Peyronie Disease Treatment & Management

Updated: Jan 28, 2023
  • Author: Eli Lizza, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Medical Therapy

The optimal medical therapy for Peyronie disease (PD) has not yet been identified. If the pain and/or curvature are minimal and do not preclude normal sexual function, refraining from medical treatment and observing the patient are reasonable. Observation can be continued as long as the condition remains stable.

To quantify the level of spontaneous improvement that can be expected, Mulhall et al conducted a prospective analysis of 246 men with PD. [26] These men were originally seen within 6 months of symptom onset and were observed without treatment for at least 12 months following symptom onset. The mean baseline penile curvature in these patients was 42°. PD improved (mean change of 15°) in 12% of the patients, remained unchanged in 40%, and worsened (mean change of 22°) in 48%. All patients who initially described penile pain reported improvement, while 89% noted complete pain resolution, again without any treatment. Mean flaccid penile length decreased during observation from 12.2 cm to 11.4 cm, which was not statistically significant.

When a specific therapy is evaluated, it is important to consider the placebo effect. This is especially applicable to PD since some of the symptoms of PD can spontaneously improve without therapy in a significant number of men.

In 2013, the US Food and Drug Administration (FDA) approved the first drug treatment for PD, collagenase clostridium histolyticum (Xiaflex). It is a proteinase that hydrolyzes collagen. CCH is available only in the United States and Canada; Endo Pharmacauticals withdrew Xiaflex from Australia, Asia, Europe, and the Middle East in 2019. The manufacturer stated its decision to withdraw the product was not based on safety or efficacy concerns. [27]  For more information on efficacy, see Injection Therapy, below.

A comprehensive review of the literature on the nonsurgical treatment of PD by Muller and Mulhall found that most published studies were underpowered. These authors also noted a remarkable heterogeneity in the methodological approach and patient assessment among the studies reviewed. There were problems with randomization, placebo control, and end-point evaluation. They also noted difficulty in the ability to characterize the type and degree of deformity. [28]

The duration of PD also presented a problem. Typically, PD is differentiated into an acute (early) phase and a chronic (delayed) phase, but the division between the two is not absolute. Only a few (15%) of the 26 studies reviewed analyzed the safety of the intervention or were placebo-controlled (19%). The results of intervention in these studies were not always discussed in terms of their clinical significance rather than just their statistical significance. The authors used the example that a reduction of curvature from 60º to 50º by an intervention might be statistically significant, based on the number of subjects, but would not significantly affect the patients' function.

In their assessment of the literature, these authors identified the following important points:

  1. The penile deformity is best evaluated by re-dosing intracavernous injection to achieve a full erection.
  2. All methods of plaque measurement are inaccurate except for penile MRI, which was not used in any study reviewed.
  3. Pain usually abates within 12-18 months regardless of treatment, so that is not useful as a therapeutic endpoint.
  4. Shortening of the duration of pain, on the other hand, may be an acceptable endpoint.
  5. The relationship between PD and erectile dysfunction (ED) is difficult to assess since there is no specific validated scale to assess the level of ED in patients with PD.
  6. Patient satisfaction, which may be the most meaningful outcome assessment, was rarely addressed (4% of studies).

These results must be considered when evaluating interventions that may expose the patient to untoward side effects or complications with little improvement in results over what can be expected from observation alone.

Oral preparations

When therapy is used, initiate medical treatment first. Several oral preparations have been used with varying degrees of effectiveness. While strong evidence of effectiveness is lacking, in general, better results have been reported for combination therapies compared with monotherapies. [29]

The antioxidant vitamin E has been used since 1948 because of the low incidence of adverse effects and its low cost. The effectiveness of vitamin E that was initially reported has not been confirmed by subsequent investigators. At the US National Institutes of Health conference on PD in 1993, Devine and Snow reported on 105 patients treated with oral vitamin E. These patients reported a 99% reduction in pain and a 13% reduction in penile curvature, even though 70% of the patients were found to have no objective change in their symptoms. This speaks to the need for properly validated studies with placebo-controlled groups and well-defined, measurable endpoints of treatment.

Another oral agent that has had varied success in treating this condition is potassium aminobenzoate ([PABA] Potaba). This compound is considered to be a member of the vitamin B complex. The antifibrotic action of PABA may be due to its production of increased oxygen uptake at the tissue level, which enhances oxygen-dependent monoamine oxidase activity, which, in turn, prevents or causes regression of tissue fibrosis.

Zarafonetis and Horrax first reported on the use of PABA to treat PD. All 21 men studied reported a reduction in pain, 82% noted an improvement in penile curvature, and 76% experienced a decrease in plaque size. [30]

In a retrospective study, Carson found a decrease in penile plaque size in 18 of 32 patients and a resolution of penile angulation in 18 of 31 patients treated with 12 g of PABA daily for at least 3 months. [31] Of 31 patients, 8 also reported complete resolution of angulation. Carson recommended that a prospective, double-blinded, multicenter, well-controlled study using objective criteria be performed to confirm his findings.

PABA has been the medical treatment used most frequently by the authors as first-line therapy. Unfortunately, therapy requires a large amount of PABA to be taken each day for a usual 6-month course. Most patients find the adverse gastrointestinal effects to be intolerable. In the continued absence of a well-controlled prospective study, it is difficult to recommend this therapy.

Colletta et al reported that the nonsteroidal antiestrogen tamoxifen facilitates the release of transforming growth factor–beta from human fibroblasts in vitro, which can result in inhibition of the inflammatory response and a decrease in fibroblast production. [32] Ralph et al reported on 36 men receiving 20 mg of tamoxifen twice daily for 3 months. [33] Sixteen of 20 patients reported improvement in penile pain, 11 of 31 had improved penile curvature, and 12 of 35 were noted to have a reduction in the size of their penile plaque.

However, in a more recent prospective, randomized, placebo-controlled study, Teloken et al found no significant improvement in pain, penile curvature, or plaque size in 25 patients with PD who were treated with tamoxifen. [34] These patients received either 20 mg of tamoxifen twice daily for 3 months or a placebo for the same time period. Evaluations were performed before treatment and 4 months after treatment. In view of this last report, tamoxifen does not appear to be of value in treating PD.

The anti-inflammatory agent colchicine has been shown by Fell et al and by Harris and Krane to decrease collagen formation and to stimulate collagenase activity by interfering with the transcellular movement of collagen and by decreasing collagen-processing enzyme activity. [35, 36] In a noncontrolled study, Akkus et al reported on 24 men who used colchicine for 3-5 months. [37] A slight decrease in curvature was noted by 11% of patients, a marked decrease was reported by 26%, and a decrease in plaque size occurred in 50%. Levine noted that most patients have poor tolerance of colchicine and frequently report gastrointestinal disturbances. [38]

Prieto Castro et al reported on the results of a prospective, single-blinded, randomized study comparing vitamin E at 400 mg/d and colchicine at 1 mg every 12 hours together (n = 23) with ibuprofen at 400 mg/d as a control (n = 22) for 6 months. [39] The men treated in this study were all in the early stages of the disease and had their symptoms for 6 months or less. They also had to be free from associated ED, have a curvature of not more than 30°, and have no calcification in their plaques. No significant difference in pain response was noted between the 2 groups. Plaque size increased in the group receiving ibuprofen, while it decreased in the vitamin E/colchicine group; the difference was significant. The change in penile curvature was also significant. Adverse effects included temporary diarrhea in 4 of 23 men taking colchicine.

The limitations of this study include the small sample size and the single-blinded study design. In spite of these limitations, this study indicates that the combination of vitamin E and colchicine may be an effective oral therapy for early mild cases of PD. Larger, double-blinded studies are necessary to confirm these findings.

Safarinejad reported the results of a randomized double-blinded, placebo-controlled study comparing the effects of colchicine to placebo in 78 men. [40] Although pain resolved in 60% of patients treated with 0.5-2.5 mg/d of colchicine orally for 4 months, it also resolved in 63.6% of those treated with placebo. Similarly, no differences in the reduction of penile deformity or decrease in plaque size was noted between the 2 groups. Safarinejad found no substantial differences between colchicine therapy and placebo. Furthermore, significant drug-related adverse effects were reported in the colchicine group, and these effects required cessation of therapy in 2 patients.

Injection therapy

Collagenase clostridium histolyticum (CCH) is an injectable proteinase that hydrolyzes collagen in its native triple-helical conformation, resulting in lysis of collagen deposits. It is believed to work for PD by breaking down the buildup of collagen that causes the curvature deformity. 

CCH is indicated in men with a palpable plaque and penile curvature deformity of at least 30º at the start of therapy. It is available for treatment of PD only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program called the XIAFLEX REMS Program. Currently Xiaflex remains he only FDA-approved injection therapy for PD.

FDA approval was established by two phase 3 randomized, double-blind, placebo controlled studies (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies [IMPRESS I and II]). These studies included 832 men with PD with penile curvature deformity of at least 30º. Participants were given up to 4 treatment cycles of CCH or placebo and were then followed 52 weeks. Treatment with CCH significantly reduced penile curvature deformity and related bothersome effects compared with placebo (P = 0.0037). [41]

A study of 69 men who underwent one to four series of CCH injections for PD at a single institution found that 88% reported subjective improvements after four series of injections. Objective measures demonstrated a mean 23º curvature improvement (38%, P < 0.0001). [42]  However, in another study of 45 men treated with one to four CCH injections for PD, the mean primary curvature was 53.6° and post-treatment mean primary curvature was 48.2° (P = 0.10); most of the men (37) expressed dissatisfaction with the treatment and did not see a change in curvature. [43]

In a prospective study that included 115 patients with PD who completed two or more cycles of CCH therapy, Wymer et al reported that CCH therapy was significantly more likely to be successful (curvature improvement ≥20°) in patients who had non-calcified plaques (odds ratio 2.50; P=0.03) and in patients with greater baseline curvature (≥60°). [44]  In a study of 135 patients treated with CCH, Cocci et al reported that patients with longer duration of PD, greater baseline penile curvature, and basal plaque location had a greater chance of treatment success. [45]

Abdel Raheem et al reviewed the literature on the use of CCH and confirmed the safety and efficacy of this treatment method. [46]  They present a shortened, modified protocol in which up to 3 single doses of 0.9 mg/vial CCH are injected 4 weeks apart, using a single skin puncture and  injecting the plaque along 3 lines around the plaque for each of these injections. They also advocate the use of a vacuum erection device after 24-72 hours and self-stretching of the penis at home. These authors found their results to be comparable to those of the IMPRESS trials in their first 53 patients. No cases of corporal rupture or unanticipated adverse effects were reported with the modified protocol. Benefits of this approach include shorter duration of treatment (12 vs 24 weeks) and significantly lower medication cost. 

In a review of treatment for PD, Capoccia and Levine recomended that the optimal non-surgical treatment involves a combination of oral, intralesional, and external traction therapies. However, they concede that the optimal combination of medications remains elusive. [47]

Zhang et al conducted a meta-analysis of 11 published prospective studies on the use of CCH for PD, starting with the original IMPRESS studies and spanning 2010 to 2021. [48] The meta-analysis confirmed that CCH results in improvment in penile curvature and PD bother scores, and also may help ameliorate psychological and penile pain symptoms. Both the original and the shortened treatment protocol appeared to be effective. Serious treatment-related adverse events were rare.

An alternative approach was taken by Culha et al, who treated 38 patients with both PD and ED. [49] These patients received a combination of oral colchicine and vitamin E along with intracavernous injection therapy using prostaglandin E1 (PGE1). The authors used a questionnaire to assess patient quality of life before treatment and 10 months after treatment and found improvement in all parameters. Symptoms were reported to diminish in 24 men. The authors note that none of these men started the study with severe curvature of the penis or intolerable pain while erect. Nevertheless, this combination therapy may be beneficial in selected men with PD and ED whose symptoms are not severe.

Intralesional injection of various substances has been used for decades in an attempt to dissolve the plaques of PD. Winter and Khanna reported decreased plaque size and penile pain after injection of dexamethasone. [50] Williams and Green found marked improvement in symptoms after injection of triamcinolone hexacetonide every 6 weeks for 36 weeks. [51] These investigators concluded that men with small, firm, discrete nodules were most likely to respond. Both studies noted the presence of marked local adverse effects from the intralesional injections, which could complicate subsequent surgery.

More recently, Cipollone et al addressed the use of intralesional injection with betamethasone in a prospective, randomized, placebo-controlled study of 30 men. [52] At 12-month follow-up, no significant differences were noted between the placebo group and the steroid group with respect to the disappearance of pain, a decrease of plaque volume, or a decrease of penile curvature. Interestingly, at 12 months, figures for all 3 parameters had decreased, noting a disappearance of pain with erection in 66.6% of the treated group versus 53.3% of the control group, a decrease in plaque volume in 40% of the treated group versus 40% of the control patients, and a diminishment of curvature in 20% of the treated patients versus 26.6% of the control patients.

The authors concluded that the effect was likely due to a mechanical effect of the injected volume rather than the specific agent used. However, this also might represent the natural progression of the disease and may not be related to this treatment. This study also points to the need to use prospective, randomized, placebo-controlled studies before drawing conclusions regarding the efficacy of any therapeutic intervention.

In another study, Lamprakopoulos et al treated 112 men with intralesional betamethasone and hyaluronidase injections. [53] Each received 12 injections. The authors reported that 31% of patients were cured and that another 55% were improved. However, they stressed that the treatment appeared most efficacious in men with smaller lesions (£20 mm) that were of recent onset (< 12 mo). This study was neither randomized nor placebo-controlled. In view of the previous study, these results appear less dramatic.

The calcium channel blocker verapamil has gained attention for the treatment of PD since Lee and Ping found that it induced increased collagenase activity. [54] Levine et al first published results of the use of intralesional verapamil for PD in an uncontrolled study in 1994, reporting reduced pain in 93% of men treated with 10 mg of verapamil injected intralesionally. They also noted 100% subjective improvement in hourglass deformity, 42% objective improvement in curvature, and 58% improvement in ED. [55]

Subsequently, a nonrandomized constant dose study of intralesional verapamil injection by Lasser et al reported significant decrease in plaque size in 7 (55%) of the 11 study patients, softening of the plaque in 6 (55%) patients, decreased curvature in 4 (50%) of 8 men, and resolution of pain in 4 (100%) of 4 men. [56] Nine of the study subjects also received concurrent therapy with either testosterone or PABA. A single-blinded study by Rehman et al that compared intralesional verapamil injection with saline injection as a control noted benefit with verapamil in men with noncalcified plaques and penile angulation of less than 30°. [57] Collectively, these studies reported minimal complications and no arrhythmias or hypotensive episodes.

Cavallini et al reported the results of administering intraplaque injections of verapamil at different dilutions. [58] A total of 77 men were divided into 3 groups and received 10 mg of verapamil diluted in 4 mL, 10 mL, or 20 mL. At 8 months, the plaque area, penile curvature, erectile function, end-diastolic velocities of the left and right cavernosal arteries, and pain were most improved in the group who received verapamil diluted in 20 mL. This result again points to the volume of the injection as being more important than the verapamil.

Another calcium channel blocker, nicardipine, demonstrated efficacy for treatment of PD in the transition period between the acute and chronic phase. A prospective, randomized, single-blind trial by Soh et al used a dorsal penile block with 1% plain lidocaine followed by intralesional injection of either 10 mg of nicardipine diluted in 10 mL of distilled water (n = 37) or 10 mL of normal saline alone as a control  (n = 37). A 5/8-inch, 27-gauge needle was used. Each group received 6 biweekly injections. [59]

Compared with the control group, the nicardipine group experienced significantly better pain control (P = 0.019), significant improvement in International Index of Erectile Function (IIEF)-5 scores at 48 weeks after initiation of treatment (P < 0.01), and decrease in plaque size at 48 weeks  (P = 0.0004). Penile curvature significantly improved in both groups (P < 0.01) without significant difference between the groups (P = 0.14). No severe cardiovascular adverse effects occurred. All the study subjects had acute PD and had been treated with oral vitamin E for 6 months before entering the study. Further studies are necessary to determine if nicardipine is more efficacious than verapamil in this setting.

Moskovic et al reported data from 131 men with PD for less than 1 year who received bimonthly injections of intralesional verapamil. [60] Penile curvature was assessed at baseline and after 3 months of therapy. Patient age younger than 40 years and penile curvature of more than 30º were each predictive of a favorable outcome, defined as a decrease of more than 10º from baseline.

Although these studies appear to demonstrate a benefit from intralesional verapamil, drawing a definitive conclusion on the efficacy of this treatment remains difficult without a well-constructed, double-blinded, placebo-controlled study. In lieu of such data, a larger cohort from a multicenter collaborative study would be more beneficial.

However, offering intralesional verapamil to younger men appears to be appropriate, especially if their degree of curvature is 30-60º. Although the optimal concentration has not yet been confirmed, most investigators use 10 mg of verapamil in 10-20 mL of sterile water. The most common frequency of injection is every 2 weeks and the duration of treatment ranges from 10 weeks to 6 months.

Intralesional hyaluronic acid (HA) injections have also been studied for the treatment of PD. A double-blind randomized study by Favilla and colleagues that compared HA with verapamil injection in 132 men reported a statistically significant improvement in plaque size (–1.36 mm and –1.8 mm) and IIEF score (1.46 and 1.78) in the verapamil and HA group, respectively. In the HA group, penile curvature decreased 4.6°(standard deviation ± 5.63) whereas no decrease was seen in the verapamil group. [61]

An open-label prospective study by Cocci et al that compared intralesional HA with verapamil for the treatment of acute-phase PD showed similar modest improvement in penile curvature and penile plaque in both groups, with no significant difference between the groups. [62] In the study, which comprised men with a palpable plaque or nodule and progressive penile curvature greater than 15º and/or pain within the last 12 months, 125 men received intralesional HA and 119 received intralesional verapamil. Both groups received injections weekly for 8 weeks and were assessed 3 months after therapy. Limitations of this study include the absence of a placebo control group, lack of randomization, short duration of follow-up, and small sample size.

Electromotive administration

Another approach to the delivery of medication to a Peyronie plaque is electromotive drug administration (EMDA), also known as iontophoresis. In this approach, the electrokinetic transport of charged molecules is used to enhance the transdermal application of a drug. Riedl et al reported benefit from EMDA use in an uncontrolled, prospective study that included 100 patients. [63] A mixture of dexamethasone, lidocaine, and verapamil in a self-adhesive receptacle was placed over the plaque and an electrical current of 5 mA applied. These authors reported resolution of pain in 96% of patients, diminution of plaque in 53%, improvement of penile deviation in 37%, and improvement of ED in 44%.

Montorsi et al treated 40 men with PD by EMDA with orgotein, dexamethasone, and lidocaine in a double-blind, placebo-controlled, partial crossover study (study 1).They also reported an uncontrolled study in 25 men who received EMDA with verapamil and dexamethasone (study 2).  In both studies, sessions used 3 mA of current for 20 minutes 3 times a week, with assessment at 1 and 3 months after the initiation of therapy. Penile pain resolved completely in 100% of men, penile plaque improved significantly or resolved completely in 79% of study 1 patients and in 90% of study 2 patients, and penile deformity improved in 62% of study 1 patients and 88% of study 2 patients; penile rigidity improved by more than 80% in both groups. [64]

The benefit of this therapy appears to be more pronounced in patients with a short history of debilitation (ie, in men in the initial stages of PD). The main advantage of this treatment is that administration is painless. Neither group reported adverse effects.

Martin et al investigated the use of transdermal verapamil without EMDA to see whether the drug would be absorbed through the skin. [65] A commercially available preparation of verapamil gel (0.5 mL, 40 mg/mL) was applied to the penises of men scheduled for penile implantation on the night before and the morning of their surgery. The level of verapamil was measured in the urine and the tunica. No adverse effects were noted. Although small levels of verapamil were identified in the urine (signifying a low level of systemic absorption), none was identified in the tunical tissue. These authors concluded that no rationale supports the topical use of verapamil for PD. This finding may not apply to other topical verapamil preparations; however, the authors make a strong case against the use of topically applied verapamil without EMDA.

Levine et al reported that EMDA is a safe technique that is capable of transporting verapamil into the tunica albuginea. [66] This noncontrolled, nonrandomized, single-blinded study used either verapamil at 10 mg alone or verapamil with epinephrine for 20 minutes in men with PD who then immediately underwent plaque excision. The levels of verapamil in the excised tunica were compared with levels in the tunica from men who either had no treatment or who had intralesional injection of verapamil. These authors found detectable levels of verapamil in 10 (71.5%) of 14 men treated with topical verapamil with EMDA. Epinephrine, which was used to decrease vascular dispersion, did not increase tunical concentrations. This study did not address the question of whether the verapamil helps the PD at these levels.

Di Stasi reported benefit of EMDA in a prospective, nonblinded study of 49 men. [67] The study involved treatments with verapamil at 5 mg and dexamethasone at 8 mg with EMDA 4 times a week for 6 consecutive weeks. Pain resolved in 88%, curvature disappeared in 10% and improved greater than 50% in 35%, plaque disappeared in 8% and diminished by more than 50% in another 14%, ED resolved completely in 42% and improved in another 17%, and vaginal penetration was possible after treatment in 68% and improved in another 5%. The authors found that results were better in men with smaller, noncalcified plaques. The small sample and the nonblinded study design detract from the significance of this study, although it does meet the criteria for evidence-based research.

Subsequently, Di Stasi et al reported on the results of a prospective, randomized, controlled, double-blind study of 73 men treated with either verapamil at 5 mg and dexamethasone at 8 mg diluted to 5 mL (study group) or 5 mL of lidocaine 2% (control group) with EMDA. [68] Each participant received 4 sessions per week, each lasting 20 minutes, for 6 consecutive weeks. Compared with the control group, patients in the treatment group experienced a significant decrease in plaque volume, a significant improvement in penile deviation, and significant relief of erectile pain.

Indeed, while no patient in the control group exhibited complete resolution of either the plaque or the penile deviation, the plaque resolved completely in 5 (14%) of the treated patients, and penile deviation resolved completely in 5 (14%). Erectile activity was regained in 11% of the control group compared with 51% in the treatment group. Although transient erythema was reported at the sites of the electrodes in all patients, no other adverse effects were reported. [68]

An editorial by Wessells observes that this study does not comment on the men who dropped out, nor does it demonstrate that the mechanism of PD is regulated by either of these drugs. [69] In spite of these drawbacks, the power of the study design is significant as evidence-based research, and the results are compelling.

Extracorporeal shockwave therapy

An alternative approach has been to try to disrupt the plaque by means of mechanical force using extracorporeal shockwave therapy (ESWT). A prospective trial by Mirone et al used a Minilith SL1 lithotriptor (Storz Medical AG, Kreuzlingen, Switzerland), which is commonly used to treat salivary stones, for 3 ESWT sessions of 20 minutes each. In 21 patients, ESWT was the only treatment; in a second group of 36 patients, ESWT was followed by a cycle of 12 perilesional injections of 10 mg of verapamil every 2 weeks. They compared the results in these groups with their 73 previously treated men who had received only the verapamil injections. They noted reduction of plaque in 11 of the 21 men in the first group and in 7 of the 36 men in the second group. The treatment was well tolerated. [70]

A long-term study of ESWT for PD by Srirangam et al found that on post-treatment follow-up of 42-48 months, 18 (47%) of the 38 patients had a statistically significant reduction in angulation, with a mean reduction of 33.2º. 10 (26%). Of the remaining patients, 10 had undergone corrective surgery for failed ESWT. [71]

Husain et al treated 37 men with a minimum of 3 treatments at 3-week intervals. [72] They noted a 47% improvement in angulation, and 60% reported relief of penile pain. Both studies reported minimal penile bruising as the only adverse effect. However, many investigators are concerned that ESWT will induce more inflammation to the tunica than it will eradicate.

Hauck et al reported on a prospective study of 114 patients who were treated with ESWT during one session consisting of 4000 shockwaves. [73] An Australian study concluded that ESWT was safe, somewhat effective, and had a high patient satisfaction rate. [74]   The study was initiated as case-controlled, but because the response to medical treatment was so poor and because so many patients desired ESWT, it was converted to a prospective study. Patients were accepted with and without calcification of the plaques and regardless of whether they were in the active or stable stage of their disease.

No significant change was noted in plaque size, penile curvature, or sexual function after ESWT. Penile pain was relieved in 76% of treated patients. The authors found that, in the subgroup of patients with penile curvature of 31-60°, ESWT seemed to have a significant effect on decreasing penile curvature. They also noted that penile pain appeared to resolve more rapidly after ESWT than during the natural course of the disease. In spite of these findings, the authors concluded that, based on their findings, "ESWT should not be recommended as a standard procedure for Peyronie's disease."

Hauck et al completed an exploratory meta-analysis of treatment outcomes from 17 study groups compared with natural history outcomes and with control groups from 2 of the studies. [75] The authors found that ESWT seemed to help resolve penile pain faster and seemed to help ED but had a questionable effect on penile plaque and curvature. They concluded that based on the available literature and because of the lack of controlled studies, ESWT is not an effective evidence-based therapy at the time of their review.

Interferon alfa-2b

Interferon alfa-2b (IFN a-2b) has been found by Duncan et al to affect the production of collagen in human fibroblasts derived from Peyronie plaques by inhibiting fibroblast proliferation and stimulating collagenase activity. [76] This naturally occurring, low molecular weight protein is part of the immune system, interfering with viruses and causing antiproliferative and antitumorigenic effects. Wegner et al were the first to report the use of intralesional IFN a-2b to treat PD in 1995. [77] These authors demonstrated decreased penile pain, decreased penile curvature, and diminished plaque size. However, these same authors reported 2 years later on the results of 90 treatments in 30 men with early PD. They found the treatment to be unsuccessful. The disease continued to progress in 25% of their patients, and the adverse effects were intolerable. Myalgia and fever were noted with 74 of 90 treatments.

Other authors have noted more encouraging results. Judge and Wisniewski reported improvements in penile pain, curvature, plaque hardness, and plaque size compared with controls in a study of 13 men with PD. [78] Ahuja et al reported resolution of penile pain in 90% of men with PD, significant improvement in curvature in 65%, and objective decrease in plaque size in 85%. [79] Astorga et al reported on 34 patients treated with intralesional IFN a-2b (10 million IU) twice weekly for 14 weeks. [80] These authors reported that ED disappeared in 79.2% of patients, palpable lesions resolved in 62%, curvature resolved in 47%, and a complete clinical response was noted in 16 (47%) of 34 men, including 5 men in whom other treatments had failed.

Brake et al noted poor results after a 3-week course of injections of 2 million IU of IFN a-2b three times per week in 23 patients. [81] Although 13 of 19 patients with pretreatment pain were rendered pain free, no significant change was noted in penile deviation or plaque size in any of the patients, and only 7 (30%) described an improvement in sexual function. Overall, only 26% of patients were satisfied with their outcome.

All of these studies describe significant rates of adverse effects with IFN a-2b therapy, most commonly flu like symptoms and fever, but also hematomas, penile edema, penile cysts requiring surgical excision, and the development of venous leak.

Hellstrom et al reported on a single-blind, multicenter, placebo-controlled, prospective, parallel study that examined the safety and efficacy of intralesional IFN a-2b as a minimally invasive treatment for PD. [82] Fifty five men received IFN a-2b at a dose of 5 million IU dissolved in 10 mL normal saline biweekly for 12 weeks using the multipuncture technique. Sixty two men received 10 mL normal saline only.

The authors reported significantly greater improvement in penile curvature, penile plaque size and density, and resolution of penile pain in the treated group compared with the placebo group. The flulike side effects did not contribute to dropout. This was a well-performed study, and its findings are statistically significant. However, they must be tempered by the fact that the mean penile curvature changed in the treatment group from 50° to 36°. This reflects only a partial response to the treatment. Further, a significant improvement was noted in the placebo group, who received only normal saline. This implies a therapeutic hydrostatic effect from the injection procedure. It would appear from the above that, although these findings may be statistically significant, they may not be clinically significant as therapeutic options.

Inal et al presented a randomized prospective study or 30 patients that compared treatment with oral vitamin E alone, intralesional IFN a-2b alone, and a combination of both simultaneously. [83] The authors found no statistically significant changes in plaque size or penile curvature within each group or among the 3 groups. They also found no difference in the quality of intercourse or in the presence of penile pain among the groups. This was a relatively small study, with only 10 patients randomized to each group. The authors concluded that "intralesional IFN a-2b therapy either alone or in combination with vitamin E is invasive and expensive and has limited effects on early stage PD with significant side effects."

In a prospective study of intralesional intralesional interferon alfa 2b (IFN-α2b) treatment for PD, Sokhal et al reported significant improvement in plaque volume and penile curvature, as well as patient reports of improvement in pain on erection and sexual activities. Complications were minimal. The clinical outcome of IFN-α2b treatment was similar to that reported in the literature with verapamil; however, the cost of IFN-α2b treatment was much higher than that of verapamil. [84]

This therapy continues to require further prospective, placebo-controlled, double-blinded, multi-institutional studies with long-term follow-up before it can be recommended for use in treating PD.

Platelet-rich plasma injections

The premise of platelet-rich plasma (PRP) therapy for PD is that the platelets injected into the plaque tissue will secrete the various chemokines and cytokines that mediate inflammation, along with various growth factors that stimulate an immune response and promote wound healing. In practice, PRP requires intralesional injection of concentrated platelet solutions reaching up to 7 times physiologic levels. A systematic review by Alkandari et al of PRP injections for ED and PD concluded that this treatment may be promising, but evidence is currently too scarced to support recommending it. Instead, these authors suggest giving patients the option to participate in PRP studies with standardized protocols, to better understand the safety and efficacy of PRP. [85]

Multimodal therapy

In a study by Alizadeh et al that randomized 90 patients to receive oral pentoxifylline, intralesional verapamil, or both for up to 6 months, all 3 groups showed reduction of curvature and plaque size, but the patients who received combination therapy showed better recovery from ED and reduction of pain than those receiving either agent alone. [86]

Paulis et al conducted a case-control study of PTX in combination with other antioxidants in 307 patients with early-stage PD. Patients were divided into two treatment groups (group A, n=112; group B, n=94) and a control group (group C, n=101) of patients who refused treatment. Both treatment groups received 6 months of therapy with oral PTX 400 mg twice a day, propolis 600 mg/d, blueberry (vaccinium myrtillus) 160 mg/d, vitamin E 600 mg/d, and topical diclofenac sodium 4% gel twice a day. Group B patients also received PTX 100 mg, injected close to but not within the penile plaque using a 30-gauge needle, twice a month for 6 months. [87]

After 6 months, all the patients in group A showed a reduction in plaque volume, by an average of 46.9%. In group B, 79.7% of patients showed a reduction in plaque volume, with a mean reduction of 24.8%. None of the patients in group C showed a reduction in plaque volume. An increase in plaque volume was observed in none of the group A patients, in 5.3% of group B, and in 98.01% of group C. Significant reduction in penile pain and penile curvature and improvement in ED was noted in groups A and B compared with group C. Of the study patients receiving oral PTX, 12% noted some degree of adverse effects and 5% developed significant adverse effects that required discontinuation of therapy. [87]

This study found benefit in treating patients early in the course of PD and suggested that penile calcification may improve with therapy. [87]   Limitations of this study include the lack of long-term follow up after therapy and the lack of randomized controls. These issues, along with the adverse effect profile, have limited the use of this therapy to date.

A review by Chung and Yafi concluded that a combined approach that includes oral agents, intralesional agents, mechanical devices, and/or psychosexual therapy is likely to be more effective than any monotherapy. These authors call for larger, multicenter clinical trials with uniform protocols to provide more definitive data on treatment choice. [88]

External vacuum and other mechanical devices

External vacuum devices have been used to attempt to stretch the scarred areas through mechanical means. The patient is instructed to apply the vacuum cylinder and inflate it to maximal tolerable pressure for 10-15 minutes. No tension ring or band is applied. This procedure is repeated once or twice a day for several months. In a small series of 12 patients, 4 patients noted significant curvature improvement, 2 reported slight improvement, and the rest showed no clear benefit, although none demonstrated progression of the curvature. Leslie has suggested that this mechanical approach might work better if supplemented with colchicine or other medical antifibrotic therapies. [89]

Levine and Newell reviewed the use of the FastSize Medical Extender in the treatment of PD. [90] This mechanical device uses controlled periodic stretching of the flaccid penis to extend the length and, in the case of PD, to hopefully straighten the curvature of the penis. They found that significant (10°-45°) improvement in curvature could be achieved in small clinical trials and recommended that larger-scale trials using this device are justified. The long-term benefits and limitations of this new device are pending further trials.

Gontero et al investigated a similar penile extender, the Andropenis (Andromedical, Madrid, Spain), in a phase II prospective study of 15 patients. [91] Men with stable PD, mild penile curvature (not exceeding 500), and mild to no ED were studied. They were required to wear the device for at least 5 hours per day for 6 months. This device provided only minimal improvement in penile curvature (average 31º at start to 27º at end). The mean stretched penile length (SPL) increased by 1.3 cm over the study period, which is probably why the satisfaction rate was favorable. This therapy may be beneficial in selected patients with minimal curvature and little to no associated ED.

A review by Campbell et al of next-generation penile traction devices and updated treatment protocols concluded that the main reason the initial protocols were less successful is that they required a significant daily commitment of application, ≥4 hours/ day, to result in a signifncalt inprovement in curvature and/or SPL. This resulted in the weak recommendations noted the international guidelines. Since the original products and studies were reviewed, modifications have been made in both the design and protocol. [92]

The PeniMaster PRO device (MSP Concept, Berln Germany) uses a vacuum-based glans fixation mechanism to improve penile glans comfort. Moncada et al found this device to be better tolerated and effective in reducing penile curvature and increasing SPL significantly. [93] The device was used for 3-8 hours daily for 3 months to achieve this result.

Ziegelman et al reported on the use of the RestoreX apparatus utilizing a modified protocol with a shorter duration of daily use. [94] This device differs from prior ones in that the penile clamp is wide and flat, there is a counter-bending mechanism, and dynamic adjustment of the device is possible, allowing continuous traction without dismantling. In their study, which included men with curvature > 30º, SPL ≥ 7 cm, and no severe diabetes mellitus, 63 men used the device for 30 minutes 1-3 times a day for 3 months, and 27 untreated men served as controls. Assessment at 3 months revealed significant reduction in curvature of 18% and significant increase in SPL of 1.5 cm and in IIEF scores of 4 points. No severe adverse reactions were noted.

A systematic literature review of penile modeling in PD by Krishnappa et al acknowledged the innovations in design and protocol for penile traction devices (PTD) since the last guidelines update, especially with regard to the RestoreX device discussed above, but concluded that "specific recommendations regarding penile modeling in PD cannot be provided due to limited evidence available." The authors recommended more randomized clinical trials, larger samples, using validated assessment tools and longer follow-up. They also made a case for updating of guideline recommendations regarding the use of PTD, in view of recent improvements in design and protocol. [95]

Low-dose radiation therapy

Another nonsurgical approach to treating PD is the use of low-dose radiation therapy. Incrocci et al reported the results of a retrospective analysis, by mailed questionnaire, of 197 patients who received this treatment from 1982-1997; 106 patients responded to the questionnaire. [96]   However, the mean follow-up period was only 3 months. Penile pain was reported to be diminished or absent in 83% of men, and 23% reported decreased penile deformity. The authors also noted that almost half the men were impotent after treatment, and 29% had undergone surgery to correct their penile curvature. The etiology of the ED in these patients remains unclear.

Mulhall et al reported on the irradiation of cultured cells from Peyronie plaques and from neonatal foreskin. [97] These authors found that all plaque-derived fibroblasts that were irradiated with 5 Gy demonstrated significant elevations in levels of basic fibroblast growth factor and platelet-derived growth factor AB compared with the nonirradiated cultures. The neonatal foreskin cultures did not demonstrate this finding. The authors concluded that their data suggest irradiation may promote fibrosis in persons with PD by possibly increasing the production of fibrogenic cytokines.

Prospective multicenter studies with longer follow-up care are necessary to identify the potential efficacy and long-term adverse effects of this treatment before it can be recommended.

Summary of nonsurgical therapy

In general, the therapies reviewed are best suited to early PD, before the development of a stable or calcified plaque. Assessing the therapeutic response to any of these interventions is difficult without placebo-controlled studies, as has been reflected in the reviews cited above.

In general, the oral and topical methods are likely to be of value with less chance for adverse effects, but some agents such as PTX require further assessment in this regard. The intralesional techniques have the disadvantage of requiring recurrent penile injections. These can be painful and are associated with local adverse effects. The transdermal methods appear to offer the best of both worlds in that they allow for greater delivery of the agent directly to the site while eliminating the trauma of injection. Whether or not these methods will allow enough agent to penetrate the plaque to make a significant difference when compared with a blinded placebo control remains unclear.

At the present time, CCH remains the only FDA-approved intralesional medication for the treatment of PD. Updated penile lengthening devices and treatment protocols are have shown promising results. Their acceptance as single-product therapy or as part of a multimodal treatment protocol awaits further assessment and review of published results.

When these therapies fail or when the plaque becomes calcified, surgical intervention usually becomes necessary for patients who are sexually debilitated by PD.


Surgical Therapy

Before considering surgical intervention for PD, the clinician should make sure the patient meets all of the surgical criteria. The type of surgery chosen, to a large extent, depends on whether the PD is associated with ED. It also depends on the particular characteristics of the individual plaque. [98]

If the plaque is located distally and the angulation is not very severe, a plication procedure can be offered. This operation, usually performed through a circumcising incision, is best suited for a man with a large penis. The ease of the operation and its large chance of being successful must be weighed against the almost universal resulting loss of some penile length. The amount of loss is usually approximately 1 cm.

Greenfield et al performed a retrospective analysis of 102 of 154 men treated with penile plication for penile curvature. [99] Patients were contacted via questionnaire for follow-up. The mean duration of follow-up was 29 months. Ninety-nine percent of men reported a straight penis after surgery. The mean loss of penile length was 0.36 ± 0.5 cm with a range of 0-2.5 cm. The authors identified 3 factors that were associated with greater postoperative loss of penile length: larger preoperative penile length, greater preoperative curvature, and a ventrally placed curvature.

When the penile length or the patient's preference precludes the use of penile plication and if the patient retains erectile ability, then an incision or excision of the plaque can be considered with grafting to reconstruct the tunica albuginea. Although this operation has the advantage of allowing good reconstruction of the penis, potential problems exist. If the plaque is under the dorsal neurovascular bundles, penile anesthesia can result after dissection. Mobilization of the neurovascular complex is often technically difficult in the event of dorsal fibrosis.

The ideal graft material, which should be durable while elastic and tough but flexible, has not yet been identified. Lue and El-Sakka have used venous patches fashioned from the deep dorsal and the saphenous veins. [100] El-Sakka et al reported on the results of their technique in 113 patients observed postoperatively for as long as 18 months. [101] In 96% of the men, the penis became straight; in 94%, no penile narrowing occurred; and, in 83%, penile length was believed to be the same or longer after the operation. Of those men who were potent before surgery, 83% noted the same or better function after the operation. A lasting change in penile sensation was noted by 10%, but 92% were satisfied overall.

Several other novel "off-the-shelf" substances have been used for patches (eg, dermis, tunica vaginalis, temporalis fascia, foreskin, silastic material, Gore-Tex, Dacron). The results have not been as impressive as those reported by Devine and Horton, Treiber and Gilbert, Fournier et al, Ganabathi et al, Krishnamurti, and Yachia et al. [102, 103, 104, 105, 106, 107]

Other investigators have reported results using saphenous grafts, and these results were not as good. Montorsi et al reported on 50 men who were observed for a mean of 32 months. [108] Complete penile straightening was reported in 80%, and penile shortening was noted in 40%.   et al found the technique to be successful for straightening the penis in 15 of 20 men with a mean follow-up period of 13 months. [109] However, these investigators incised the plaque without complete excision.

It appears that incision of the plaque without excision has become the preferred method. Arena et al used a combination of plaque incision and contralateral tunical plication in 24 men. [110] After a mean follow-up period of 24 months, one man had persistent curvature. Significantly, 12 (50%) of 24 men reported penile shortening after surgery. Lue and El-Sakka have reported on a technique to lengthen a shortened penis caused by PD by means of circular venous grafting combined with daily penile stretching by means of a vacuum erection device in 4 men. [111] Although results with this technique are interesting, further testing with a larger cohort is necessary before it can be recommended.

For men with severe compound curvature, Chow et al reported satisfactory outcomes with plaque excision and grafting supplemented with tunica albuginea plication (TAP) when needed to achieve functional straightness (< 20°). Compared with men treated with plaque excision and grafting alone, those who underwent supplemental TAP showed no increased risk of loss of penile length, recurrent curvature, decreased penile sensation, or erectile dysfunction. [112]

In a critical review of the surgical treatment of PD, Kadioglu et al also addressed penile-straightening procedures. [113] These authors stressed that indications for surgical intervention should include (1) symptom duration of at least 12 months, with stability in those symptoms for 3 or more months, and (2) a degree of curvature and/or narrowing that interferes with sexual penetration. Before proceeding with surgery, they recommmend assessing concurrent ED and penile length, and conducting a realistic discussion of patient expectations and likely results. The discussion should address the fact that the patient's penis will not return to exactly the way it was before the onset of his symptoms, no matter what intervention is taken.

The authors present an algorithm for surgical treatment. They recommend a tunical shortening procedure (eg, Nesbit) when the erectile function is good, the curvature is simple and 60° or less, and the penis does not have a significant hourglass or hinge-type deformity. If the patient retains erectile capability but has a complex curvature or one that is greater than 60° or if he has erectile instability due to an hourglass or hinge deformity, a tunical lengthening procedure (eg, incision with graft) should be considered.

If the patient is found to have both ED and PD, then implantation of a penile prosthesis with penile remodeling/reconstruction appears to be best option. The authors present a review of the results of various plication techniques and appear to favor the technique of plication without incision into the tunica [114] and the 16-dot method of Gholammi and Lue. [115] These techniques are easy to perform, involve minimal dissection, require less experience, and yield good satisfaction rates (up to 93%) in achieving a straight penis. The main drawbacks include penile shortening in more than 40% of men and recurrence of curvature in 15% in men.

When a lengthening procedure is indicated, Kadioglu et al [109] agree that the plaque incision described by Lue and El-Sakka [100] is preferred over excision. If the curvature is dorsal, they prefer to expose the plaque through the bed of the excised (and preserved) deep dorsal vein. The neurovascular bundle is dissected from medial to lateral. In this way, the plaque can be exposed and the length of the neurovascular bundle can be restored with a decreased risk of injury to these structures. They contrast the H-shaped incision with the tripod-shaped incision proposed by Ejydio et al. [116]

The authors also discuss the optimal graft material. The vein patch is the most common and has distinct advantages, such as low cost, no foreign-body risk, good elasticity, and a thin wall, allowing for revascularization and minimizing the chance of graft contraction or ischemia. The vein patch is also conducive to reformation of the tunica albuginea over the patch site. Drawbacks in using a vein patch, which is usually harvested from the saphenous vein, include the need for a second incision to harvest the vein. This obviously lengthens the operative time. As with other grafting procedures, problems with bulging at the graft site, hourglass deformity, pain, or numbness may occur.

While short-term straightening rates are satisfactory, longer-term results diminish, with 5-year satisfactory rates reported to be around 60%. [108] Remember that this procedure is indicated in men with significant curvature and/or deformity and that it offers the chance to restore some of a patient's lost penile length.

Among the alternatives to vein grafts, allograft tissue currently appears to be superior to synthetic material. The latter can stimulate significant postoperative inflammatory responses and increase the chances for recurrent curvature. The alloplastic tissues most commonly used include cadaveric or bovine pericardium or cadaveric fascia lata. These tissues are treated to create an acellular matrix that retains tensile strength while minimizing the risk of immune reaction, antigen exposure, and host infection. The matrix allows host tissue to grow in and subsequently replace the graft. Kadioglu et al noted that the use of an allograft for lateral curvature was more likely to be associated with residual curvature postoperatively. [117]

Kalsi et al reported on the use of human-derived treated fascia lata in a small group of men with an average deformity of 67° (range, 20-90°). [118] In this prospective study, a transverse I-shaped incision was used. The resultant defect is narrower than that created with the typical H-shaped incision, and 1-3 grafts are required per patient. The authors report excellent or satisfactory results in 13 of 14 men at a mean of 31 months (range, 17-37 mo) postoperatively. The penis was completely straight in 11 of 14 patients. Penile shortening was avoided in 10 of the 14 patients, while the remaining 4 had penile shortening of greater than 1 cm. One patient developed ED after surgery. These authors noted results similar to those achieved with saphenous vein grafting but without the extra operative time, morbidity, and second incision required for vein harvesting.

Taylor and Levine reported on the long-term results in 142 men with PD treated with either tunica albuginea plication (TAP) or partial plaque excision with pericardial graft (PEG). [119] The participants were observed for an average of 72 months after TAP and 58 months after PEG. Both procedures were associated with a small average length gain in the flaccid stretched penis over time (TAP, 0.6 cm; PEG, 0.2 cm). However, a significant number of men showed loss of rigidity after the procedures (TAP, 19%; PEG, 32%). Even in the hands of these experienced surgeons, 31% of all patients noted decreased sensation postoperatively. Nevertheless, 82% of patients who underwent TAP and 75% of those who underwent PEG were satisfied or very satisfied after the procedure.

Two important lessons can be learned from this study. First, it may be better to recommend implantation of a penile prosthesis in patients with mild ED associated with PD, to maximize length and minimize further deterioration in rigidity. Secondly, it is imperative to have an informed discussion with the patient before treatment so that he can have a reasonable expectation as to the results of intervention.

When ED that is not amenable to medical intervention accompanies penile curvature, counsel the patient for implantation of a penile prosthesis at the time of correction of the angulation. Either a semirigid or an inflatable prosthesis can be used. The use of a semirigid prosthesis usually allows for reasonable straightening of the shaft, but it has a poor cosmetic result. The erect penis is sometimes difficult to conceal. Most men desire an inflatable prosthesis for a better cosmetic result.

If the prosthesis alone is not enough to straighten the penis, then penile remodeling can be attempted, as described by Wilson and Delk. [120] This involves manual and forcible bending of the shaft in the direction opposite to the curvature with the prosthesis inflated. Before this is performed, the tubing from the cylinders must be clamped with a rubber-shod clamp to protect the pumping mechanism of the prosthesis. A characteristic crackling or snapping sound is usually heard with successful attempts.

When remodeling is unsuccessful, the tunica can be incised through the plaque with one or more small incisions. If the penis is still angled, then it will likely be necessary to excise the area of plaque and replace it with a graft. Hellstrom and Reddy reported on the use of processed cadaveric pericardial tissue to accomplish this in 11 men. [121] Of these, 8 men were treated with excision of plaque and placement of pericardial graft, while the other 3 men also received a penile prosthesis. These authors reported resolution of penile curvature in all patients with a mean follow-up period of 14 months.

The choice of prosthesis can make a difference in the ultimate outcome. The American Medical Systems (AMS) Ultrex cylinders should not be used because these rely on an intact tunica albuginea for their rigidity. The Mentor Alpha 1 cylinders are more rigid and can be used for remodeling and for reconstruction but will herniate through a large defect in the tunica. The AMS CX cylinders are best suited for reconstruction in this population because they expand only to a predetermined width, regardless of whether they are surrounded by an intact tunica. They allow remodeling of the penile shaft and/or tunical incision with or without grafting in most cases.


Preoperative Details

Before proceeding with operative intervention, the surgeon must confirm that the patient meets all the criteria for PD surgery. Further, a detailed discussion of the procedure, including a description of the procedure proposed, the ultimate goal of the procedure, the risks of the procedure, the chances for success, and the alternative available methods of treatment, is needed. If possible, include the patient's partner in this discussion.

When counseling a patient for any of the surgical interventions, advising him that his penis will not look exactly as it did prior to the development of PD is important. Some residual angling may remain, the penis may look wider, and it will probably be somewhat shorter than before his symptoms started. This conversation is essential so that the patient will have a realistic expectation of the anticipated results. The time spent on this issue before surgery may save considerably more time and frustration on the part of both the doctor and the patient postoperatively.

The anticipated use of perioperative graft material should also be addressed. The best plan is to decide before surgery whether a prosthesis will be used, rather than waiting to make that decision intraoperatively. Many surgeons use a duplex ultrasonographic evaluation of the penile vasculature before surgery; however, this scan is not used universally. Many surgeons ask the patient to shower with an antibacterial soap for 1 or more days prior to surgery, especially if prosthesis placement is anticipated. Systemic broad-spectrum antibiotics are initiated in the immediate preoperative period and continued for 72-120 hours after the operation.


Intraoperative Details

The details of surgery vary because the plaque can manifest in different areas of the shaft. Which particular procedure or combination of procedures will be used is another factor to be considered.

Nesbit excision/plication

When an excision or plication procedure is selected, it is typically performed through a circumcising incision. The subcutaneous tissue and the Buck fascia are dissected and retracted proximally to expose the tunica albuginea with the overlying neurovascular bundles. The patient is given an artificial erection by placing a tourniquet around the base of the penis and injecting saline into the penis through a 25-gauge butterfly needle. Alternatively, an intracorporeal injection of PGE1 may be used just prior to the scrub at the onset of the procedure.

When a full erection is achieved, tissue directly opposite the area of greatest curvature can be either excised or plicated. Excision is performed by removing an ellipse of tunical tissue and suturing the defect in a circumferential manner with interrupted nonabsorbable sutures while carefully avoiding the underlying corporeal tissue and the overlying neurovascular tissue. Plication is performed by placing several parallel rows of 2-0 silk suture through the tunica in a line extending perpendicular to the shaft. The sutures are placed in and out, in and out to plicate, or bunch up, the tunica. Each is placed no more than approximately 5 mm apart. Take care to avoid injury to the neurovascular bundles dorsally and the corpus spongiosum ventrally.

When the sutures are tied, the penis should become straighter. If necessary, another row of sutures is placed parallel to the first row. The wound is irrigated and closed without a drain. A Coban dressing can be applied for 4-6 hours to minimize postoperative bleeding.

Ralph discussed the variations of penile-straightening procedures such as the Nesbit operation [122] and compared this with the recent modification of penile plication without incision as popularized by Essed and Schroeder [114] and Ebbehøj and Metz. [123] Although the plication alone is easier and requires less dissection, it carries a higher rate of PD recurrence. Ralph believes that this is due to reliance on the strength of the suture alone for the repair to be successful. Despite this problem, the plication technique appears to be well-suited to dorsal and ventral curvatures since it requires minimal dissection of the dorsal neurovascular bundle and the corpus spongiosum.

A modification of this plication, described by van der Horst et al, includes the use of parallel incisions in the tunica albuginea, perpendicular to the shaft and at the point opposite the greatest curvature (see images below). [124] These authors then used an inverted stitch technique to minimize pain caused by the sutures. The proximal side of the proximal incision is sutured to the distal side of the distal suture over (and burying) the intervening strip of tunica. They found that polytetrafluoroethylene sutures were associated with less discomfort and were less likely to be felt by the patient than were polypropylene sutures. In 55 patients who began with a curvature of greater than 20° and who did not have preoperative ED, anatomical straightening was achieved in all postoperatively, and 90% were able to achieve intercourse (compared with 62% preoperatively); 74% noted some degree of penile shortening.

Skin is incised through previous circumcision and Skin is incised through previous circumcision and retracted. Artificial erection is achieved with injection of normal saline via butterfly with tourniquet at base of penis. This demonstrates 45° curvature of the penile shaft to patient's left.
Buck's fascia has been incised along the convex, r Buck's fascia has been incised along the convex, right side of the penile shaft to expose the tunica albuginea. The right dorsal neurovascular bundle has been dissected from the tunica albuginea (left side of figure). Parallel incisions have been made through the tunica albuginea to allow plication of the convex side of the shaft.
The isthmus of tunical tissue has been buried by s The isthmus of tunical tissue has been buried by suturing the proximal side of the proximal incision to the distal side of the distal incision. Another set of incisions were placed distal to the original set for further correction of the curvature. These were then sutured in a similar fashion. The second suture line can be seen closer to the corona.
Buck fascia and the skin layer have each been reap Buck fascia and the skin layer have each been reapproximated. A repeat artificial erection demonstrates correction of the curvature. The penis is then dressed with Xeroform gauze and Coban dressing.

In a follow-up study, van der Horst et al reported that, from a quality-of-life standpoint, 88% of patients and 78% of their partners were satisfied with the operative outcome. [125]

Plaque incision/excision and graft placement

If plaque incision/excision and graft placement are planned, the dissection becomes a little more difficult. If the plaque and curvature are located distally in the shaft, a circumcising incision can be used. After exposing the shaft, proceed with the dissection of the plaque to incise or remove all affected tissue.

If a synthetic graft is to be used, it is made ready. If the deep dorsal and saphenous veins are to be used, these are harvested and prepared for insertion. All extraneous tissue is removed from the venous graft, and the typical long, narrow piece of tissue is cut carefully into shorter strips, which are sutured together to fashion a suitable patch. Then, this is sutured into place using 4-0 or 5-0 nonabsorbable sutures. Importantly, remember that the graft will appear larger before it is sewn than afterwards.

If the plaque is located in the proximal shaft, then a penoscrotal incision is preferred. This incision starts at the base of the penis and continues proximally along the median raphe for approximately 2 inches. It allows excellent access to the proximal penile shaft and is best suited for ventrally located plaques. If necessary, the shaft can be degloved by stripping the skin off the penile shaft superficial to the Buck fascia in a distal fashion and leaving it attached at the level of the corona. This approach is also useful if more than one plaque is present. An alternative approach, when multiple plaques are present, is to use more than one incision to achieve access to all plaques. In choosing the correct approach, remember that the goal of surgery is to leave the patient with a straight penis while preserving the maximum amount of normal sensation and erectile function.

After access has been obtained by one of these approaches and the Buck fascia has been dissected clear, care must be taken to preserve the neurovascular bundles in dorsal dissection and the urethra and corpus spongiosum in ventral dissections.

In cases in which exposing the entire penile shaft is necessary, Devine et al (1992) reported on the use of a 2-incision method to deglove the shaft. [21] One incision is made lateral to the base of the penis and extended down to the scrotum. The second is a circumcising incision through the scar of a previous circumcision. The skin can be dissected free from the shaft, and the penis can be retracted free from the skin, to be replaced at the end of the dissection.

Whenever dissection is anticipated in the region of the urethra or if a prosthesis is used, place a Foley catheter and keep it in the sterile field by clamping the end. This can be removed the following morning if the dissection proceeds without complications.

Hauck et al attempted a novel approach to remove the plaque, using a dental drill and carbide bur. These authors attempted to thin the tunica at the plaque site with the bur. [126] They then made a small transverse incision in the plaque and placed a graft fashioned from autologous deep dorsal vein. They treated 13 men with severe curvature (mean preoperative curvature of 73°) and were able to achieve a straight penis intraoperatively in all patients. However, their postoperative results were disappointing. The curvature recurred in 8 of 13 men, penile shortening (mean, 3.3 cm shorter) occurred in 7 of 13 men, and decreased rigidity during intercourse was reported in 4 of 13 men after the procedure. These results caused the authors to abandon this procedure.

Hatzichristou et al combined a Nesbit plication with a corporoplasty. [127] A standard Nesbit plication was used at the point opposite to maximal curvature. The resulting ellipse of tunica albuginea was then used as a free graft and sutured to the defect created by excision of the plaque on the opposite side of the shaft. With this method, penile shortening could be minimized and the ideal reconstructive tissue (ie, autologous tunica albuginea) could be used. The authors reported on 17 men so treated with mean follow-up of 39.5 months (range, 18-62 mo). All patients reported successful penile straightening and maintenance of their preoperative erectile function. Forty-seven percent had objective penile shortening, although only 11% considered this significant. Larger studies on this interesting combined treatment are needed.

Adeniyi et al reported results with the Lue procedure of plaque excision and grafting with saphenous vein in 51 patients with a mean follow-up of 16 months. [128] Ninety-two percent reported a satisfactory functional outcome, and 82% had complete straightening of their penises. However, 35% reported penile shortening, 12% had difficulty with intercourse, and 8% developed ED after surgery.

In an innovative approach, Bella et al reported on a minimally invasive, intracorporal incision of the Peyronie plaque using a 5-mm triangular blade introduced under the tunica albuginea. [129] The technique was used in 23 men with a median deformity of 60° (range, 30-90°), a palpable plaque shorter than 2 cm, and a stable painless curvature. Significantly, 21 of 23 patients had a dorsal curvature, and 19 of 23 had normal preoperative erectile function.

The main advantage of this technique is that it can be performed through one or two 1-cm lateral corporotomy incisions and requires minimal mobilization of the neurovascular bundle over the plaque, a distinct advantage in treating dorsal plaques. However, 12 of 17 men with preoperative curvature of more than 60° required ventral plication sutures to achieve full straightness. They reported that the presence of plaque calcification did not prevent successful release of curvature. Initially, 21 of 23 men were found to have successful correction of penile curvature, defined as less than 10° of residual curvature.

A telephone survey of 20 available patients at a mean of 25 months after surgery found that 11 (55%) men were able to achieve rigidity sufficient for intercourse without additional therapy. Another 5 (25%) men required sildenafil or PGE1 to achieve satisfactory function. Seventeen (85%) men reported penile shortening that did not adversely affect erectile function, and one reported partial glans hypoesthesia.

While this technique is easier than incision and grafting, it is more difficult than plication alone and yields similar results. Nevertheless, this approach may be beneficial in men with significant dorsal curvature. Further long-term follow-up with a larger patient population is needed.

Sansalone et al reported the use of the Egydio technique on 157 patients with PD that had been stable for 6-12 months. [130] Patients were followed postoperatively for 12-24 months (median, 20 mo). Mild residual curvature was reported in 12%, and glans hypoesthesia was reported in 3%. The authors reported that "all patients recovered their ability to penetrate with no difficulty."

Contemporaneously, Flores et al analyzed 56 men with PD for 22 ± 9 months who underwent plaque incision and grafting (PIG) using either H-type incision or Egydio technique. [131] Although all men had rigidity satisfactory for penetration preoperatively, 46% reported a 6 point or higher decrease in IIEF score after surgery. This reduction was predicted by larger baseline curvature, use of the Egydio plaque incision technique, older patient age, and the presence of venous leakage at baseline evaluation. The authors use these data to discourage older men, those with venous leakage and men with significant curvature (>60%) from having the PIG procedure.

Although PIG techniques offer the benefit of penile straightening with potential return of penile length, this does not seem to be the usual result long term. Chung et al performed a retrospective database review and third party survey of all of their patients who underwent reconstruction with grafting for PD between 1999 and 2005. [132] All patients underwent PIG with dermal grafts (n = 20), Tutoplast grafts (n = 33), or Stratasis grafts (n = 33). Eighty percent of plaques were dorsally located. Average penile curvature was 71.7 º (30-160 º). At 6 weeks after surgery, 60% of dermal, 100% of Tutoplast, and 86% of Stratasis patients described resolution or significant improvement in penile curvature.

Forty-six (53%) out of 86 patients were contacted and surveyed 60-120 months after reconstruction. At that time, recurrence of curvature was reported by 50% of dermal, 87% of Tutoplast, and 76% of Stratasis patients. Further, 17%, 17%, and 29% also reported penile shortening, respectively. Of all patients surveyed, 13% reported altered penile sensation, and 4% reported glans hypoesthesia. Also noted was worsening of IIEF-5 scores in all patients who received PIG and were surveyed at least 5 years afterwards. Finally, more than 65% of the surveyed patients reported dissatisfaction with the surgical outcome.

These authors recommend that the simultaneous implantation of a penile prosthesis with PIG be at least considered in men who have severe or complex penile deformity, even without concurrent ED. This approach can correct penile curvature, maintain penile length and prevent the otherwise likely development of ED that the authors reported.

Shaeer described a novel approach to treat patients with combined ED and PD who presented with stable and severe deformity of the penis. [133] Sixteen men with penile curvature, hourglass deformity or both were treated with a combination of endoscopic plaque incision from within the corpora cavernosa and simultaneous implantation of a penile prosthesis. All patients had complained of loss of penile length before surgery.

After identifying the deformity via an artificial erection and measuring the dorsal length of the penis, the author used a peno-scrotal incision and ventral corporotomies to enter, dilate and measure the length of each corpus cavernosum. Transcorporeal incision (TCI) was then performed using a cystoscope and a cold knife or a diathermy knife electrode. The cystoscope was introduced into the corpus cavernosum through the corporotomy. This was performed at the point of maximal curvature. A partial thickness incision was the goal.

To minimize the chance of infection, the author used systemic perioperative antibiotics and intraoperative antibiotic irrigation. He also added bacitracin to the cystoscopy irrigation solution. The cystoscope and corporotomy set were sterilized with ethylene oxide and the author recommended reserving a corporotomy set to be used exclusively for this procedure.

A snug dressing was applied to the shaft at the end of the procedure and the prosthesis was left in the erect position for an average of 4 weeks.

No patients reported sensory deficit or residual curvature after an average of 14 months follow-up. No postoperative infections were noted. Post-TCI penile length gain averaged 2.1 cm. All patients expressed satisfaction with the results, but the author did not use a scale to measure pre and post procedure satisfaction.

This is a new approach to correction of penile deformity from PD with associated ED. The author reports excellent results in this small study with limited follow-up. If these results are supported in larger studies then this technique should be considered in patients with severe deformity and concurrent ED.

Placement of a penile prosthesis

In patients with both PD and ED, the physician should consider treatment that addresses both of these problems simultaneously, such as the placement of an inflatable penile prosthesis. To be a candidate for this treatment approach, the patient should have a stable plaque, poor sexual function, and associated ED with poor response to oral agents such as sildenafil. This alternative offers the patient the ability to achieve and maintain rigidity while straightening the penis. It minimizes penile shortening.

When the decision has been made to use a prosthesis, either with or without a graft, the preferred approach is the penoscrotal incision. This allows easy access to the corpora cavernosa. It also allows access to the scrotum for placement of the prosthetic pump and to the retroperitoneum through the inguinal canal for placement of the reservoir.

The penis can be degloved to allow incision/excision of a plaque, with or without grafting. The alternative approach is the infrapubic incision. While this allows for direct placement of the reservoir, it does not allow comparable access to the corpora cavernosa. As a result, cavernosal dilatation may be difficult, especially in men with corporeal fibrosis from PD. In either of these approaches, additional circumferential incisions or a circumcising incision can be added to improve access to a particular plaque.

If a penile prosthesis is used, one can attempt to remodel the penis over the inflated prosthesis. After the cylinders are placed within the corporeal bodies, they are fully inflated. The tubing that connects each cylinder to the pump is then clamped with rubber-shod clamps. This protects the pump mechanism from damage. Next, the penile shaft is bent forcibly in the direction opposite to the point of maximum curvature. As the shaft is deformed, a cracking sound may be heard, which represents disruption of the fibrous plaque. After this procedure, inflate the cylinders further and assess the straightness of the penis. The remodeling can be attempted more than once, but take care to not place an excessive amount of pressure on the distal tips of the corpora with the distal tips of the prosthesis because this may predispose the patient to extrusion of one or both cylinders through the corporeal tip and out the urethra.

If remodeling is not successful, then mark the area of plaque and/or curvature with an intraoperative marker. If a Mentor prosthesis is being used, it must be removed from the corporeal space before incision or excision of the plaque is attempted. If an AMS CX prosthesis is used, the surgeon can allow the cylinder to remain inside the corporeal body as long as cautery and not a scalpel is used on the plaque. The AMS silicone prosthesis will not conduct the cautery electric current, while the Mentor isomer prosthesis will conduct the current and will be damaged or destroyed during plaque removal.

If the plaque(s) is small, then incision may be sufficient. This is performed by making circumferential incisions in the tunica albuginea at the level of each plaque. If these are small, placing a graft or closing the resultant defects is not necessary. They may be left open and covered with the Buck fascia during closure. On the other hand, if the plaque is large, a large H-shaped incision can be used to open up the plaque. This incision is made directly over the plaque and is extended until the penile shaft is straight. Such an incision usually requires placement of a graft to close the tunica albuginea. This will guard against aneurysm of the tunica and/or extrusion of the prosthesis.

If the plaque is located dorsally, elevating each neurovascular bundle off the tunica albuginea may be necessary to allow access to the plaque. This can be accomplished by dissection parallel to the penile shaft while elevating each neurovascular bundle. One must be careful in this area because damage to these structures results in loss of penile sensation. On the other hand, if the plaque resides ventrally, the operator may have to separate the corpus spongiosum from the tunica albuginea before attempting to remove the plaque. This dissection can be tedious and can lead to an increased possibility of urethral injury.

If the patient has not been previously circumcised and a circumferential incision is selected, performing a circumcision after reconstruction is prudent in order to prevent ischemic skin damage secondary to mobilization. These dissections can be tedious because the plaque can extend into the cavernosal tissue.

Montorsi et al reported on 10 men with severe penile curvature, fibrosis, and shortening due to PD. [134] They were treated with several cavernosal-relaxing incisions and insertion of an inflatable prosthesis. Average penile length increased by 2.3 cm in the flaccid penis and 3 cm in the erect penis at 6 months after surgery. Nine of 10 men reported successful intercourse with better erections and straight penises.

Mulhall et al reported on the treatment of 36 men for combined PD and ED with a penile prosthesis and assessed the need for intraoperative adjuvant maneuvers. [135] The authors found that, in all men with preoperative curvature of less than 30°, placement of a prosthesis and full inflation of it was sufficient to result in a straight penis. In men with a curve greater than 45°, 86% required plaque incision to achieve a straight penis. Only 5.5% required a graft, and these men had curvature of greater than 60°. These authors used the Mentor Alpha 1 prosthesis in all men.

Kadioglu et al found that a penile prosthesis alone or with penile modeling could result in a straight penis in up to 75-85% of men. [113] An inflatable prosthesis, such as the AMS-CX or the Mentor Alpha 1, is preferred over a semirigid prosthesis or a tunica-expanding prosthesis, such as the AMS Ultrex model. When penile deformity persists, simple incision of the plaque without grafting can increase the success rate to 95%. Incision of the plaque with grafting over a prosthesis is usually reserved for men with curvature of more than 60° or a dorsal plaque that is longer than 4 cm.

When the curvature is great enough that implantation of an inflatable penile prosthesis would still result in real or perceived loss of penile length,  one may consider a length-restoring procedure such as the sliding technique described by Rolle et al. [136]  In this technique, long parallel corporotomies are performed at the time of prosthesis placement and used to stretch the peis. The defects are grafted at the same time. This operation is complex and poses significant risks, so it should be attempted only by surgeons with extensive experience in treating the sequelae of PD.


Postoperative Details

At the end of the procedure, the penis is usually wrapped with Coban dressing over gauze. Remove this dressing after 4-6 hours and replace it with a sterile, nonconstricting dressing. The Foley catheter is removed on the following morning, and the patient is sent home with a prescription for oral antibiotics. He is seen for follow-up care in 1 week.

Lue and El-Sakka institute daily use of a vacuum erection device for 6 months starting 1 month after reconstruction of foreshortened penises. [111] This technique can also be used in men who undergo plaque incision or excision without prosthesis implantation.

Encourage men who have the concurrent placement of a prosthesis to inflate the prosthesis daily as soon as this is tolerable. It usually takes 4-6 weeks for the pain and edema to subside enough to allow the prosthesis to be inflated.



Follow-up care varies depending on the type of treatment used. When a specific medical treatment is used, plan follow-up care for regular intervals after the intervention is completed to evaluate the results and to check for progression of symptoms. A reasonable routine is every 3 months until the patient stabilizes.

Surgical intervention requires closer follow-up care initially to ensure that the patient heals well from the surgery. Normal surgical practice should guide follow-up care during this phase. Afterward, the patient should continue to be observed regularly to assess the results of the surgery and to identify any recurrence of symptoms. This can be performed at 3-month intervals for the first year and yearly after that. These guidelines may have to be altered markedly in any individual situation based on the result of the intervention, any progression of the PD, and the level of anxiety and frustration of the patient.




Complications from the treatment of Peyronie disease (PD) depend on the particular treatment used.

Oral therapy has little chance of resulting in complications. Medications that are injected into the plaque can result in edema or scarring at the site of injection. This can lead to worsening of the curvature and/or penile shortening. Intraplaque injection may rarely result in ulcer formation.

Surgical intervention carries the risks associated with any operation (ie, infection, bleeding, or an anesthesia complication). Incision or excision of a scar may lead to scar reformation with return of the curvature. It may also lead to increased penile foreshortening.

When dissection is necessary under either the dorsal neurovascular bundles or the corpus spongiosum, the chance is always present that these structures might be injured. Damage to the neurovascular bundle can result in permanent anesthesia in the glans and/or portions of the shaft. It can also lead to loss of erections by compromising the corporeal veno-occlusive mechanism. Damage to the dorsal arteries is unlikely to affect penile erections unless it is proximal, at or above the level of the origin of the cavernosal artery. Injury to the corpus spongiosum can usually be repaired with fine absorbable sutures, but the surgeon must take care to not injure the urethra, which it covers. If symptoms persist after a grafting procedure, prosthesis placement is normally not substantially complicated from the prior surgery.

If a prosthesis is implanted, then the patient is subject to all the potential complications associated with this device. Notably, infection can occur, especially because these procedures usually require longer operative times because of their complexity. Perioperative antibiotic therapy is a necessity. Prosthesis malfunction or poor prosthetic fit can also arise, but these should occur with no greater frequency than when a prosthesis is used to treat ED alone.


Outcome and Prognosis

In general, the outcome of treatment of Peyronie disease (PD) can be judged in 2 ways: first, by the degree of improvement in penile curvature and plaque, and second by the return to satisfactory sexual functioning. Either may be the primary goal of an individual patient. The most satisfying results are obtained when the primary goal of the patient is identified early in the course of treatment. The likelihood of achieving these goals is very good if all of the potential interventions listed are included.

The most recent available data have identified some new trends in the treatment of PD, as follows:

  • When oral treatments are used, a combination of colchicine and vitamin E appears most likely to be successful.

  • Topical verapamil alone does not seem to be as effective as when it is used with electromotive drug administration (EMDA) to transport it into the tunica.

Some tenets of treatment remain, as follows:

  • Mild cases of PD (ie, minimal or no pain, the ability to achieve penile erections, curvature that does not prevent intercourse) may improve spontaneously. A trial of conservative treatment with observation and reassurance is indicated.

  • Pain usually resolves with or without treatment and is not a good predictor of successful therapy.

  • Oral or topical therapy should be initiated first, especially in men with unstable plaque.

  • Indications for surgical intervention should include the following: (1) symptom duration of at least 12 months with stability in those symptoms for 3 or more months, (2) a degree of curvature and/or narrowing that interferes with sexual penetration, (3) an assessment of concurrent ED and of preoperative penile length and curvature, and (4) a realistic discussion of patient expectations and likely results. The last should address the fact that the patient's penis will not return to exactly the way it was before the onset of his symptoms, no matter what intervention is taken.

  • Consider penile plication when the erectile function is good, the curvature is simple and 60° or less, and the penis does not have a significant hourglass or hinge-type deformity. Simple plication of the tunica without excision or plication after linear incision appears to maximize results with minimal side effects. Some loss of penile length can be anticipated. Proper patient selection and counseling are necessary to maximize postoperative satisfaction.

  • If the patient retains erectile capability but has a complex curvature or one that is greater than 60° or if he has erectile instability due to an hourglass or hinge deformity, plaque incision with graft placement should be considered.

  • When PD and ED are both present, the best therapy appears to be implantation of a penile prosthesis with modeling or, in men with extreme curvature, plaque incision with or without graft placement.

  • Endoscopic plaque incision combined with implantation of an inflatable penile prosthesis may become a useful tool to treat men with significant curvature requiring dissection of the dorsal neurovascular bundle(s) associated with refractory ED. Further experience with this technique is eagerly anticipated.


Future and Controversies

Preliminary research suggests that stem cell therapy using stromal vascular fraction (SVF) offers promise for the treatment of Peyronie disease (PD). SVF is a mixture of adipose-derived stem cells, endothelial precursor cells, and immune modulatory cells that act synergistically to facilitate angiogenesis and differentiation of epithelial cells. As a result, SVF may promote reconstitution of vasculature and endothelial lining in patients with PD. [137]