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Non-invasive treatment in the management of Peyronie’s disease



Peyronies disease (PD) is estimated to affect approximately 3–9% of men worldwide and maybe associated with pain, erectile dysfunction and penile deformity including shortening. The condition has significant debilitating effects on quality of life, self-esteem and psychological wellbeing in addition to sexual function. Surgical results add further to this by patients having dissatisfaction with various aspects of outcomes. Non-surgical management may allow patients to avoid the morbidities associated with surgery and still achieve improved functional and aesthetic outcomes. Several non-surgical options are currently being employed in the treatment of PD that may reduce or stabilize both objective measures (e.g. penile length and deformity) and subjective measures (including sexual function, pain and partner satisfaction). Nonsurgical management can allow patients to avoid the morbidities associated with surgery and still achieve improved functional and aesthetic outcomes. In this article we explore the current non-surgical management options for PD including oral, mechanical therapies, intralesional and topical treatments. We also briefly discuss future treatment options in the form of stem cell therapy.
Ther Adv Urol
2019, Vol. 11: 1–13
DOI: 10.1177/
© The Author(s), 2019.
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Therapeutic Advances in Urology 1
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Peyronie’s disease (PD) is characterized by a
fibrous, inelastic lesion of the tunica albuginea. It
is estimated to affect approximately 3–9% of men
worldwide, although this figure may be higher in
high-risk subgroups, for example, diabetes.1–3
The disease maybe associated with pain, erectile
dysfunction, and penile deformity, including
shortening. The condition has significant debili-
tating effects on quality of life, self-esteem and
psychological wellbeing in addition to sexual
Approximately 48% of men with PD suffer from
depression (26% moderate, 22% severe) with
81% reporting emotional distress related to PD.5,6
These psychological effects are mostly due to
changes in physical appearance and self-image
induced by penile deformity. The resultant effects
include reducing the quality and frequency of sex-
ual relationships, reducing libido and intimacy,
and resultant social and personal difficulties for
relationships.5,7,8 A qualitative study of the psy-
chosocial outcomes for patients with PD identi-
fied four core domains important to men including
physical appearance and self-image, sexual func-
tion and performance, PD-related pain and dis-
comfort and social stigmatization and isolation.8
Other themes highlighted include loss of sexual
confidence and feelings of attractiveness, perfor-
mance anxiety and concern about not satisfying
partners sexually.8
Relationship stress was also reported with 54% of
men reporting that PD had negatively impacted
their relationship, demonstrating that the burden
of the disease is shared by both patients and their
partners.9–11 Partners of men with PD were found
to have decreased sexual function, sexual satisfac-
tion, and mood compared with population-based
norms.12 Preliminary research has also shown neg-
ative partner reactions to be associated with lower
sexual and relationship satisfaction in men with
PD.13 Assessment of the emotional, psychosexual,
Non-invasive treatment in the
management of Peyronie’s disease
Karen Randhawa and C. J. Shukla
Peyronies disease (PD) is estimated to affect approximately 3–9% of men worldwide
and maybe associated with pain, erectile dysfunction and penile deformity including shortening.
The condition has significant debilitating effects on quality of life, self-esteem and psychological
wellbeing in addition to sexual function. Surgical results add further to this by patients having
dissatisfaction with various aspects of outcomes. Non-surgical management may allow patients
to avoid the morbidities associated with surgery and still achieve improved functional and
aesthetic outcomes. Several non-surgical options are currently being employed in the treatment
of PD that may reduce or stabilize both objective measures (e.g. penile length and deformity)
and subjective measures (including sexual function, pain and partner satisfaction). Nonsurgical
management can allow patients to avoid the morbidities associated with surgery and still achieve
improved functional and aesthetic outcomes. In this article we explore the current non-surgical
management options for PD including oral, mechanical therapies, intralesional and topical
treatments. We also briefly discuss future treatment options in the form of stem cell therapy.
Peyronie’s disease, collagenase, intralesional injections, mechanical penile
therapies, stem cell therapy
Received: 25 July 2018; revised manuscript accepted: 5 December 2018.
Correspondence to:
C. J. Shukla
Western General Hospital,
Crewe Road South,
Edinburgh, EH4 2XU, UK
Karen Randhawa
Western General Hospital,
Edinburgh, UK
823671TAU0010.1177/1756287218823671Therapeutic Advances in UrologyK Randhawa and C J Shukla
Therapeutic Advances in Urology 11
and relationship aspects of the patient’s PD symp-
toms that negatively impact the patient’s quality of
life, are needed to prioritize treatment goals.14
Despite multiple treatment options, PD remains a
therapeutic dilemma due to an incomplete under-
standing of its aetiology, and the relative paucity of
larger multi-institutional series and randomized,
placebo-controlled trials.15 The pathophysiology is
multifactorial in origin and is believed to occur as a
result of aberrant penile wound healing in geneti-
cally susceptible individuals, who experience a
localized response to endogenous factors [trans-
forming growth factor beta (TGF-β)] released in
response to microtrauma. This inflammatory
response leads to the formation of fibrous inelastic
plaque(s) within the bilayer of the tunica albug-
inea.16,17 The exact aetiology is unknown.
Nonsurgical treatment modalities to date have
focused on disrupting these processes.
Surgical options are suitable in correcting the
deformity and aiding the ability to resume sexual
function. However, they leave the patient with dis-
satisfaction due to loss of length of the phallus,
residual deformity or erectile dysfunction necessi-
tating the use of treatment.18–20 Evidence suggests
that more than 65% of patients experience dissatis-
faction following Lue’s procedures for PD.21
Additionally, satisfaction following penile prosthesis
surgery for PD is lower than with the general popu-
lation receiving the implant for other reasons, for
example, vasculogenic or diabetic erectile dysfunc-
tion.20 The psychological effects of available surgical
treatments and possible complications should all be
taken into account when counselling patients
regarding treatment options. Several nonsurgical
options are currently being employed in the treat-
ment of PD that may reduce or stabilize both objec-
tive measures (e.g. penile length and deformity) and
subjective measures (including sexual function,
pain and partner satisfaction).22 Nonsurgical man-
agement can allow patients to avoid the morbidities
associated with surgery and still achieve improved
functional and aesthetic outcomes.
Course of Peyronie’s disease
There are two distinct phases of the disease; with
the acute or active phase being characterized by
active inflammation, penile pain and evolving
deformity of the erect penis.23 The pain usually
resolves by 12–18 months in 90% of men. After
this phase, the vast majority of patients will pro-
gress on to stabilization of the plaque or
progression of their disease. Approximately
3–13% of men describe spontaneous improve-
ment,24 however, 30–50% of men will have pro-
gressive deterioration. The optimal time for
nonsurgical intervention is likely during the active
phase, when the inflammation is treatable.25 The
chronic phase is characterized by stable curva-
ture, pain resolution and the palpation of a hard,
palpable plaque, although a plaque may not be
present in all patients. Fibrosis, dystrophic calcifi-
cations and rarely ossification may occur in this
Management options
Management options include mechanical, oral,
intralesional and topical therapies. The nonsurgi-
cal management options with the most compel-
ling contemporaneous evidence to support their
use in PD are intralesional collagenase Clostridium
histolyticum (CCH) and mechanical penile thera-
pies, which may be used individually or in con-
junction with one another.
Intralesional CCH
CCH consists of purified enzymes (Auxilium [AUX]
I and II) produced by the bacterium C. histolyticum.
The collagen types I and III targeted by CCH are
the most abundant fibres found in the plaques of
Peyronie’s patients. When CCH is administered
intralesionally, it cleaves type I and III collagens in a
synergistic manner.27 CCH has also been shown to
directly induce apoptosis in fibroblasts and decrease
the expression of smooth muscle actin, transforming
growth factor-β1 and fibronectin.28
CCH is the only drug approved by the US Food and
Drug Administration (FDA) in 2013 for treatment of
PD in men with dorsal or lateral penile curvature
greater than 30° with or without a noncalcified penile
plaque.27 It has also been approved in 2014 by the
European Medicines Agency.
Initial studies have demonstrated its safety in ran-
domized, placebo-controlled double-blind phase
IIa trials which have also shown statistically sig-
nificant improvement in penile curvature at an
optimal dosage of 0.58mg.29,30 Subsequent stud-
ies have also tested the therapeutic effects seen
with different treatment regimes with and without
the use of modelling.31
Two large randomized double-blinded, placebo-
controlled phase III trials in the US and Australia
K Randhawa and C J Shukla 3
(IMPRESS I and II) have confirmed its efficacy.
Each participant underwent up to four treatment
cycles (consisting of two injections of either CCH
0.58 mg or placebo) 6 weeks apart, with approxi-
mately 24–72 h between injections. After the second
injection of each cycle, patients underwent penile
plaque modelling performed by the investigator,
after which they were then instructed to perform
home penile modelling three times per day during
the 6-week period in between each treatment cycle.32
Patients treated with CCH showed a statistically
significant improvement in penile curvature com-
pared with those receiving placebo (34% versus
18.2% respectively) and significant improvement
in Peyronie’s disease questionnaire (PDQ) bother
score compared with placebo. Changes in penile
plaque consistency were reported, in addition to
improvement noted on International Index of
Erectile Function (IIEF) overall satisfaction and
PDQ psychological symptom score. These results
have also been replicated in other phase III trials.33
Most common treatment-related adverse events
(AEs) observed were mild to moderate in severity
and were mostly localized to the injection area.
The most frequently reported AEs (45% or
greater) in CCH-treated men included penile
ecchymosis, penile swelling and penile pain.32 Six
patients experienced treatment-related serious
AEs including three corporeal ruptures and three
penile haematomas. All three corporeal ruptures
and one penile haematoma required surgical
repair, although the incidence of this may be higher
and may not require surgical intervention based on
a survey by the Sexual Medical Society of North
America (SMSNA).32,34 The senior author CJS
himself does not use any compressive dressing,
and any bruising/oedema, etc. usually resolves by
the end of 1 week following treatment and is mild
enough to target a second injection into the plaque.
The SMSNA Survey34 found that 37% of respond-
ers also recommended no dressing following injec-
tion. Interestingly, this survey also showed no
increase of haematoma incidence was detected in
patients in whom penile dressing was not applied
and in anticoagulant- or platelet-using patients.
The International Consultation on Sexual
Medicine (ICSM) guidelines15 recommend that
the use of collagenase should be restricted to those
with a stable curvature greater than 30° and less
than 90°, no isolated hourglass deformity, calcified
plaque or proximally located plaque at the base of
the penis, with normal erectile function (grade B,
level 2). As clinical trials have not evaluated the use
of collagenase in patients with ventral curvature,
calcified plaques, hourglass deformity or plaque
located proximal to the base of the penis, it is
uncertain as to whether these effects could be rep-
licated in all PD patients.
The use of collagenase within the acute phase is
also currently being assessed in trials where a
mean curvature decrease of 20° after treatment
was seen compared with 13.9° curvature seen in
patients with chronic disease.35 There are limita-
tions to this analysis based on the small number of
patients in this trial, however early intervention
during the acute phase could decrease penile
deformity, the degree of penile fibrosis and subse-
quently decrease pain and sexual dysfunction.36
To date, clinical trials have not evaluated CCH
use in ventral plaques, due to previous concerns
of urethral injury during penile modelling.37
Mechanical penile therapies
Penile traction therapy (PTT)
The role of traction therapy in PD is to stop the
progression of scarring, recover penile length and
girth, reduce curvature, enhance sexual function
and ultimately to avoid or simplify surgery.38
Application of mechanical stress modulates cell
function through mechanotransduction, a cellu-
lar process that translates mechanical stimuli into
a chemical response leading to activation of cell
proliferation. Traction devices decrease myofi-
broblast activity and lead to upregulation of
matrix metalloproteinases.39
European Association of Urology (EAU) guide-
lines state that ‘PTT may reduce penile deform-
ity and increase penile length.’40 Preliminary
studies have revealed that its regular use maybe
associated with reduction in penile curvature,
increase in flaccid penile length and improve-
ment in penile pain.41,42
A recent nonrandomized, controlled trial assessed
the use of penile traction in the acute phase of
PD, assessing not only the impact on curvature,
length and sexual function, but also correlation
with sonographic penile evaluation. This trial
showed a mean improvement in penile curvature
of 20°, decreased pain and improved sexual func-
tion, in addition to disappearance of sonographic
plaques in 48% of patients. The need for surgery
Therapeutic Advances in Urology 11
was reduced in 40% of patients who would other-
wise have been candidates for surgery. Predictors
of success were penile curvature < 45% at base-
line, time from diagnosis < 3 months, absence of
plaque on the ultrasound study, age < 45 years
and Visual Analogue Scale score for penile
pain > 5.43
This study recommended the duration of PTT
should not be shorter than 6 months, and must be
worn at least 6 h a day to obtain these results. The
therapy therefore requires a committed and com-
pliant patient who is willing to devote time to a
relatively long treatment period. PTT is, how-
ever, a tolerable minimally invasive method for
men with PD.44
Studies are currently in process to help design an
optimal protocol, assess efficacy of the different
devices available and which men are most likely
to benefit from their use. Further prospective,
randomized, controlled studies with a larger
number of patients and longer follow-up periods
are needed. The ICSM guidelines support this,
stating there may be some benefit in its use in PD
patients (grade C, level 3).
Furthermore, the use of PTT concomitantly with
either verapamil or interferon (IFN) α2b has also
been shown an effective therapy.45 A study per-
formed investigating the benefit of PTT with
intralesional verapamil, oral L-arginine and pen-
toxifylline showed better curvature improvement
and stretched penile length gain seen in the combi-
nation group. Additionally, length improvement
was related to the duration of traction device use.
Daily PTT was assessed in men with PD who also
underwent IFN α2b, however this study showed
that PTT did not change penile girth. An impor-
tant finding was that the use of PTT for 3 h or
more resulted in a significant increase in stretched
penile length of 0.31 cm compared with the use of
PTT for less than 3 h.46
Combined use of PTT with collagenase Clostridium
histolyticum. One study has been performed to
evaluate the impact of combined use of PTT with
CCH.47 Utilization patterns, attrition, and com-
pliance issues were noted to be relevant factors
impacting efficacy. PTT use declined in both fre-
quency and duration with subsequent injection
series. Overall, men treated with CCH exhibited
significant decreases in penile curvature, consis-
tent with the phase III trials (IMPRESS). When
stratified by PTT, no statistically significant dif-
ferences were identified in mean penile curvature
improvement or stretched penile length, although
only a minority of patients in the PTT arm were
actually compliant with the therapy.
Further studies are currently being carried out to
assess the optimal protocol; with a recently pub-
lished study adopting three intralesional injections
of CCH (0.9 mg) given at 4-weekly intervals using
a new modified injection technique in an attempt to
reduce cost and number of patient visits. A sum of
95.5 of patients in this study had an improvement
in curvature with a mean value of 17.08° (0–40°) or
30.8% from baseline (0–57%) after three injec-
tions.48 One retrospective study has also assessed
the relation between the number of treatment
cycles and clinical outcomes for patients treated
with CCH. Penile curvature was found to improve
significantly after the first three treatment cycles
but not the fourth, suggesting that further trials
with fewer cycles may need further consideration.
This trial also showed that patients who have a
strong response to the first cycle of CCH are more
likely to have a superior final decrease in penile cur-
vature after completion of treatment cycles.49
A recent study has evaluated patient and partner
satisfaction following CCH, showing 67% part-
ner and 71% female sexual partner satisfaction
with treatment respectively and is correlated with
recall of prior penile trauma, improved ability to
have sexual intercourse, and absence of post-pro-
cedural glans hypoesthesia.50 Goldstein and col-
leagues similarly had the same findings in their
study based on 30 female partners of patients who
had undergone CCH therapy.51
Vacuum erection device
The role of vacuum erection device (VED) as a
treatment for PD is less well established than
PTT. Basic science studies suggest that VED
results in dilation of cavernous sinuses, retrograde
venous blood flow, and increased arterial
inflow.52,53 The additional penile blood supply
enhances cavernosal tissue oxygenation that sub-
sequently leads to decreases in hypoxia-inducible
factor-1a, TGF-β1, collagenase. This leads to
increases in endothelial nitric oxide synthase and
α-smooth muscle actin.54 When comparing the
impact of VED and PTT in a rat model of PD,
results showed enhanced preservation of α-
smooth muscle actin and decreased TGF-β1 with
VED versus PTT. The underlying mechanism
K Randhawa and C J Shukla 5
could be related to antiapoptosis, antifibrosis, and
smooth muscle preservation.55 There is, however,
limited evidence establishing the effect of VED in
different phases of PD.
The clinical evidence for its efficacy is based on
one single-arm observational study by Raheem
and colleagues on 31 patients using the device for
20 min per day.56 They noted that two thirds of
their patients had a modest improvement of
between 5–25°, with 10% having a worsening of
their curvature and 23% experiencing no change.
Their primary endpoint was a change in curva-
ture, but not how many patients avoided surgery
from this intervention.
Consensus statements on VED from the ICSM in
2015 suggested that, with the limited data availa-
ble in PD, it could have a role as a primary treat-
ment or postoperatively after incision or excision
and grafting surgery.15
VED combined with CCH. Raheem and col-
leagues48 evaluated a shortened modified proto-
col of CCH in combination with VED showing an
equal efficacy across all categories of curvatures
as compared with the IMPRESS trials. This
requires 4 instead of 14 visits, over 12 instead of
24 weeks. It remains to be seen in future trials
whether VED is more efficacious with CCH as
opposed to either treatment alone.
The remaining nonsurgical options can be divided
by various delivery modalities into oral therapies,
intralesional, and topical therapies.
Oral therapies
Although oral treatments are an attractive option
due to the ease of delivery, the evidence of out-
comes from published series has proved disap-
pointing. As a result, many international guidelines
advise only limited use of these therapies based on
the low level of evidence. The EAU guidelines state
that oral treatment with potassium para-aminoben-
zoate may result in a significant reduction in penile
plaque size and penile pain, as well as penile curva-
ture stabilization with level 1b evidence.40
The published literature shows minimal or no
benefit regarding the use of other oral therapies
(e.g. vitamin E, colchicine, pentoxifylline) to sig-
nificantly improve the penile deformity in PD;
therefore, they are not recommended in the
ICSM guidelines.15
Intralesional injections
Intralesional injections, specifically IFN α2b,
verapamil and CCH have proved more effective
than topical and oral medications in the treat-
ment of PD.
Corticosteroids have been employed in PD due to
their anti-inflammatory effects since the 1950s.
Initial studies showed some objective improve-
ment in penile curvature, however similar find-
ings were also seen in the placebo groups.57–62
This raised the possibility that observed therapeu-
tic effects seen with intralesional steroid injection
were likely related to the mechanical effect of the
injection rather than the drug on PD remodelling.
Unfavourable side effects (wound infection, local
tissue atrophy and fibrosis) coupled with limited
efficacy do not support its use.
Intralesional injection verapamil
The use of intralesional verapamil in PD was
introduced in the mid 1990s, with initial studies
showing an improvement in penile curvature and
plaque volume using a biweekly series of injec-
tions, with several modifications to treatment
regimens since.63–67
The rationale for intralesional use of verapamil (a
calcium-channel antagonist) in patients with PD
is based on in vitro research showing interference
with fibroblast cellular proliferation.68,69 In ani-
mal models, histological evidence of cellular
changes of decreased collagen and elastin fibres
were seen, with improvement in penile pressures
also noted.70
Intralesional verapamil has been evaluated in
multiple randomized studies, including most
recently, comparisons with tadalafil,71 hyaluronic
acid,72 and thiocolchicine.73 In a trial comparing
its use with tadalafil, intralesional verapamil did
not improve plaque size or curvature degree with
a mean baseline curvature of 20° in all groups
with no statistically significant improvement in
curvature.73 This was also confirmed in a pro-
spective, double-arm, randomized, double-
blinded study that showed no improvement in
penile curvature with verapamil, although this
concluded a greater efficacy of hyaluronic acid in
terms of penile curvature and patient satisfaction
in over 100 patients when compared with vera-
pamil. However, the mean baseline curvature was
Therapeutic Advances in Urology 11
33°, with change following treatment deemed as
between 0° and 4° decrease in curvature.71
Intralesional thiocolchicine, achieved similar
results to verapamil, with improvement in curva-
ture reported in 69% of cases treated with thio-
colchicine and in 66% of those who received
verapamil. However, the study was limited due to
its small size (only 25 patients) and the improve-
ment in curvature which was not deemed statisti-
cally significant with either treatment.73
Comparisons among previously published non-
controlled, single-arm, prospective clinical trials
on intralesional verapamil injections have shown
a greater decrease in penile curvature after pro-
longed treatment with 12 injections over 6 months
compared with 6 injections over 3 months.74,75
It appears that the injected volume, frequency, con-
centration, and duration of the injection protocol
affects outcome results. Longer treatment periods
of concentrated intralesional verapamil in younger
men with small plaques but large curvature have
been shown to receive the optimal benefit.76,77
Overall, the evidence suggests that intralesional
verapamil injections could be advocated for the
treatment of noncalcified acute phase or chronic
plaques to stabilise disease progression or reduce
penile curvature, although no optimal treatment
regime exists at present. The ICSM guidelines
support that intralesional verapamil has shown
some outcome benefits in PD management15
(grade C, level 3).
Common reported AEs include penile bruising,
swelling, and pain at the injection site, however,
dizziness, nausea, sweating and loss of libido have
also been reported in rare cases.78
Intralesional interferon α2b
IFN α2b has been shown to decrease extracellu-
lar matrix production, inhibit fibroblast prolifera-
tion, and therefore decrease collagen production
from fibroblasts and improve the wound healing
process from PD plaques in vitro.79,80 Evidence
also suggests that IFN leads to an improvement
in penile haemodynamics, thereby improving
erectile function.81,82
A double-blind, placebo-controlled trial80 showed
that intralesional IFN α2b, when injected biweekly
for 12 weeks, led to a modest but significant
improvement in penile curvature (13° versus 4° in
the placebo arm), decreased pain relief and plaque
size. A more recent study also supported these
findings, demonstrating a statistically significant
improvement in curvature with intralesional IFN
α2b, without affecting vascular parameters.83 The
absolute improvement in curvature was found to
be independent of pretreatment curvature or dura-
tion of disease. Recent evidence has also shown
this improvement to be independent of plaque
location with a >20% reduction in curvature seen
in the majority of men with PD when treated with
intralesional IFN α2b.84
IFN α2b injections have a good safety profile,
with the most common AEs being self-limiting
flu-like symptoms.
The ICSM guidelines state that intralesional IFN
has shown some outcome benefits in PD manage-
ment15 (grade B, level 2).
Hyaluronic Acid (HA)
Intralesional HA decreases inflammatory
cytokines, and thereby reduces inflammation and
scar formation. This is a relatively novel treat-
ment that appears to have some efficacy in
improving symptoms, however data comparing
HA treatment with placebo or alternative thera-
pies are lacking.
In one recent study, 81 patients in the active
phase of the disease underwent a 10-week cycle of
weekly plaque injections.85 HA demonstrated sta-
tistically significant improvement over controls in
plaque size, penile curvature and improvement in
penile rigidity at 12 months. Improvements
remained stable at 24 months.
In a prospective, single-arm, multicentre pilot
study, 65 patients underwent a 10-week cycle of
weekly intralesional injections with HA. This study
showed a significant decrease in plaque size, and
decreased penile curvature in 37% with improve-
ment in overall sexual satisfaction.86 These findings
were also confirmed in a prospective, double-arm,
randomized, double-blinded study showing greater
efficacy of HA in terms of penile curvature and
patient satisfaction compared with intralesional
verapamil.72 Although plaque size and overall sex-
ual satisfaction improved with both therapies, bet-
ter outcomes were observed in patients treated with
HA, although not deemed statistically significant.
Further prospective, randomized controlled trials
K Randhawa and C J Shukla 7
(RCTs) will need to be performed prior to bring
about the routine recommendation of HA.
HA has a lower risk of adverse effects compared
with other molecules used ‘off label’ for intrale-
sional therapy. Its use is also being evaluated in
electromotive administration comparing the
effects with verapamil. However, although HA
proved to be more efficient than verapamil in
both reducing curvature, pain and plaque area,
and in improving erectile function, this was not of
statistical significance and was evaluated in
patients with curvature < 30°.
Plasma-rich platelets (PRP) + Hyaluronic Acid
PRP injections have been used to improve angi-
ogenesis and wound healing, and could theo-
retically improve ED, PD and stress urinary
PRP is derived from the centrifugation of whole
blood with a separator gel to remove the red and
white blood cells. The resulting supernatant has a
greater-than-fourfold increase in platelets and
other plasma proteins.89 This concentrate is then
administered via injection into the lesion com-
bined with HA.
There have been limited trials into its use to date,
mainly by Virag etal.90 In a recent trial, 90 patients
were injected intralesionally under ultrasound
guidance with four to eight sessions applied at
15-day intervals for the first four and monthly
thereafter.90 Changes in PDQ, IIEF-5, angula-
tion and maximum thickness were evaluated 1
month after the last session. Average angulations
(curvature or deformation) were reduced by
39.65%; with the mean final improvement 16.54
± 10.51°. The average maximum thickness
diminished by 1.1 mm, with the average PDQ
score decreased by 5.5. IIEF-5 improved signifi-
cantly, with 43.3% judging that their erections
were better and 46.7% perceiving that sexual
activity was easier following the treatment.
Superficial haematomas were observed in 10% of
the injection sites with ecchymosis present in
16.7% of patients.
PRP with HA has been demonstrated efficiency
in 70%, without any severe complication. If con-
firmed in additional and larger series, PRP with
HA could be adopted as a cost-effective mini-
mally invasive treatment of PD.
Topical therapies
Topical verapamil is not recommended in
Peyronie’s patients15 (ICSM guidelines grade B,
level 3). These recommendations are based on a
study where men who were pretreated with topical
verapamil then immediately underwent surgical
correction for their PD.91 These excised samples
(mean 1.1 g) of tunica failed to show the presence
of any verapamil, demonstrating that the gel does
not infiltrate the tunica albuginea.
Electromotive drug administration/
Iontophoresis involves the transport of ions
through tissue by means of an electric current,
causing electrokinetic repulsion of positively
charged medication toward the diseased target
tissue, limiting systemic side effects.92 It is also
thought to provide superior tissue penetration for
the transdermal application of medications.22
Excised Peyronie’s plaques following electromo-
tive drug therapy with dexamethasone, verapamil
and lidocaine have been shown to have decreased
expression of basic fibroblast growth factor.93
Despite initial trials showing promising results on
plaque size, curvature and pain using a variety of
different pharmacologic agents over the course of
short, three-week treatment regimes, a subse-
quent RCT demonstrated that there was no supe-
riority of the use of verapamil alone compared
with saline placebo.94–96
A recent study compared the administration of
combination therapy of verapamil and dexametha-
sone administered via electromotive drug adminis-
tration (EMDA) with intralesional administration;
although EMDA administration showed improve-
ments with regards to plaque length, plaque width,
penile curvature, plaque volume and erectile dys-
function, these were not statistically significant.
The ICSM guidelines have therefore not recom-
mended the use of iontophoresis in PD patients
(grade B, level 3). 15
Topical H-100 gel
H-100 gel combines a natural carrier agent, emu
oil, with nicardipine and superoxide dismutase.
Emu oil has an anti-inflammatory effect, demon-
strated in animal studies and, when applied topi-
cally, decreases the levels of pro-inflammatory
cytokines in tissue and therefore inhibits local
Therapeutic Advances in Urology 11
secondary inflammation to promote wound
healing.97,98 In a double-blind, placebo-con-
trolled pilot study designed to assess safety, 22
patients in the acute phase of PD were rand-
omized to receive 3 months of either placebo or
H-100 gel to be applied focused on the plaque,
but to also cover the entire shaft. Following these
3 months, all study participants received H-100
gel for a further 3 months.99
In the treatment group, significant reductions in
penile curvature and pain level were seen, as well as
an increase in penile length. The drug was well tol-
erated overall, with a self-limiting skin rash as the
only adverse event. Although this trial was designed
to assess safety, its initial positive outcomes make it
an encouraging novel treatment although more effi-
cacy and safety data from larger trials are required
prior to recommendation for usage.100
Low-intensity extracorporeal shockwave
Local penile low-intensity extracorporeal shock-
wave therapy (Li-ESWT) has been used to treat
PD with mixed results. The hypotheses behind its
mode of action include direct damage to the
plaque, resulting in an inflammatory reaction
with increased macrophage activity leading to
plaque lysis, improved vascularity resulting in
plaque resorption, and the creation of contralat-
eral scarring of the penis resulting in ‘false’
Most uncontrolled studies have failed to show
any significant improvements in patients with
PD.102–104 Increasing evidence suggests that
Li-ESWT has minimal impact on deformity cor-
rection but provides a more rapid decrease of
pain and stabilization of curvature in patients
with PD (grade B, level 3).15,105,106 The treatment
may not be recommended, as pain may resolve
spontaneously in the natural history of disease
and the deviation may worsen with ESWT. Its
potential side effects, including penile fibrosis and
development of erectile dysfunction, have pre-
cluded its widespread use.107,108
Overall, the published literature has largely failed
to demonstrate any significant benefit in treating
penile curvature, however outcomes are inter-
preted with caution due to methodological flaws.
There is anticipation of future studies clarifying
ESWTs role in PD curvature improvement/reso-
lution more clearly.
Stem-cell therapy/Regenerative medicinal
There is now increasing evidence for the role of
mesenchymal stem cells (MSCs) as a potential
treatment for fibrosis in PD. These cells originate
from fetal tissue, umbilical cord blood, or adult tis-
sues and may also exert beneficial effects promot-
ing local growth, repair, and regeneration of the
tissue in which they reside.109–111
Studies involving rat models have been performed
to determine the effects of stem-cell treatment in
PD.112,113 Injection of adipose tissue–derived stem
cells (ADSC) into the tunica albuginea in rat mod-
els during the acute phase of PD prevented forma-
tion of fibrosis in the tunica and corpus cavernosum
and statistically significantly improved erectile
function.112 Another study demonstrated that
ADSCs combined with IFN α2β injections pre-
vented or reduced Peyronie’s plaques by decreas-
ing the expression of tissue inhibitors of
metalloproteinases.113 They showed that ADSCs,
both alone and in combination with IFN, resulted
in improved erectile response and decreased
PD-like manifestations in a PD rat model.
To date, there have been very few studies per-
formed in humans.114 In one prospective study,
patients with PD were injected with PM-MSCs
(placental-matrix-derived mesenchymal stem cells)
and followed up to assess changes in plaque vol-
ume, penile curvature, and erectile function.114 Of
a total of 10 plaques managed, 7 had disappeared
completely at 3-month follow up. Changes in end-
diastolic velocity, stretched penile length and penile
girth were not statistically significant. Both penile
curvature and peak systolic velocity were signifi-
cantly improved at 6 weeks, 3 months, and 6
months after PM-MSC injection, but end diastolic
volume (EDV) did not prove to demonstrate a sta-
tistically significant improvement. The results sug-
gest that PM-MSCs may be beneficial and effective
as a nonsurgical treatment in PD patients.
It seems evident in experimental settings that stem
cells in general (ADSCs in particular) provide a
feasible, safe and effective therapy for PD.114
However, further prospective human studies are
needed to further elucidate the therapeutic poten-
tial of stem-cell therapy in PD.
Oral therapies serve a very limited role in treat-
ment due to their limited efficacy and are not
K Randhawa and C J Shukla 9
currently recommended for use.15 Mechanical
therapies and vacuum extender devices have been
shown to provide some benefit, although they
require daily use and a motivated patient to con-
tinue long-term use.
Intralesional CCH is the first FDA-approved
medication and can be considered a reasonable
alternative to surgery for patients desiring con-
servative treatment, based on its improvement in
penile curvature and symptom bother. Alternative
intralesional therapies are promising, however
additional large studies are needed to evaluate
their efficacy prior to recommendations regarding
their use. Topical treatments (for example vera-
pamil and iontophoresis) also have mixed results
based on the published literature and are not cur-
rently recommended for use.15 Currently, it is
likely, in the context of nonsurgical treatments,
that a multimodal approach, for example, combi-
nation of mechanical therapies and CCH, is the
most suitable way forward in managing this
Although stem-cell therapy offers a promising
potential future treatment, it is still in the experi-
mental phase with paucity of data supporting its
use and long-term effects at present.
Important advances in the physical treatment of
penile curvature in PD do not however negate the
need for the development and examination of effec-
tive educational, psychological, and psychosexual
interventions to address unmet needs in PD.115
This research received no specific grant from any
funding agency in the public, commercial, or not-
for-profit sectors.
Conflict of interest statement
The authors declare that there is no conflict of
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... Historically, intralesional injections such as steroids, verapamil, IFN alpha-2b, Onabotulinumtoxin A, or Botox (AbbVie, Chicago, Illinois), among others and have proved effective when topical or oral medications fail for treatment of PD. 3 Intralesional dexamethasone was reportedly used in the 1950s with reduction in plaque size and penile pain. While the significance of improvement remains unclear, this modality quickly fell out of favor as prolonged use resulted in local tissue atrophy over the penile skin. ...
... In 2013, CCH became the only form of intralesional injection therapy approved by the US Food and Drug Administration (FDA) for the treatment of Peyronie's disease in men with dorsal or lateral penile curvature greater than 30° with or without a noncalcified plaque. 3 CCH was also approved by the European Medicines Agency for the treatment of PD in 2014. Criteria for the Approval of CCH as defined by the FDA are found in Table 1. ...
Full-text available
Purpose: In this narrative review we explore additional indications for which intralesional collagenase Clostridium histolyticum (CCH) injection therapy may be used, in addition to those utilized in the IMPRESS trials. The goal is to provide updated assessment of available intralesional therapies and justify whether to expand clinical indications based on advancements over the last decade. Results: Patients receiving CCH in the acute phase of PD have shown significant improvement in penile curvature - which may be even more significant than reported due to progressive curvature over the longitudinal course of injection therapy. Across studies, patients with ventral plaques achieved the greatest curvature improvement (~30°) compared to PD patients with dorsal or lateral plaques. Patients with curvature > 90° have been minimally documented. However, the concept of patients with higher degree of curvature achieving more significant degrees of improvement prevails across studies. Studies including PD patients with volume loss deformities or indentation(s) focus on curvature improvement and do not gauge improvement in these girth loss or indentation features specifically. PD patients with calcification may benefit from CCH, however, critical analysis of included study designs and results compared to placebo do not lend for strong support of CCH in PD at this time. Conclusion: Based on the most recent research, the use of CCH in the acute phase of PD and patients with ventral penile plaques may be effective and safe. The limited available research on the efficacy of CCH on calcified plaque(s) and curvature greater than 90° is promising, however, more research is needed to ensure safety and success in this patient cohort. Finally, the current literature continues to show the use of CCH is not effective in PD patients with volume loss, indentation, or hourglass deformity. When expanding the use of CCH to patients not originally included in the IMPRESS trials, providers must prioritize minimizing chances of potential injury to urethral tissue. Finally, further investigation is required to determine whether CCH has utility for curvature greater than 90° or calcified plaques, although the limited available literature is promising.
... Currently, although surgery has been regarded as the golden standard treatment for PD in the chronic phase, non-surgical therapy still appears to be an important option to reduce penile deformity and improve erectile function (Wymer et al., 2019). Meanwhile, various conservative treatments have been researched and are available for PD patients (Randhawa and Shukla, 2019). As the only FDA-approved drug, intralesional CCH is well explored and is more effective than oral or topical medication for PD (Gabrielson et al., 2018;Zhang et al., 2021). ...
Full-text available
Background: Peyronie’s disease (PD) is a progressive fibrotic disorder of the penis that is adverse to men’s health. Currently, effective and reliable non-surgical options for PD are limited. Since the Food and Drug Administration (FDA) approved it in 2013, intralesional injection of collagenase Clostridium histolyticum (CCH) became the only licensed treatment for PD. This meta-analysis aims to evaluate the clinical efficacy and safety of CCH in treating PD, predominantly based on post-FDA studies. Methods: The primary outcome was clinical efficacy evaluated by the percentages of improvement in penile curvature (PC) and Peyronie’s disease symptom bother score (PD bother score). The secondary outcome was the safety assessed by treatment-related adverse events (TRAEs). Heterogeneity was assessed by Cochran’s Q and I 2 tests. Sensitivity and subgroup analyses were performed to explore the source of heterogeneity. Funnel plots and Egger’s test were used to evaluate the publication bias. Results: A total of 11 studies with 1,480 intentions to treat (ITT) population were included. The pooled effect of the improvement of PC was 35% (95% CI: 0.33–0.38), and the pooled improvement of the PD bother score was 41% (95% CI: 0.37–0.45). No heterogeneity was found at the pooled improvement of PC ( p = 0.845, I 2 = 0.00%). Meanwhile, some heterogeneity existed in the pooled improvement of the PD bother score ( p = 0.069, I 2 = 43.4%). The pooled effect of TRAEs was 93% (95% CI 0.88–0.97) with significant heterogeneity ( p < 0.000, I 2 = 92.3%). Conclusion: The intralesional injection of CCH could significantly improve the penile deformity of PD patients. Meanwhile, CCH appears to ameliorate the PD bother score to some extent and has acceptable clinical safety. Future studies are required to clarify the long-term outcomes of CCH injection in the treatment of PD.
... In the guideline published by the EAU in 2019, it is recommended that vitamin E should not be used in patients who want to significantly reduce the curvature. According to the International Consultation on Sexual Medicine 2016 guideline (ICSM), oral treatments have been reported to be minimally beneficial or not beneficial in reducing the clinical features of Peyronie's disease; therefore, their use is not recommended (30,31). ...
... Local injection therapy for lesions has been accepted recently, because of its rapid drug delivery, high local drug concentration, and ease of clinical operation (7,11). Currently, drugs for the local injection are mainly CCH, verapamil, and interferon-α2b, of which CCH is the most widely used (9,12,13). Previous clinical trials focused on the effectiveness of CCH (14)(15)(16), but most of them were reviews or case reports, lacking evidencebased medical evidence, and there are still some clinicians who are concerned about its safety and efficacy. ...
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Background Peyronie's disease (PD) is a chronic wound healing disorder, mainly involving tunica albuginea. Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial, which propelled us to conduct the first evidence-based research on this topic. Methods We searched the Web of Science, PubMed, Embase, and for related randomized controlled trials (RCTs). A systematic review and meta-analysis were performed to compare the penile curvature deformity (PCD), Peyronie's Disease Questionnaire peyronie's disease symptom bother (PDSB), penile pain score, total treatment-related adverse events (TAEs), and specific adverse events, including penile pain, penile edema, injection site pain, and contusion. Cochrane Collaboration's tool and Review Manager 5.3.0 version were applied, respectively, to evaluate the study quality and heterogeneity. Results Four articles (five RCTs) with 1,227 patients were finally included in the meta-analysis. The results revealed that CCH had excellent efficacy in relieving PCD (weighted mean difference [WMD]: −318.77, p < 0.001) and PDSB (WMD: −1.20, p < 0.001) compared to the placebo group, but there was no difference in the penile pain score (WMD: −0.64, P = 0.39) between the two groups. Furthermore, the incidence of TAEs in the CCH group was higher [odds ratio (OR): 12.86, p < 0.001]. Conclusions The current evidence suggests that CCH has a significant effect on treating PD. Considering that all these adverse events are acceptable and curable, CCH could slow the disease progression in the acute phase or act as a substitute for patients unable or unwilling to undergo surgery. However, the conclusion could not be certainly drawn until RCTs with a larger scale proved it.
... "Collagenase clostridium histolyticum", an enzyme, is produced by the bacterium Clostridium histolyticum (Brown 2017). This enzyme degrades the collagen plaques and thus is beneficial for the treatment of Dupuytren's contracture (Grazina et al. 2019) and Peyronie's disease (Randhawa and Shukla 2019). The topical formulation is used for the debridement of necrotic tissues due to burns or chronic ulcers. ...
Full-text available
Esophageal squamous cell carcinoma (ESCC) showed limited treatment outcome and poor prognosis. This study aimed to screen potential biomarkers and drugs in ESCC. Firstly, GSE26886, GSE111044 and GSE77861 were downloaded from the Gene Expression Omnibus (GEO) database. Next, the differentially expressed genes (DEGs) between cancer and noncancerous tissues were analyzed by the GEO2R. The Gene Ontology (GO) annotation, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, the protein-protein interaction (PPI) analysis and hub genes screened were conducted by some bioinformatic methods, respectively. Lastly, the hub genes and potential drugs were verified by the GEPIA2 and the QuartataWeb database. The results showed that 13 up-regulated genes and 81 down-regulated genes were identified. In GO terms, DEGs were mainly associated with cell proliferation, cell migration and cell differentiation. DEGs did not cluster into the KEGG pathway. After hub genes validated, nine genes (FLG, COL1A1, COL1A2, PSCA, SCEL, PPL, ACPP, CNFN, and A2ML1) expression trends showed no change. Moreover, higher COL1A1 or COL1A2 expression for ESCC patients showed poor prognosis. Finally, five drugs used for promoting blood coagulation were identified. Probably, these drugs could show anticancer effects by promoting blood coagulation or inhibiting vascular formation in cancers, which offers a novel idea for the treatment of ESCC.
... The authors believe use of the VED is the most critical maneuver in maintaining length and girth following Penuma ® removal. According to literature, VEDs are effective at promoting subcutaneous tissue engorgement (the opposite of healing contraction), cavernous tissue dilation, decreased venous outflow, and possibly increased arterial inflow [5]. Additionally, VED has been shown to have other medical benefits to penile cosmetics, specifically penile retraction, penile curvature, and penile lengthening prior to insertion of inflatable penile prosthesis and after radical prostatectomy during penile rehabilitation [6][7][8][9][10]. ...
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The Penuma® implant is a medical-grade silicone implant surgically inserted subcutaneously to provide cosmetic improvement of the penile aesthetic. The principal author was invited to provide an update on the usage of the Penuma® implant for penile aesthetics. He collected as yet unpublished data, which is undergoing synchronous submission to Urologic meetings and peer-reviewed publications by a variety of authors for this communication. The objective of this article is to provide updated information regarding the Penuma® aesthetic penile implant. A new scrotal method of implantation named “concealed” is emerging. Through physician comparison of various factors prior to and after the scrotal method intervention, early findings suggest this approach seems to have less visible scar, is quicker and is followed by less seroma formation. As the device is now surgically implanted by surgeons other than its inventor, new developments have appeared authenticating the original published paper in 2018. Patients were contacted via phone and were asked five questions regarding satisfaction with the responses recorded. This new multicenter study shows findings of high patient and partner satisfaction coupled with acceptable adverse outcomes similar to the single-surgeon study. A new penile rehabilitation program has been developed with the aim for the penis appearance to be restored to its pre-operative state if the Penuma® is removed. 12 patients who underwent penile implant removal were followed for 6 months while participating in the penile rehabilitation program. The discipline worked in patients who desired removal for dissatisfaction and is currently under evaluation in patients who require device removal for medical reasons, e.g., infection or suture-related issues. Through new developments, the acceptance of Penuma® in the prosthetic community seems to be further solidified.
... Several treatment options are offered to the patients while surgery is usually delayed until PD stabilizes, a process that in most patients reaches its definitive state after a period around 18 months from the initial presentation of PD [9]. Among the non-surgical options, the only FDA approved drug for injection directly into the deformity-causing penile plaque is a collagenase enzyme derived from clostridium histolyticum. ...
Background: Peyronie's disease is a condition that results in the development of penile plaques that can lead to penile curvature, pain, and erectile dysfunction, making sexual activity difficult. A number of non-surgical interventions exist to improve this condition, which include topical and injection agents as well as mechanical methods; however, their effectiveness remains uncertain. We performed this review to determine the effects of these non-surgical treatments. Objectives: To assess the effects of non-surgical therapies compared to placebo or no treatment in individuals with Peyronie's disease. Search methods: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings, up to 23 September 2022. We applied no restrictions on publication language or status. Selection criteria: We included trials in which men with Peyronie's disease were randomized to undergo non-surgical therapies versus placebo or no treatment for penile curvature and sexual function. Data collection and analysis: Two of four review authors, working in pairs, independently classified studies and abstracted data from the included studies. Primary outcomes were: patient-reported ability to have intercourse, quality of life, and treatment-related adverse effects. Secondary outcomes were: degree of penile curvature, discontinuation from treatment (for any reason), subjective patient-reported change in penile curvature, and improvement in penile pain. We performed statistical analyses using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach. Main results: Our search identified 1288 relevant references of which we included 18 records corresponding to 14 unique randomized controlled trials (RCTs) with 1810 men. These informed 10 distinct comparisons with relevant outcome data that were mostly extracted from single trials. In this abstract, we focus only on the most clinically relevant comparisons for the three primary outcomes and also include the outcome of degree penile curvature. Injectional collagenase (short-term): We found no short-term evidence on injectional collagenase for patients' self-reported ability to have intercourse and treatment-related adverse effects compared to placebo injection. Injectional collagenase may result in little to no difference in quality of life (scale 0 to 20 with lower scores indicating better quality of life; mean difference (MD) 1.8 lower, 95% confidence interval (CI) -3.58 to -0.02; 1 study, 134 participants; low CoE) and there may be little to no effect on the degree of penile curvature (MD 10.90 degrees less, 95% CI -16.24 to -5.56; 1 study, 136 participants; low CoE). Injectional collagenase (long-term): We also found no long-term evidence on injectional collagenase for patients' self-reported ability to have intercourse compared to placebo injection. It likely results in little to no effect on quality of life (MD 1.00 lower, 95% CI -1.60 to -0.40; 1 study, 612 participants; moderate CoE). Treatment-related adverse effects are likely increased (risk ratio (RR) 2.32, 95% CI 1.98 to 2.72; 1 study, 832 participants; moderate CoE). Injectional collagenase likely results in little to no change in the degree of penile curvature (MD 6.90 degrees less, 95% CI -9.64 to -4.14; 1 study, 612 participants; moderate CoE). Injectional verapamil (short-term): We are very uncertain how injectional verapamil may affect patients' self-reported ability to have intercourse compared to placebo injection short-term (RR 7.00, 95% CI 0.43 to 114.70; 1 study, 14 participants; very low CoE). We found no evidence for the outcome of quality of life. We are very uncertain how injectional verapamil may affect treatment-related adverse effects (RR not estimable; 1 study, 14 participants; very low CoE). Similarly, we are very uncertain how injectional verapamil may affect degree of penile curvature (MD -1.86, 95% CI -10.39 to 6.67; 1 study, 14 participants; very low CoE). We found no long-term data for any outcome. Extracorporeal shock wave treatment (ESWT) (short-term): We are very uncertain how ESWT affects patients' self-reported ability to have intercourse short-term (RR 1.60, 95% CI 0.71 to 3.60; 1 study, 26 participants; very low CoE). ESWT may result in little to no difference in quality of life (MD 3.10, 95% CI 1.57 to 4.64; 2 studies, 130 participants; low CoE). We are very uncertain if ESWT has an effect on treatment-related adverse effects (RR 2.73, 95% CI 0.74 to 10.14; 3 studies, 166 participants; very low CoE). ESWT may result in little to no difference in the degree of penile curvature compared to placebo (RR -2.84, 95% -7.35 to 1.67; 3 studies, 166 participants; low CoE). We found no long-term data for any outcome. Penile traction therapy (short-term): We found no evidence for whether penile traction compared to no treatment affects patients' self-reported ability to have intercourse. We are very uncertain how traction therapy may affect quality of life (MD 1.50 lower, 95% CI -3.42 to 0.42; 1 study, 90 participants; very low CoE). We are also very uncertain how traction therapy may affect treatment-related adverse effects (RR not estimable; 1 study, 90 participants; very low CoE) and how it affects the degree of curvature (MD 7.40 degrees less, 95% CI -11.18 to -3.62; 1 study, 89 participants; very low CoE). We found no long-term data for any outcome. Authors' conclusions: There is little evidence supporting the effectiveness of most non-surgical treatments for Peyronie's disease. Existing trials are mostly of poor methodological quality and/or fail to address patient-centered outcomes. Injectional collagenase appears to have some effectiveness; however, many individuals may not experience the improvement as clinically relevant, and this comes with the risk of increased adverse events. There is a critical need for better non-surgical treatment options for men with Peyronie's disease.
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This comprehensive scoping review aimed to identify all up-to-date original publications relating to substitute materials used for the surgical treatment of Peyronie's disease (PD), and characterize what material in which chronological trends were published in the current literature. Using the PCC framework (P: population, C: concept, and C: context), a search strategy was developed and used in four electronic databases, in addition to the Google scholar. All current published, in-press, and pre-print manuscripts with available English full-text were included. Eligible studies were required to be original research articles of any study design, reporting the usage of grafts on surgical treatment of PD. Included studies were reported in a narrative synthesis format. A total of 3379 articles were identified via an electronic search of databases and a total of 171 articles entered this scoping review. Most studies originated from Europe (n = 72) and North America (n = 66). Reports from the other continents increase in number in the 21st century. Highest number of the published papers was seen in 2001 to 2005 pentad. Autologous grafts (53.5%). Allografts (22.7%) and xenografts (15.7%) were the most frequently reported materials. Time flow of the used material and the alterations in trends for them is quite considerable. A global perspective of relevant publications on substitute materials in the surgical management of PD is presented in this review. The information in this summary may assist in establishing future research priorities in this area.
Urological conditions have become increasingly common and early diagnosis is key to achieving better outcomes. This article discusses the importance of having a comprehensive understanding of urological disorders, having the skills to interpret relevant information, and recognising the relationships among given elements to make an appropriate clinical diagnosis.
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Aim & Objective: To assess the efficacy of a new electromotive system for the transcutaneous delivery of verapamil or of hyaluronic acid to improve the symptoms of Peyronie' s disease (PD) in patients with a curvature deformity of < 30° at the beginning of therapy. Methods & Materials: Sixty-one PD patients were studied. Thirty were randomly assigned to receive verapamil 10 mg/session (Isoptin®, BGP Products, Rome-Italy), (Group 1, median age 56 years, range 49-62), and 31 were randomly assigned to receive hyaluronic acid 8 mg/session (Sinovial®, IBSA, Lodi-Italy) (Group 2, median age 58 years, range 51-56). There were ten sessions, 2 sessions/week for each drug. Each drug was transdermally administered using the hydroelectrophoresis technique and carried out using a Hydro4and apparatus (Swiss4Med SA, Morbio Inferiore, Switzerland). With respect to the efficacy of the drugs studied, the endpoints were: side effects, pain, erectile function, penile deviations and plaque area (cm2) before, and 3 and 6 months after drug administration. The differences were assessed using the Mann-Whitney Rank test (unmatched groups) or using the Wilcoxon Signed Rank test (matched groups). The differences between the groups in terms of side effects were assessed using the chi-square test. Results: No significant difference emerged among the baseline values of the two groups. Pain, erectile function, plaque area and penile deformity significantly improved in both groups after treatment, but a notably higher improvement occurred in the patients in whom hyaluronic acid was administered. Only a few negligible side effects occurred in the Group 1 patients treated with Verapamil, with no significant difference between the groups. Conclusion: Administration of both hyaluronic acid and verapamil using the Hydro4and apparatus is a safe and efficient method for PD therapy.
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Purpose: Autologous platelet rich plasma (PRP) is used increasingly in a variety of settings. PRP injections have been used for decades to improve angiogenesis and wound healing. They have also been offered commercially in urology with little to no data on safety or efficacy. PRP could theoretically improve multiple urologic conditions, such as erectile dysfunction (ED), Peyronie's disease (PD), and stress urinary incontinence (SUI). A concern with PRP, however, is early washout, a situation potentially avoided by conversion to platelet rich fibrin matrix (PRFM). Before clinical trials can be performed, safety analysis is desirable. We reviewed an initial series of patients receiving PRFM for urologic pathology to assess safety and feasibility. Materials and methods: Data were reviewed for patients treated with PRFM at our center from November 2012 to July 2017. Patients were observed immediately post-injection and at follow-up for complications and tolerability. Where applicable, International Index of Erectile Function (IIEF-5) scores were reviewed before and after injections for ED and/or PD. Pad use data was collected pre/post injection for SUI. Results: Seventeen patients were identified, with a mean receipt of 2.1 injections per patient. Post-procedural minor adverse events were seen in 3 men, consisting of mild pain at injection site and mild penile bruising. No patients experienced complications at follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations. Conclusions: PRFM appears to be a safe and feasible treatment modality in patients with urologic disease. Further placebo-controlled trials are warranted.
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Peyronie’s disease (PD) is an inflammatory disorder characterized by an abnormal collagen deposition in the tunica albuginea of the penis, leading to fibrous and non-compliant plaques that can impede normal erection. Although pharmacological treatments are available, only intralesional injection therapy and surgical reconstruction have demonstrated tangible clinical efficacy in the management of this condition. Intralesional injection of collagenase clostridium histolyticum (CCH) has come to the forefront of minimally invasive treatment of PD. In this review, the authors provide an update on the safety, efficacy, and indications for CCH. The efficacy of CCH will be assessed on the basis of improvement in the severity of penile fibrosis, curvature, and pain. Numerous well-designed clinical trials and post-approval studies involving more than 1,500 patients have consistently demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH significantly decreases penile curvature and plaque consistency, as well as improves quality of life. Post-approval studies continue to demonstrate the efficacy of CCH despite broader inclusion criteria for treatment, such as the case with acute phase disease and atypical plaque deformities (i.e., ventral plaques, hourglass narrowing). CCH continues to be the gold standard for non-surgical management of stable phase PD, in the absence of strong evidence supporting oral therapy agents and ongoing evaluation of extracorporeal shockwave therapy. However, recent studies are beginning to provide precedent for the use of CCH in the management of acute phase and atypical PD.
Introduction: Peyronie's disease (PD) has historically been managed by at least 1 treatment, including oral supplements or medications, intralesional injections, or surgery. Adjunctive mechanical therapies also have been described, including penile traction therapy (PTT) and vacuum erection devices (VEDs), although relatively limited data are available on their use with PD. Aim: To review and summarize the published literature on the role and efficacy of PTT and VED in men with PD. Methods: A PubMed search was performed of all publications on PTT and VED in men with PD from inception through September 2017. Main outcome measures: Changes in penile curvature, length, girth, erectile function, and adverse events with PTT or VED. Results: PTT and VED exhibit mechanisms to improve aspects of PD, although clinical outcomes data are limited. Based on current data, PTT likely has a potential role as a primary lengthening therapy (modest improvements), in curvature correction (acute phase; unclear role in chronic phase), before penile prosthesis insertion, and after surgical correction of PD. The role of PTT as a combination therapy during collagenase Clostridium histolyticum injections is unclear. Fewer and lower level-of-evidence studies are available on VEDs and suggest potential roles in curvature correction, before penile prosthesis placement, or after PD surgery. Guideline statements from the American Urological Association and International Consultation on Sexual Medicine also support the potential role of PTT and VED in managing PD. Conclusions: PTT and VED represent viable therapeutic options for managing PD, with more data currently available on PTT. Because all PTT studies used a similar style of traction device, it is unclear whether results reflect outcomes of these particular devices or traction more broadly. Further studies are required to better delineate the benefits of PTT and VED, particularly in relation to other established treatments. Avant RA, Ziegelman M, Nehra A, et al. Penile Traction Therapy and Vacuum Erection Devices in Peyronie's Disease. Sex Med Rev 2018;X:XXX-XXX.
Background: Penile traction therapy with the use of a traction device (TD) or vacuum erectile device (VED) has been studied as local modalities for Peyronie's disease (PD). Aim: To identify changes of penile curvature, erectile function, and possible cellular and molecular mechanisms between the TD and VED in a rat model of PD. Methods: Peyronie's plaque was induced in 30 adult male rats. Then, rats were randomly divided into control (PD without treatment), VED, and TD groups. In the VED group, vacuum pressure was applied to the cylinder to induce penile engorgement inside the cylinder for 1 minute. The penis was allowed to deflate completely for another 1 minute. This was repeated for five cycles (inflate and deflate). In the TD group, the rat penis was straightened by a suspended tension gauge at the same tension by clamping the prepuce. This was performed three times per day at 20 minutes per session, with 5-minute intervals between sessions. The entire treatment duration was 4 weeks. Outcomes: Penile curvature, intracavernosal pressure, and mean arterial pressure were measured. Immunohistochemistry for α-smooth muscle actin, transforming growth factor-β1 and mothers against decapentaplegic homolog 2/3 were performed. Results: The TD and VED groups had less penile curvature compared with the control group (15.3 ± 5.3° for TD, 28.4 ± 6.8° for VED, 38.6 ± 10.5° for control; P < .001 for TD vs control, P < .05 for VED vs control). The TD group also had less penile curvature compared with the VED group (P < .05). The VED group had a higher ratio of intracavernosal pressure to mean arterial pressure compared with the two other groups (0.56 ± 0.10 for VED, 0.38 ± 0.06 for TD, 0.32 ± 0.07 for control; P < .001). The immunohistochemistry results showed the VED group had more preserved α-smooth muscle actin with less transforming growth factor-β1 and mothers against decapentaplegic homolog 2/3 than the TD and control groups in the corpus cavernosa. Clinical translation: Various benefits can be observed with the TD and VED for the treatment of PD. Strengths and limitations: This study explored the mechanism and benefits of TD and VED therapies for the treatment of PD. The rat model might not represent the human condition. Conclusion: Penile traction therapy with the TD or VED is beneficial to decrease penile curvature in animal models of PD. The underlying mechanism could be related to antiapoptosis, antifibrosis, and smooth muscle preservation. Lin H, Liu C, Wang R. Effect of Penile Traction and Vacuum Erectile Device for Peyronie's Disease in an Animal Model. J Sex Med 2017;XX:XXX-XXX.
Introduction: Peyronie's disease (PD) is a connective tissue disorder resulting in the abnormal accumulation of type I to III collagen, fibrin, and disorganized elastic fibers in the tunica albuginea of the penis. Many medical and non-pharmacologic modalities have been used in the treatment of PD; however, these approaches have proved largely ineffective, with surgery being the only definitive treatment. Intralesional injection of collagenase Clostridium histolyticum (CCH) has recently become the gold standard for minimally invasive treatment of PD, and studies have suggested the role of CCH could expand to the treatment of other urologic conditions such as urethral stricture disease. Aim: To provide an update on available data on the use of CCH in the treatment of PD and other urologic conditions. Methods: Comprehensive review of recent clinical trials and in vivo studies that examined the safety and efficacy of CCH in urologic disease. Main outcome measures: Assessing the efficacy of CCH in the management of PD as determined by improvement in the severity of penile fibrosis, curvature deformity, and pain. Results: Several well-designed clinical trials have demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH has demonstrated significant decreases in penile curvature and plaque consistency and improvements in patient satisfaction. Treatment durability and long-term adverse effects are still being assessed; however, outcomes of PD management with CCH continue to replicate the results obtained during the IMPRESS clinical trials. Preliminary studies support the premise that CCH can modify disease progression in patients with acute-phase PD. Furthermore, one in vivo study showed that CCH also could be applied to urethral stricture disease without serious adverse complications. Conclusion: CCH continues to be the mainstay for non-surgical management of stable-phase PD. However, its role in the treatment of acute-phase PD, PD with ventral plaques, and urethral stricture disease could expand in the coming years. Gabrielson AT, Spitz JT, Hellstrom WJG. Collagenase Clostridium Histolyticum in the Treatment of Urologic Disease: Current and Future Impact. Sex Med Rev 2018;6:143-156.