may result in satisfactory
recommended when there is preoperative
straightening of the penis for those with mild defor-
ED not responsive to oral medication (phos-
mity, but when residual curvature is more than 30°,
phodiesterase type 5 Inhibitors)
manual modeling is recommended . Manualmodeling should be performed with care. Once
the prosthesis is placed and the corporotomies are
closed, the prosthesis is inﬂated with a surrogate
(i.e., outside the body) reservoir of saline to dem-
following maneuvers are recommended
onstrate the deformity. The surgeon will then
including manual modeling followed by
model the penis by bending it in the contralateral
plaque incision if the residual erect curva-
direction to the curvature maintaining the pressure
ture exceeds 30°. If a tunica defect in excess
on the bent penis for 30–60 seconds. The tubing
of 2 cm is noted after incision, then grafting
between the pump and the cylinders should be
the defect is recommended to reduce the
occluded with rubber shod hemostats, so as to
risk of postoperative recurrent curvature
protect the pump from high pressure damage. In
or cylinder herniation. Autologous dermal
addition, when performing the modeling process,
grafts should not be placed over a prosthesis
pressure on the glans penis should be avoided to
as a result of the increased risk of infection.
prevent a urethral erosion by the cylinder tip. Analternative approach is to pre-place pliation sutures
PD SURGERY—OVERVIEW GRADE D
in the 16-dot method before implanting the pros-
Following published surgical algorithms is
thesis and then tying them down to correct the
imperative, as well as obtaining a preopera-
curvature. Regardless of the approach, if there is
tive consent to set proper outcome expecta-
residual curve less than 30°, no further treatment
tions for the patient. A plication procedure
is recommended, as the prosthesis will act as an
is indicated for less severe deformity (
and when there is borderline ED, while
grafting is reserved for severe deformity
Surgical algorithm with penile prosthesis
>60–70° Ϯ hinge with normal erectile func-
tion) and requires an experienced surgical
• Manual modeling if residual curve >30°
team. Lastly, prosthesis placement is indi-
• Plaque releasing incision if residual curve after modeling >30°
cated with additional maneuvers for those
• Graft tunica if defect >2.0 cm to prevent implant herniation or
men with refractory ED and PD.
5 Kadioglu A, Tefekli A, Erol B, Oktar T, Tunc M, Tellaloglu S.
A retrospective review of 307 men with Peyronie’s disease.
This review is intended to be a guide to making
decisions about surgical correction of PD. The
6 Mulhall JP, Schiff J, Guhring P. An analysis of the natural
intent is that it will be useful to the practicing
history of Peyronie’s disease. J Urol 2006;175:2115–8.
7 Levine LA, Greenﬁeld JM. Establishing a standardized evalu-
surgeon so that they may provide appropriate
ation of the man with Peyronie’s disease. Int J Impot Res
advice to their patients regarding the proper
surgical procedure. The most critical part of
8 Pryor J, Akkus E, Alter G, Jordan G, Lebret T, Levine L,
the surgeon’s role in the preoperative phase is to
Mulhall J, Perovic S, Ralph D, Stackl W. Peyronie’s disease.
J Sex Med 2004;1:110–5.
set appropriate expectations for the patient and
9 Pryor JP, Ralph DJ. Clinical presentations of Peyronie’s
to review the potential complications of surgery,
disease. Int J Impot Res 2002;14:414–7.
including incomplete straightening, recurrent
10 Bella AJ, Sener A, Foell K, Brock GB. Nonpalpable scarring
curvature, shaft shortening, diminished sensation,
of the penile septum as a cause of erectile dysfunction: Anatypical form of Peyronie’s disease. J Sex Med 2007;4:226–30.
and ED. Although surgical correction of PD has
11 Vernet D, Nolazco G, Cantini L, Magee TR, Qian A, Rajfer
historically had a negative reputation, the more
J, Gonzalez-Cadavid NF. Evidence that osteogenic progeni-
recent reﬁnements in technique make it a viable
tor cells in the human tunica albuginea may originate fromstem cells: Implications for peyronie disease. Biol Reprod
and successful treatment option for the properly
12 Ohebshalom M, Mulhall J, Guhring P, Parker M. Measure-
ment of penile curvature in Peyronie’s disease patients: Com-
parison of three methods. J Sex Med 2007;4:199–203.
FRCS(Urol), Institute of Urology, 145 Harley St,
13 Rosen R, Catania J, Lue T, Althof S, Henne J, Hellstrom W,
London W1G 6BJ; Tel: +44 207 486 3805; Fax: +44 207
Levine L. Impact of Peyronie’s disease on sexual and psycho-social functioning: Qualitative ﬁndings in patients and con-
14 Smith JF, Conti S, Walsh TJ, Turek P, Lue T. Risk factors for
emotional and relationship problems in Peyronie’s disease. JSex Med 2008;5:2179–84.
15 Nelson CJ, Diblasio C, Kendirci M, Hellstrom W, Guhring
Statement of Authorship
P, Mulhall JP. The chronology of depression and distress inmen with Peyronie’s disease. J Sex Med 2008;5:1985–90.
16 Amin Z, Patel U, Friedman EP, Vale JA, Kirby R, Lees WR.
(a) Conception and Design
Colour Doppler and duplex ultrasound assessment of Peyro-
(b) Acquisition of Data
nie’s disease in impotent men. B J Rad 1993;66:398–402.
17 Kadioglu A, Oktar T, Kandirali E, Kendirci M, Sanli O,
(c) Analysis and Interpretation of Data
Ozsoy C. Incidentally diagnosed Peyronie’s disease in menpresenting with erectile dysfunction. Int J Impot Res2004;16:540–3.
18 Gasior BL, Levine FJ, Howannesian A, Krane RJ, Goldstein I.
(a) Drafting the Article
Plaque-associated corporal venoocclusive dysfunction in idio-
(b) Revising It for Intellectual Content
pathic Peyronie’s disease: A pharmacocavernosometric andpharmacocavernosographic study. World J Urol 1990;8:90–6.
19 Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J,
Mishra A. The International Index of Erectile function(IIEF): A multidimensional scale for the assessment of erec-
(a) Final Approval of the Completed Article
tile dysfunction. Urology 1997;49:822–30.
20 Hauck EW, Hackstein N, Vosshenrich R, Diemer T,
Schmelz HU, Bschleipfer T, Schroeder-Printzen I, WeidnerW. Diagnostic value of magnetic resonance imaging in Pey-
ronie’s disease—A comparison both with palpation and ultra-
1 Lue TF, Giuliano F, Montorsi F, Rosen RC, Andersson KE,
sound in the evaluation of plaque formation. Eur Urol
Althof S, Christ G, Hatzichristou D, Hirsch M, Kimoto Y,
Lewis R, McKenna K, MacMahon C, Morales A, Mulcahy J,
21 Aversa A, Sarteschi LM. The role of penile colorduplex ultra-
Padma-Nathan H, Pryor J, de Tejada IS, Shabsigh R, Wagner
sound for the evaluation of erectile dysfunction. J Sex Med
G. Summary of the recommendations on sexual dysfunctions
22 Kadioglu A, Tefekli A, Erol H, Cayan S, Kandirali E.
2 Schwarzer U, Sommer F, Klotz T, Braun M, Reifenrath B,
Color Doppler ultrasound assessment of penile vascular
Engelmann U. The prevalence of Peyronie’s disease: Results
system in men with Peyronie’s disease. Int J Impot Res
of a large survey. BJU Int 2001;88:727–30.
3 Deveci S, Hopps C, O’Brien K, Parker M, Guhring P,
23 LaRochelle JC, Levine LA. A survey of primary care physi-
Mulhall JP. Deﬁning the clinical characteristics of peyronie’s
cians and urologists regarding Peyronie’s disease. J Sex Med
disease in young men. J Sex Med 2007;4:485–90.
4 Kendirci M, Trost L, Sikka SC, Hellstrom GJ. Diabetes mel-
24 Müller A, Mulhall JP. Peyronie’s disease intervention trials:
litus is associated with severe Peyronie’s disease. BJU Int
Methodological challenges and issues. J Sex Med 2009;6:848–
25 Smith JF, Walsh TJ, Lue TF. Peyronie’s disease: A critical
ronie’s disease. In: Levine LA, ed. Current clinical urology:
appraisal of current diagnosis and treatment. Int J Impot Res
Peyronie’s disease, a guide to clinical management. Totowa,
26 Bella AJ, Perelman MA, Brant WO, Lue TF. Peyronie’s
46 Sasso F, Gulino G, Falabella R, D’Addessi A, Sacco E,
disease (CME). J Sex Med 2007;4:1527–38.
D’Onofrio A, Bassi PF. Peyronie’s disease: Lights and
27 Taylor FL, Levine LA. Peyronie’s disease. Urol Clin North
47 Devine CJ Jr, Somers KD, Jordan SG, Schlossberg SM.
28 Greenﬁeld JM, Levine LA. Peyronie’s disease: Etiology,
Proposal: Trauma as the cause of the Peyronie’s lesion. J Urol
epidemiology and medical treatment. Urol Clin North Am
48 Somers KD, Dawson DM. Fibrin deposition in Peyronie’s
29 Smith CJ, McMahon C, Shabsigh R. Peyronie’s disease: The
disease plaque. J Urol 1997;157:311–5.
epidemiology, aetiology and clinical evaluation of deformity.
49 Van de Water L. Mechanisms by which ﬁbrin and ﬁbronectin
appear in healing wounds: Implications for Peyronie’s
30 Rhoden EL, Teloken C, Ting HY, Lucas ML, Teodósio da
Ros C, Ary Vargas Souto C. Prevalence of Peyronie’s disease
50 Davila HH, Magee TR, Zuniga FI, Rajfer J, Gonzalez-
in men over 50-year-old from Southern Brazil. Int J Impot
Cadavid NF. Peyronie’s disease associated with increase in
plasminogen activator inhibitor in ﬁbrotic plaque. Urology
31 Mulhall JP, Creech SD, Boorjian SA, Ghaly S, Kim ED,
Moty A, Davis R, Hellstrom W. Subjective and objective
51 Ehrlich HP. Scar contracture: Cellular and connective tissue
analysis of the prevalence of Peyronie’s disease in a popula-
aspects in Peyronie’s disease. J Urol 1997;157:316–9.
tion of men presenting for prostate cancer screening.
52 Davila HH, Ferrini MG, Rajfer J, Gonzalez-Cadavid NF.
Fibrin as an inducer of ﬁbrosis in the tunica albuginea of
32 La Pera G, Pescatori ES, Calabrese M, Bofﬁni A, Colombo F,
the rat: A new animal model of Peyronie’s disease. BJU Int
Andriani E, Natali A, Vaggi L, Catuogno C, Giustini M,
Taggi F. SIMONA Study Group. Peyronie’s disease: Preva-
53 Davila HH, Magee TR, Vernet D, Rajfer J, Gonzalez-
lence and association with cigarette smoking. A multicenter
Cadavid NF. Gene transfer of inducible nitric oxide synthase
population-based study in men aged 50–69 years. Eur Urol
complementary DNA regresses the ﬁbrotic plaque in an
animal model of Peyronie’s disease. Biol Reprod 2004;71:
33 Kumar B, Narang T, Gupta S, Gulati M. A clinico-
aetiological and ultrasonographic study of Peyronie’s disease.
54 Zargooshi J. Trauma as the cause of Peyronie’s disease: Penile
fracture as a model of trauma. J Urol 2004;172:186–8.
34 El-Sakka AI. Prevalence of Peyronie’s disease among patients
55 El-Sakka AI, Selph CA, Yen TS, Dahiya R, Lue TF.
with erectile dysfunction. Eur Urol 2006;49:564–69.
The effect of surgical trauma on rat tunica albuginea. J Urol
35 Tefekli A, Kandirali E, Erol B, Tunc M, Kadioglu A. Peyro-
nie’s disease: A silent consequence of diabetes mellitus. Asian
56 Schiavino D, Sasso F, Nucera E, Alcini E, Gulino G, Milani
A, Patriarca G. Immunologic ﬁndings in Peyronie’s disease: A
36 Usta MF, Bivalacqua TJ, Tokatli Z, Rivera F, Gulkesen KH,
controlled study. Urology 1997;50:764–8.
Sikka SC, Hellstrom WJ. Stratiﬁcation of penile vascular
57 Noss MB, Day NS, Christ GJ, Melman A. The genetics and
pathologies in patients with Peyronie’s disease and in men
immunology of Peyronie’s disease. Int J Impot Res 2000;
with erectile dysfunction according to age: A comparative
58 Hauck EW, Hauptmann A, Weidner W, Bein G, Hackstein
37 Usta MF, Bivalacqua TJ, Jabren GW, Myers L, Sanabria J,
H. Prospective analysis of HLA classes I and II antigen
Sikka SC, Hellstrom WJ. Relationship between the severity
frequency in patients with Peyronie’s disease. J Urol 2003;
of penile curvature and the presence of comorbidities in men
with Peyronie’s disease. J Urol 2004;171:775–9.
59 Hauck EW, Hauptmann A, Haag SM, Bohnert A, Weidner
38 El-Sakka AI, Tayeb KA. Peyronie’s disease in diabetic
W, Bein G, Hackstein H. Alpha-1-antitrypsin levels and
patients being screened for erectile dysfunction. J Urol
genetic variation of the alpha-1-antitrypsin gene in Peyro-
nie’s disease. Eur Urol 2004;46:623–8; discussion 628.
39 Tefekli A, Kandirali E, Erol H, Alp T, Köksal T, Kadioglu A.
60 Hauck EW, Hauptmann A, Schmelz HU, Bein G, Weidner
Peyronie’s disease in men under age 40: Characteristics and
W, Hackstein H. Prospective analysis of single nucleotide
outcome. Int J Impot Res 2001;13:18–23.
polymorphisms of the transforming growth factor beta-1
40 Carrieri MP, Serraino D, Palmiotto F, Nucci G, Sasso F. A
gene in Peyronie’s disease. J Urol 2003;169:369–72.
case-control study on risk factors for Peyronie’s disease.
61 Ralph DJ, Schwartz G, Moore W, Pryor JP, Ebringer A,
Bottazzo GF. The genetic and bacteriological aspects of
41 Perimenis P, Athanasopoulos A, Gyftopoulos K, Katsenis G,
Peyronie’s disease. J Urol 1997;157:291–4.
Barbalias G. Peyronie’s disease: Epidemiology and clinical
62 Domes T, De Young L, O’Gorman DB, Gan BS, Bella AJ,
presentation of 134 cases. Int Urol Nephrol 2001;32:691–4.
Brock G. Is there a role for proteomics in Peyronie’s disease?
42 Bjekic MD, Vlajinac HD, Sipetic SB, Marinkovic JM. Risk
factors for Peyronie’s disease: A casecontrol study. BJU Int
63 Ferrini MG, Vernet D, Magee TR, Shahed A, Qian A, Rajfer
J, Gonzalez-Cadavid NF. Antiﬁbrotic role of inducible nitric
43 Arafa M, Eid H, El-Badry A, Ezz-Eldine K, Shamloul R. The
oxide synthase. Nitric Oxide 2002;6:283–94.
prevalence of Peyronie’s disease in diabetic patients with
64 Iacono F, Barra S, de Rosa G, Boscaino A, Lotti T. Micro-
erectile dysfunction. Int J Impot Res 2007;19:213–7.
structural disorders of tunica albuginea in patients affected by
44 Gonzalez-Cadavid NF, Rajfer J. Experimental models of
impotence. Eur Urol 1994;26:233–39.
Peyronie’s disease: Implications for new therapies. J Sex Med
65 Anafarta K, Bedük Y, Uluoglu O, Aydos K, Baltaci S.
The signiﬁcance of histopathological changes of the normal
45 Gonzalez-Cadavid NF, Rajfer J. Experimental models for the
tunica albuginea in Peyronie’s disease. Int Urol Nephrol
study of the cellular and molecular pathophysiology of Pey-
66 Brock G, Hsu GL, Nunes L, von Heyden B, Lue TF. The
development of ﬁbrotic plaques in a rat model of Peyronie’s
anatomy of the tunica albuginea in the normal penis and
Peyronie’s disease. J Urol 1997;157:276–81.
83 Cantini LP, Ferrini MG, Vernet D, Magee TR, Qian A,
67 Mirone V, Imbimbo C, Palmieri A, Longo N, Fusco F,
Gelfand RA, Rajfer J, Gonzalez-Cadavid NF. Proﬁbrotic role
Tajana G. A new biopsy technique to investigate Peyronie’s
of myostatin in Peyronie’s disease. J Sex Med 2008;5:1607–
disease associated histologic alterations: Results with two dif-
ferent forms of therapy. Eur Urol 2002;42:239–44; discussion
84 Wynn TA. Cellular and molecular mechanisms of ﬁbrosis.
68 Somers KD, Sismour EN, Wright GL Jr, Devine CJ Jr,
85 Piao S, Ryu JK, Shin HY, Zhang L, Song SU, Han JY, Park
Gilbert DA, Horton CE. Isolation and characterization of
SH, Kim JM, Kim IH, Kim SJ, Suh JK. Repeated intratunical
collagen in Peyronie’s disease. J Urol 1989;141:629–31.
injection of adenovirus expressing transforming growth
69 Gentile V, Modesti A, La Pera G, Vasaturo F, Modica A,
factor-beta1 in a rat induces penile curvature with tunical
Prigiotti G, Di Silverio F, Scarpa S. Ultrastructural and
ﬁbrotic plaque: A useful model for the study of Peyronie’s
immunohistochemical characterization of the tunica albug-
disease. Int J Androl 2008;31:346–53.
inea in Peyronie’s disease and veno-occlusive dysfunction.
86 Lucattelli M, Lunghi B, Fineschi S. A new mouse model
of Peyronie’s disease: An increased expression of hypoxia-
70 Davis CJ Jr. The microscopic pathology of Peyronie’s
induciblefactor-1 target genes during the development of
penile changes. Int J Biochem Cell Biol 2008;40:2638–48.
71 Hirano D, Takimoto Y, Yamamoto T, Hirakata H, Kawata N.
87 Somers KD, Dawson DM, Wright GL Jr, Leffell MS, Rowe
Electron microscopic study of the penile plaques and adjacent
MJ, Bluemink GG, Vande Berg JS, Gleischman SH, Devine
corpora cavernosa in Peyronie’s disease. Int J Urol 1997;
CJ Jr, Horton CE. Cell culture of Peyronie’s disease plaque
and normal penile tissue. J Urol 1982;127:585–8.
72 Vernet D, Ferrini MG, Valente EG, Magee TR, Bou-Gharios
88 Mulhall JP, Nicholson B, Pierpaoli S, Lubrano T, Shankey
G, Rajfer J, Gonzalez-Cadavid NF. Effect of nitric oxide on
TV. Chromosomal instability is demonstrated by ﬁbroblasts
the differentiation of ﬁbroblasts into myoﬁbroblasts in the
derived from the tunica of men with Peyronie’s disease. Int J
Peyronie’s ﬁbrotic plaque and in its rat model. Nitric Oxide
89 Mulhall JP, Branch J, Lubrano T, Shankey TV. Perturbation
73 Eyden B. The myoﬁbroblast: Phenotypic characterization as
of cell cycle regulators in Peyronie’s disease. Int J Impot Res
a prerequisite to understanding its functions in translational
medicine. J Cell Mol Med 2008;12:22–37.
90 Mulhall JP, Thom J, Lubrano T, Shankey TV. Basic ﬁbro-
74 Vernet D, Magee T, Qian A, Nolazco G, Rajfer J, Gonzalez-
blast growth factor expression in Peyronie’s disease. J Urol
Cadavid N. Phosphodiesterase type 5 is not upregulated
by tadalaﬁl in cultures of human penile cells. J Sex Med
91 Mulhall JP, Branch J, Lubrano T, Shankey TV. Radiation
increases ﬁbrogenic cytokine expression by Peyronie’s disease
75 Vande Berg JS, Devine CJ Jr, Horton CE, Somers KD,
ﬁbroblasts. J Urol 2003;170:281–4.
Wright GL Jr, Leffell MS, Dawson DM, Gleischman SH,
92 Mulhall JP, Anderson MS, Lubrano T, Shankey TV. Peyro-
Rowe MJ. Mechanisms of calciﬁcation in Peyronie’s disease.
nie’s disease cell culture models: Phenotypic, genotypic and
functional analyses. Int J Impot Res 2002;14:397–405.
76 El-Sakka AI, Hassoba HM, Chui RM, Bhatnagar RS, Dahiya
93 Mulhall JP, Martin DJ, Lubrano T, Moser M, Kwon E, Wojcik
R, Lue TF. An animal model of Peyronie’s-like condition
E, Shankey TV. Peyronie’s disease ﬁbroblasts demonstrate
associated with an increase of transforming growth factor
tumorigenicity in the severe combined immunodeﬁcient
beta mRNA and protein expression. J Urol 1997;158:2284–
(SCID) mouse model. Int J Impot Res 2004;16:99–104.
94 Mulhall JP. Expanding the paradigm for plaque development
77 El-Sakka AI, Hassan MU, Nunes L, Bhatnagar RS, Yen TS,
in Peyronie’s disease. Int J Impot Res 2003;15(suppl 5):S93–
Lue TF. Histological and ultrastructural alterations in an
animal model of Peyronie’s disease. Br J Urol 1998;81:
95 Haag SM, Hauck EW, Eickelberg O, Szardening- Kirchner
C, Diemer T, Weidner W. Investigation of the antiﬁbrotic
78 El-Sakka AI, Bakircioglu ME, Bhatnagar RS, Yen TS,
effect of IFN-gamma on ﬁbroblasts in a cell culture model of
Dahiya R, Lue TF. The effects of colchicine on a Peyronie’s-
Peyronie’s disease. Eur Urol 2008;53:425–30; Epub 2007 Jun
like condition in an animal model. J Urol 1999;161:1980–
96 Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat
79 Bivalacqua TJ, Diner EK, Novak TE, Vohra Y, Sikka SC,
ML, Gabbiani G. The myoﬁbroblast: One function, multiple
Champion HC, Kadowitz PJ, Hellstrom WJ. A rat model of
origins. Am J Pathol 2007;170:1807–16.
Peyronie’s disease associated with a decrease in erectile activ-
97 Nolazco G, Kovanecz I, Vernet D, Gelfand RA, Tsao J,
ity and an increase in inducible nitric oxide synthase protein
Ferrini MG, Magee T, Rajfer J, Gonzalez-Cadavid NF.
expression. J Urol 2000;163:1992–8.
Effect of muscle-derived stem cells on the restoration of
80 Bivalacqua TJ, Champion HC, Leungwattanakij S, Yang DY,
corpora cavernosa smooth muscle and erectile function in the
Hyun JS, Abdel-Mageed AB, Sikka SC, Kadowitz PJ, Hell-
aged rat. BJU Int 2008;101:1156–64.
strom WJ. Evaluation of nitric oxide synthase and arginase in
98 Gonzalez-Cadavid NF. Mechanisms of penile ﬁbrosis. J Sex
the induction of a Peyronie’s-like condition in the rat. J
99 El-Sakka AI, Hassoba HM, Pillarisetty RJ, Dahiya R,
81 Valente EG, Vernet D, Ferrini MG, Qian A, Rajfer J,
Lue TF. Peyronie’s disease is associated with an increase in
Gonzalez-Cadavid NF. L-arginine and phosphodiesterase
transforming growth factor-beta protein expression. J Urol
(PDE) inhibitors counteract ﬁbrosis in the Peyronie’s ﬁbrotic
plaque and related ﬁbroblast cultures. Nitric Oxide 2003;9:
100 Lin CS, Lin G, Wang Z, Maddah SA, Lue TF. Upregulation
of monocyte chemoattractant protein 1 and effects of trans-
82 Ferrini MG, Kovanecz I, Nolazco G, Rajfer J, Gonzalez-
forming growth factor-beta 1 in Peyronie’s disease. Biochem
Cadavid NF. Effects of long-term vardenaﬁl treatment on the
Biophys Res Commun 2002;295:1014–9.
101 Wang Z, Lin G, Lue TF, Lin CS. Wogonin suppresses
119 Kadioglu A, Tefekli A, Köksal T, Usta M, Erol H. Treatment
cellular proliferation and expression of monocyte chemo-
of Peyronie’s disease with oral colchicine: Long-term results
attractant protein 1 in Peyronie’s plaque-derived cells. BJU
and predictive parameters of successful outcome. Int J Impot
102 Gonzalez-Cadavid NF, Rajfer J. The pleiotropic effects
120 Safarinejad MR. Therapeutic effects of colchicine in the
of inducible nitric oxide synthase on the physiology and
management of Peyronie’s disease: A randomized double-
pathology of penile erection. Curr Pharm Des 2005;11:4041–
blind, placebo-controlled study. Int J Impot Res 2004;16:
103 Del Carlo M, Cole AA, Levine LA. Differential calcium
121 Prieto Castro RM, Leva Vallejo ME, Regueiro Lopez JC,
Anglada Curado FJ, Alvarez Kindelan J, Requena Tapia MJ.
and tissue inhibitors of matrix metalloproteinases by
Combined treatment with vitamin E and colchicine in the
early stages of Peyronie’s disease. BJU Int 2003;91:522–4.
beta in Peyronie’s plaque ﬁbroblasts. J Urol 2008;179:2447–
122 Biagiotti G, Cavallini G. Acetyl-L-carnitine vs tamoxifen in
the oral therapy of Peyronie’s disease: A preliminary report.
104 Gelbard MK, James K, Riach P, Dorey F. Collagenase versus
placebo in the treatment of Peyronie’s disease: A double-
123 Cavallini G, Biagiotti G, Koverech A, Vitali G. Oral
blind study. J Urol 1993;149:56–8.
propionyl-l-carnitine and intraplaque verapamil in the
therapy of advanced and resistant Peyronie’s disease. BJU Int
disease: New insights into the cellular and molecular
pathology of Peyronie’s disease. Nat Clin Pract Urol 2005;
124 Brant WO, Dean RC, Lue TF. Treatment of Peyronie’s
disease with oral pentoxifylline. Nat Clin Pract Urol 2006;
106 Magee TR, Qian A, Rajfer J, Sander FC, Levine LA,
Gonzalez-Cadavid NF. Gene expression proﬁles in the Pey-
125 Winter CC, Khanna R. Peyronie’s disease: Results with
ronie’s disease plaque. Urology 2002;59:451–7.
dermo-jet injection of dexamethasone. J Urol 1975;114:898–
107 Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF.
Comparison of gene expression proﬁles between Peyronie’s
126 Desanctis PN, Furey CA Jr. Steroid injection therapy
disease and Dupuytren’s contracture. Urology 2004;64:399–
for Peyronie’s disease: A 10-year summary and review of
108 Ferrini MG, Kovanecz I, Sanchez S, Vernet D, Davila HH,
127 Teasley GH. Peyronie’s disease: A new approach. J Urol
Rajfer J, Gonzalez-Cadavid NF. Longterm continuous treat-
ment with sildenaﬁl ameliorates aging-related erectile dys-
128 Williams G, Green NA. The non-surgical treatment of
function and the underlying corporal ﬁbrosis. Biol Reprod
Peyronie’s disease. Br J Urol 1980;52:392–5.
129 Toksu E. Peyronie’s disease: A method of treatment. J Urol
109 Kovanecz I, Rambhatla A, Ferrini MG, Vernet D, Sanchez S,
Rajfer J, Gonzalez-Cadavid N. Chronic daily tadalaﬁl pre-
130 Furey CA Jr. Peyronie’s disease: Treatment by the local
vents the corporal ﬁbrosis and veno-occlusive dysfunction
injection of meticortelone and hydrocortisone. J Urol
(CVOD) that occurs following cavernosal nerve resection in
131 Cipollone G, Nicolai M, Mastroprimiano G, Iantorno R,
110 Zarafonetis CJD, Horrax TM. Treatment of Peyronie’s
Longeri D, Tenaglia R. Betamethasone versus placebo in
disease with potassium paraaminobenzoate (Potaba). J Urol
Peyronie’s disease. Arch Ital Urol Androl 1998;70:165–8.
132 Jordan GH. The use of intralesional clostridial collagenase
111 Shah PJR, Green NA, Adib RS, Pryor JP. A multicentre
injection therapy for Peyronie’s disease: A prospective,
doubleblind controlled clinical trial of potassium-para-
single-center, non-placebocontrolled study. J Sex Med 2008;
aminobenzoate (Potaba) in Peyronie’s disease. Prog Reprod
133 Levine LA, Merrick PF, Lee RC. Intralesional verapamil
112 Weidner W, Hauck EW, Schnitker J. Potassium para-
injection for the treatment of Peyronie’s disease. J Urol
aminobenzoate (POTABA) in the treatment of Peyronie’s
disease: A prospective, placebocontrolled, randomized study.
134 Levine LA. Treatment of Peyronie’s disease with intralesional
verapamil injection. J Urol 1997;158:1395–99.
113 Shindel AW, Bullock TL, Brandes S. Urologist practice pat-
135 Levine LA, Goldman K, Greenﬁeld J. Experience with intra-
terns in the management of Peyronie’s disease: A nationwide
plaque injection of verapamil for Peyronie’s disease. J Urol
survey. J Sex Med 2008;5:954–64; Epub 2007 Nov 27.
114 Pryor JP, Farell CR. Controlled clinical trial of vitamin E
136 Anderson MS, Shankey TV, Lubrano T, Mulhall JP.
in Peyronie’s disease. Prog Reprod Biol Med 1983;9:41–5.
Inhibition of Peyronie’s plaque ﬁbroblast proliferation
115 Safarinejad MR, Hosseini SY, Kolahi AA. Comparison of
by biologic agents. Int J Impot Res 2000;12(suppl 3):S25–
vitamin E and propionyl-Lcarnitine, separately or in combi-
nation, in patients with early chronic Peyronie’s disease: A
137 Rehman J, Benet A, Melman A. Use of intralesional verapamil
doubleblind, placebo controlled, randomized study. J Urol
to dissolve Peyronie’s disease plaque: A long-term single-
blind study. Urology 1998;51:620–6.
116 Ralph DJ, Brooks MD, Bottazzo GF, Pryor JP. The treat-
138 Bennet NE, Guhring P, Mulhall JP. Intralesional verapamil
ment of Peyronie’s disease with tamoxifen. Br J Urol 1992;
prevents the progression of Peyronie’s disease. J Urol 2007;
117 Teloken C, Rhoden EL, Grazziotin TM, Ros CT, Sogari PR,
139 Cavallini G, Modenini F, Vitali G. Open preliminary ran-
Souto CA. Tamoxifen versus placebo in the treatment of
domized prospective clinical trial of efﬁcacy and safety of
Peyronie’s disease. J Urol 1999;162:2003–5.
three different verapamil dilutions for intraplaque therapy of
118 Akkus E, Carrier S, Rehman J, Breza J, Kadioglu A, Lue TF.
Peyronie’s disease. Urology 2007;69:950–4.
Is colchicine effective in Peyronie’s disease? A pilot study.
140 Hellstrom WJ, Kendirci M, Matern R, Cockerham Y, Myers
L, Sikka SC, Venable D, Honig S, McCullough A, Hakim LS,
Nehra A. Single-blind, multicenter, placebo controlled, par-
158 Greenﬁeld JM, Lucas S, Levine LA. Factors affecting the loss
allel study to assess the safety and efﬁcacy of intralesional
of length associated with tunical albuginea plication for cor-
interferon alpha-2B for minimally invasive treatment for Pey-
rection of penile curvature. J Urol 2006;175:238–41.
ronie’s disease. J Urol 2006;176:394–8.
159 Levine LA, Greenﬁeld JM, Estrada CR. Erectile dysfunction
141 Inal T, Tokatli Z, Akand M, Ozdiler E, Yaman O. Effect of
following surgical correction of Peyronie’s disease and a pilot
intralesional interferon-alpha 2b combined with oral vitamin
study of the use of Sildenaﬁl citrate rehabilitation for postop-
E for treatment of early stage Peyronie’s disease: A random-
erative erectile dysfunction. J Sex Med 2007;5:241–7.
ized and prospective study. Urology 2006;67:1038–42.
160 Dimitriou R, Levine LA. A surgical algorithm for penile
142 Michel MS, Ptaschnyk T, Musial A, Braun P, Lenz ST, Alken
prosthesis placement in men with erectile failure and Peyro-
P, Köhrmann KU. Objective and subjective changes in
nie’s Disease. J Urol 1999;161:1014A.
patients with Peyronie’s disease after management with shock
161 Levine LA, Lenting E. A surgical algorithm for the treatment
wave therapy. J Endourol 2003;17:41–4.
of Peyronie’s disease. J Urol 1997;158:2149–52.
143 Strebel RT, Suter S, Sautter T, Hauri D. Extracorporeal
162 Mulhall JP, Anderson M, Parker M. A surgical algorithm for
shock wave therapy for Peyronie’s disease does not correct
men with combined Peyronie’s disease and erectile dysfunc-
penile deformity. Int J Impot Res 2004;16:448–51.
tion: Functional and satisfaction outcomes. J Sex Med
144 Hauck EW, Hauptmann A, Bschleipfer T, Schmelz HU,
Altinkilic BM, Weidner W. Questionable efﬁcacy of extra-
163 Ralph DJ, Minhas S. The management of Peyronie’s disease.
corporeal shock wave therapy in Peyronie’s disease: Results
of a prospective approach. J Urol 2004;171:269–99.
164 Ralph DJ, al-Akraa M, Pryor JP. The Nesbit operation for
145 Hauck EW, Mueller UO, Bschleipfer T, Schmelz HU,
Peyronie’s disease: 16-year experience. J Urol 1995;4:1362–3.
Diemer T, Weidner W. Extracorporeal shock wave therapy
165 Essed E, Schroeder F. New surgical technique for Peyronie’s
for Peyronie’s disease: Exploratory meta-analysis of clinical
166 Yachia D. Modiﬁed corporoplasty for the treatment of penile
146 Srirangam SJ, Manikandan R, Hussain J, Collins GN,
O’Reilly PH. Long-term results of extracorporeal shockwave
167 Gholami SS, Lue TF. Correction of penile curvature using
therapy for Peyronie’s disease. J Endourol 2006;20:880–4.
the 16-dot plication technique: A review of 132 patients. J
147 Palmieri A, Imbimbo C, Longo N, Fusco F, Verze P, Man-
giapia F, Creta M, Mirone V. A ﬁrst prospective, randomized,
168 Bella AJ, Brock GB. Minimally invasive intracorpal incision
double-blind, placebo- controlled clinical trial evaluating
of peyronie’s plaque. Peyronie’s Disease. In: Levine LA, ed. A
extracorporeal shock wave therapy for the treatment of Pey-
guide to clinical management. Totowa, NJ: Humana Press;
ronie’s disease. Eur Urol 2009;56:363–70.
148 Riedl CR, Plas E, Engelhardt P, Daha K, Pﬂüger H.
169 Daitch J, Angermeier K, Montague D. Modiﬁed corporo-
Iontophoresis for treatment of Peyronie’s disease. J Urol
plasty for penile curvature: Long-term results and patient
satisfaction. J Urol 1999;162:2006–9.
149 Di Stasi S, Giannantoni A, Stephen RL, Capelli G, Giurioli
170 Rolle L, Tamagnone A, Timpano M, Destefanis P, Fiori C,
A, Jannini EA, Vespasiani G. A prospective, randomized study
Ceruti C, Fontana D. The Nesbit operation for penile cur-
using transdermal electromotive administration of verapamil
vature: An easy and effective technical modiﬁcation. J Urol
and dexamethasone for Peyronie’s disease. J Urol 2004;171:
171 Savoca G, Scieri F, Petropaolo F, Garaffa G, Belgrano E.
150 Greenﬁeld JM, Shah SJ, Levine LA. Verapamil versus saline
Straightening corporoplasty for Peyronie’s disease: A review
in electromotive drug administration for Peyronie’s disease:
of 218 patients with median follow-up of 89 months. Eur
A double-blind, placebo controlled trial. J Urol 2007;177:
172 Syed AH, Abbasi Z, Hargreave TB. Nesbit procedure for
151 Li J, Duncan RL, Burr DB, Turner CH. L-type calcium
disabling Peyronie’s curvature: A median follow-up of 84
channels mediate mechanically induced bone formation in
vivo. J Bone Miner Res 2003;18:58–66.
173 Dalkin BL, Carter MF. Venogenic impotence following
152 Alman BA, Greel DA, Ruby LK, Goldberg MJ, Wolfe HJ.
dermal graft repair for Peyronie’s disease. J Urol 1991;146:
Regulation of proliferation and platelet-derived growth factor
expression in palmar ﬁbromatosis (Dupuytren contracture)
174 Gelbard MK. Relaxing incisions in the correction of penile
by mechanical strain. J Orthop Res 1996;14:722–8, 38.
deformity due to Peyronie’s disease. J Urol 1995;154:1457–
153 Brighton CT, Fisher JRS Jr, Levine SE, Corsetti JR, Reilly T,
Landsman AS, Williams JL, Thibault LE. The biochemical
175 Kovac JR, Brock GB. Surgical outcomes and patient satisfac-
pathway mediating the proliferative response of bone cells to a
tion after dermal, pericardial, and small intestinal submucosal
mechanical stimulus. J Bone Joint Surg Am 1996;78:1337–47.
grafting for Peyronie’s disease. J Sex Med 2007;4:1500–8.
154 Levine LA, Newell M, Taylor FL. Penile traction therapy for
176 Leungwattanakij S, Bivalacque TJ, Reddy S, Hellstrom WJ.
treatment of Peyronie’s disease: A single-center pilot study. J
Long-term follow-up on use of pericardial graft in the surgi-
cal management of Peyronie’s disease. Int J Impot Res
155 Gontero P, Di Marco M, Giubilei G, Bartoletti R, Pappagallo
G, Tizzani A, Mondaini N. Use of penile extender device in
177 Choi JM, Alex B, Mulhall J. Erectile dysfunction after plaque
the treatment of penile curvature as a result of peyronie’s
incision and grafting: Incidence and predictors. Abstract 730.
disease. Results of a phase ii prospective study. J Sex Med
Annual Meeting of the American Urological Association;
156 Kendirci M, Hellstrom WJ. Critical analysis of surgery for
178 Kadioglu A, Sanli O, Akman T, Ersay A, Guven S, Mamma-
Peyronie’s disease. Curr Opin Urol 2004;6:381–8.
dov F. Graft materials in Peyronie’s disease surgery: A com-
157 Taylor FL, Levine LA. Surgical correction of Peyronie’s
prehensive review. J Sex Med 2007;4:581–95.
disease using Tunica albuginea plication or partial plaque
179 Brannigan RE, Kim ED, Oyasu R, McVary KT. Comparison
excision with pericardial graft: Long-term followup. J Sex
of tunica albuginea substitute for the treatment of Peyronie’s
180 Edygio PH, Lucon AM, Arap S. Treatment of Peyronie’s
186 Breyer BN, Brant WO, Garcia MM, Bella AJ, Lue TF. Com-
disease by incomplete circumferential incession of the tunica
plications of porcine small intestine submucosa graft for Pey-
albuginea and plaque with bovine pericardium graft. Urology
ronie’s disease. J Urol 2007;177:589–91.
187 Hsu GL, Chen HS, Hsieh CH, Chen RM, Wen HS, Liu LJ,
181 Moncata-Iribarren I, Jara J, Martinez-Salamanca JI, Cabello
Chua C. Long-term results of autologous venous grafts for
R, Hernandez C. Managing penile shortening after Peyro-
penile morphological reconstruction. J Androl 2007;28:186–
nie’s disease surgery: A comprehensive review. J Sex Med
2007;177(suppl 4):252; abstract 750.
188 Kalsi J, Minhas S, Christopher N, Ralph D. The results of
182 Knoll LD. Use of small intestinal submucosa graft for the
plaque incision and venous grafting (Lue procedure) to
surgical management of Peyronie’s disease. J Urol 2007;178:
correct the penile deformity of Peyronie’s disease. BJU Int
183 Hatzichristou DG, Hatzimouratidis K, Apostolidis A,
189 Montorsi F, Salonia A, Briganti A, Dehò F, Zanni G,
Tzortzis V, Bekos A, Ioannidis E. Corporoplasty using tunica
Luigi DP, Rigatti P. Five year follow up of plaque incision
albuginea free grafts of penile curvature: Surgical technique
and vein grafting for Peyronie’s disease. Abstract 1256.
and longterm results. J Urol 2002;167:1367–70.
Annual Meeting of the American Urological Association;
184 Lue TF, El-Sakka AI. Venous patch graft for Peyronie’s
disease. Part I: Technique. J Urol 1998;160:2047–9.
190 Wilson SK. Delk 2nd JR. A new treatment for Peyronie’s
185 Levine LA, Estrada CR. Human cadaveric pericardial graft
disease: Modeling the penis over an inﬂatable penile proth-
for the surgical correction of Peyronie’s disease. J Urol
Site sponsored by Safe Harbor, a nonprofit corporation President, Institute for Optimum Nutrition (ION) Food and Mood Poster T-Shirts, Bumper Stickers Janet was diagnosed with manic depression at the age of 15. At times she would become completely hyperactive and manic, and at other times become completely depressed. She was put on three drugs - Lithium, Tegretol and
FEBRUARY 5 6 7 8 9 10 11 12 13 14 15 16 17 18 9 10 11 12 13 14 15 9 10 11 12 13 14 15 21 22 23 24 25 18 19 20 21 22 18 19 20 21 22 26 27 28 29 30 31 23 24 25 26 27 28 23 24 25 26 27 28 29 6 7 8 9 10 11 12 4 5 6 7 8 9 10 8 9 10 11 12 13 14 13 14 15 16 17 18 19 11 12 13 14 15 16 17 18 19 20 21 20 21 22 23 24 25 2