Peyronie's Disease

What is Peyronie's Disease

Peyronie's disease (PD) is an acquired, localized fibrotic disorder of the tunica albuginea (the internal penile sheath delimiting the erectile tissue) resulting in penile deformity, mass, pain, and, in some men, erectile dysfunction.

Natural History

We distinguish three stages of the disease: Early active, late active, and inactive. The early (painful erection) and late active stage (onset and progression penile curvature and plaque), usually lasts 12 to 18months. After that, the disease becomes inactive. In this stage, the penile curvature is stable and does not get worse (does not progress).

The active PD can resolve spontaneously, in a minority of cases, without or with minimal curvature and without any impact on sexual life. Others will have stable penile curvature. The treatment depends on the impact on a patient's sexual life.

Symptoms

We distinguish the symptoms of the early active stage, active late-stage and the chronic stable stage of the disease.

Symptoms of the early active stage

The first symptom is a painful erection. It can be variable from little and unremarkable, to severe pain, with an impact on the ability to maintain the erection and on the quality of the sexual life. Some patients avoid sexual intercourse because of pain. In this stage, the patient can feel a hard nodule commonly in the dorsal part of the penis. The penile curvature is minimal or absent.

Symptoms of the late active stage

The patient complains about nodule/plaque, indentation, curvature, deformity, or shortening during erection, as well as sexual dysfunction. These symptoms are usually progressive during all the remaining of the active stage.

Symptoms of the inactive stage

The penile curvature, deformity, or shortening became stable and they will not progress. The resulting stable penile curvature might have no or severe impact on the patient's sexual life because of curvature (penetration impossible) or erectile dysfunction related to the damage of erectile mechanism.

Treatment of Peyronie's Disease

No surgical treatments

The Conservative treatment of Peyronie's disease is primarily focused on patients in the early stage of the disease. Several options have been suggested, including oral pharmacotherapy, intralesional injection therapy, and other topical treatments (Table 1). Physical treatment based on Shock waves or iontophoresis have also been described. While the clostridial collagenase is the only drug approved for the treatment of Peyronie's disease by the American FDA (Federal Drug Administration), no single drug has been approved by the European Medicines Agency (EMA) for the treatment of Peyronie's disease at this time. The results of the research on conservative treatment for Peyronie's disease are often contradictory making it difficult to provide good recommendations. The low quality of the studies is related to uncontrolled studies, a limited number of patients treated, short-term follow-up, and different outcome measures.

Oral treatments

Vitamin E and Colchicine

Vitamin E is commonly prescribed by the majority of urologists at once or twice daily doses of 400 IU because of its wide availability, low cost, and safety [38]. However, the research evidence does not allow to make recommendations. The combination of vitamin E and colchicine (600 mg/day and 1 mg every 12 hours, respectively) in the early stage of disease for 6 months in patients with early-stage Peyronie's disease seems to improve the plaque size and curvature. However, pain relief is less evident.

Potassium Para-aminobenzoate (POTABA)

Potassium para-aminobenzoate is not superior to other oral medications on treating the penile pain, plaque size, and curvature. It seems it can have a protective effect on the deterioration of penile curvature.

Tamoxifen

The results are very conflicting and we cannot make any recommendation.

Acetyl esters of carnitine

The combination of propionyl-l-carnitine with intralesional verapamil seems to significantly reduces penile curvature, plaque size, and disease progression [53].

Pentoxiphylline

Pentoxifylline seems to stabilize or reduce calcium content in penile plaques [56].

Phosphodiesterase type 5 inhibitors (Cialis 2.5 mg)

No well-supported recommendation can be given for PDE5I in patients with Peyronie's disease.

Intralesional treatment

Injection of pharmacologically active agents directly into penile plaques allow a localized delivery of a particular agent that provides higher concentrations of the drug inside the plaque. However, delivery of the compound to the target area is difficult to ensure particularly when a dense or calcified plaque is present.

Steroids

Intralesional steroids are thought to act by opposing the inflammatory milieu responsible for Peyronie's plaque progression. Adverse effects include tissue atrophy, thinning of the skin, and immunosuppression. We cannot conclude with a well-supported recommendation [60].

Verapamil

The studies suggest that intralesional verapamil injections could be advocated for the treatment of non-calcified acute phase or chronic plaques to stabilize disease progression or possibly reduce the penile deformity. Side-effects are uncommon (4%). Minor side-effects include nausea, light-headedness, penile pain, and ecchymosis [68].

Clostridium Collagenase (Xiaflex)

Clostridium collagenase is now approved by the Food and Drug Administration (FDA) for PD in adult men with a palpable plaque and a curvature deformity of at least 30° at the start of therapy. The most commonly reported side-effects are penile pain, penile swelling, and ecchymosis at the site of injection [75]. Of note, CCH is available in the US only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) because of the risks of serious general and penile adverse reactions. CCH should be administered by a healthcare professional only in certified facilities and ensure that CCH is dispensed only for use by certified healthcare professionals [76].

Interferon

Intralesional injections of Interferon α 2b (two times per week for 12 weeks) seem to improve penile curvature, plaque size and density, and pain [78, 79]. Side-effects include myalgias, arthralgia, sinusitis, fever, and flu-like symptoms. They can be effectively treated with non-steroidal anti-inflammatory drugs before interferon injection.

Physical treatments

Topical Verapamil

There is no evidence that topical treatments applied to the penile shaft result in adequate levels of the active compound within the tunica albuginea [80]. Iontophoresis - now known as transdermal electromotive drug administration (EMDA) - has been introduced to try and overcome limitations on the local uptake of the drugs themselves. However, we cannot conclude with well-supported recommendations.

Extracorporeal Shock Wave Treatment (ESWT)

It is a treatment using focused shock waves in the plaque in more sessions. The few studies so far have only shown significant improvement only for penile pain. We have not strong support about the effects on the plaque and on the penile deformation. [87].

Traction devices

The FastSize Penile Extender has been studied and applied as the only treatment for 2-8 hours/ day for 6 months [89]. It seems effective in reducing the penile curvature and allow the patient to avoid the surgery. [90].

Vacuum Devices

The application of vacuum devices follows the same principles as traction devices with the drawback of being non-continuous.

Surgical Treatments

We do surgery in those patients who have their sexual life affected because of difficult or impossible penetration related to the penile curvature. The penile curvature is the result of the early acute stage of the disease which usually lasts 12 to 18 months. The chronic, late stage of the disease, is described when the curvature is stable. At this stage, we do not expect any further changes. Procedures range from the simple straightening penileplasty (Nesbit Procedure) to plaque excision and substitution procedures. Choosing the most appropriate surgical intervention is based on:

  • penile length assessment
  • curvature severity
  • erectile function status
  • patient expectations

According to postoperative penile length, we distinguish shortening and lengthening procedures. A penile prosthesis is an additional surgical option.

Penile Shortening Procedures

Penile shortening procedures include the Nesbit wedge resection and the plication techniques performed on the convex side of the penis. The overall short- and long-term results of the Nesbit operation are excellent. Complete penile straightening is achieved in more than 80% of patients.

Patient selection

A good candidate for this surgery:

  • patient with significant curvature affecting the ability to penetrate
  • curvature, not more than 30 degrees
  • patients who accept 1-1.5 cm penile shortening

Complications

Complications are uncommon (about 10%):

  • Recurrence of the curvature
  • penile hypoesthesia
  • the risk of postoperative ED is minimal

Penile Lengthening Procedures

Tunical lengthening procedures entail an incision in the short (concave) side of the tunica to increase the length of this side, creating a tunical defect, which is covered by a graft (derma, vein and buccal mucosa graft).

Patient selection

  • Curvature more than 30 degrees
  • Patients not accepting excessive penile shortening
  • Patient assessed and normal erectile function

Complications

  • Recurrence of the curvature
  • Erectile dysfunction

Penile Prosthesis

A penile implant (or penile prosthesis) is a medical device that is surgically placed into a penis to produce a natural-looking and natural-feeling erection. In cases of severe deformity, the surgeon can do intra-operative 'modeling' of the penis over the inflated cylinders.

Patient selection

  • Severe penile curvature
  • Other penile deformities related to the plaque
  • Erectile dysfunction

Complications

  • Infection
  • Urethral perforation
  • Prostate extrusion