Treating Peyronie’s Disease – A Contemporary Overview

A wide variety of medications, surgery, and stretching devices and have been used in the treatment of Peyronie’s disease. Even the type of shock waves administered for kidney stones have been tested. Up to the present there has been a lack of consensus among urologists as to what constitutes the optimal approach – partly due to a lack of carefully planned well-executed controlled scientific studies, and partly due to the wide variation in effects from one individual to another. These may range from the penile pain of early inflammation in some to penile shrinkage or curvature due to chronic scarring in others.

Treatment Modalities and Options

  • Medications & Supplements
  • Surgery
  • Devices

Medications and Supplements

To evaluate the results of Peyronie’s disease treatments, we need to know how the disease evolves on its own in the absence of therapy. Understanding this so-called “natural history” provides a basis for comparison of outcomes from various treatment modalities. Even so, the quality of evidence supporting medical (non-surgical) treatments varies tremendously across the spectrum of drugs and agents that have been used.

During the first six months or early phase of the disorder erections can be painful, though about half of patients have minimal or no pain initially. Eventually the pain tends to resolve on its own as Peyronie’s disease enters the second, or chronic stable phase. Unfortunately, bending does not usually follow the same course as pain – in the majority of men, angulation present in the latter stages of Peyronie’s usually persists. Though it is unlikely for bending to worsen or progress after this point, it generally will not resolve spontaneously. Factors associated with a tendency for bending to persist are the presence of Dupuytren’s contractures in the hand, the presence of plaque calcification, and severe angulation (>45°).

Up to quite recently, doctors felt the best results with non-surgical or “medical therapy” could only be obtained during the early phase of Peyronie’s disease, whereas correction of the loss of elasticity and resulting curvature associated with the chronic second stage required surgery. Traditionally medications were employed early on, and later, in those persistent cases with significant loss of sexual function due to penile deformity, surgery was recommended.

This view was based on the mechanism of action of medical therapy: it was intended to reduce the inflammatory response or inhibit the deposition of new scar tissue, but had little if any effect on established or chronic scar. Recent data from clinical trials with collagenase clostridium histolyticum (Xiaflex®) have called the traditional approach to non-surgical therapy into question, having shown statistically meaningful improvement both in curvature and subjective function in men with stable chronic disease of > 1 year duration. While starting treatment early is always a good principle, it appears that for the first time men with longstanding deformity may in many cases expect improvement with non-surgical therapy.

Be informed about your treatment – read the following about medical and surgical treatments for Peyronie’s disease. For further information, feel free to submit questions to Dr. Gelbard in the Peyronies disease forum.

Medications and remedies used “off label” (without FDA approval):

  • VITAMIN E this antioxidant has been widely used in the treatment of Peyronie’s disease since 1948, though scientific evidence on its effect is lacking.
  • POTABA or potassium para aminobenzoate is related to B complex vitamins and theoretically can help the supply of oxygen to inflamed tissues. There is no good placebo – controlled evidence that it is effective in the treatment of Peyronie’s and the high doses usually recommended can cause digestive upset.
  • COLCHICINE is a medication used for many years in the treatment of Gout. It acts against inflammation, and interferes with collagen (scar) synthesis. There is weak evidence for its effects against Peyronie’s in clinical trials. It can cause diarrhea, and should not be used in patients who are on statins (cholesterol-lowering drugs) due to the risk of muscle inflammation.
  • TAMOXIFEN is a non-steroid antiestrogen that may inhibit scar-producing cells. Clinical evidence for use in Peyronie’s disease is weak – it was unable to outperform placebo.
  • ACETYL CARNETINE appears to reduce cellular damage due to inflammation. Clinical trials in Peyronie’s patients have shown minimal effects.
  • L-ARGENINE is an amino acid supplement that is a precursor to a nitric oxide, a neurotransmitter critical for erection, and is thought to inhibit fibrosis or scarring
  • PENTOXYFILLINE improves red blood cell circulation in vascular disorders, and may help to locally reduce scarring following inflammation.
  • VERAPAMIL blocks the delivery of scar tissue precursors into an area of wound healing. Penetration into plaque tissue has not been proven when used as a topical ointment. Injection directly into the plaques has shown varying degrees of success – some clinical trials have shown benefit while others found it did not outperform placebo.
  • ALPHA INTERFERON is a signaling protein that plays a role in human immune responses, by inhibiting the proliferation of cells. It was the first anti-Peyronie’s disease drug to be tested in a multi-institutional clinical trial, where comparison to placebo showed a small effect on curvature reduction. It has a tendency to produce systemic flu-like symptoms.

FDA-approved medication for Peyronies Disease

  • COLLAGENASE CLOSTRIDIUM HISTOLYTICUM (CCH) is a proprietary combination of two enzymes found in cell-free filtrates from cultures of the bacterium Clostridium Histolyticum. This mix of powerful enzymes is highly specific for collagen, the molecular constituent of scar tissue. It is capable of dissolving this scar tissue at normal body temperature and pH, reducing the curving or distorting effect scar creates in the erectile bodies (corpora cavernosa) of the penis. That it is highly specific for collagen and harmless to other structural or circulating proteins, and that it binds tightly and quickly to collagen at the injection site without the tendency to spread through tissues contributes to its safety profile. It has been FDA approved for use in the hand (treating Dupuytren’s contractures) since 2011, and in December 2013 was approved for use in Peyronies Disease. This biologic agent (it is not technically a drug) is in a completely new class compared to the existing therapeutic agents discussed above. Because it is the first non-surgical treatment to be tested extensively for safety and effectiveness in international multi-institutional clinical trials, it is supported by evidence gathered under more stringent and exacting conditions than in any other study of Peyronies Disease treatment.

Indications

Collagenase Clostridium Histolyticum (XIAFLEX®, Auxilium Pharmaceuticals Inc.) is indicated for the treatment of Peyronies Disease in men with palpable plaque and deformity of 30 degrees or greater.

Use & Treatment Protocol

CCH is given as a series of injections of 0.58 mg in 0.25cc volume, directly into the plaque or scar tissue. Usually these injections are preceded by a small amount of local anesthesia. They are administered within a schedule known as a treatment cycle, which consists of a first injection followed 24 – 72 hours later with a second injection into the same site, followed a day or two later by a physical therapy stretching session known as modeling. At the time of the first injection or at some point prior to it, an erection is induced by the injection of a vasoactive drug and the area of maximal bending identified and marked. This will become the target site for CCH injection.

Risks

All adverse effects reported in studies of this agent relate to the injection site; there were no observed systemic reactions or abnormalities in any of the laboratory tests done on subjects’ blood samples. Being a mixture of non-human (bacterial) proteins, there is a potential risk for dangerous allergic reactions, though to date none have been reported in the Peyronie’s experience. The risk of tears of the tunica albuginea (“corporal rupture” or “penile fracture”), an injury which could require surgical repair, has been quantified as < 1%. Hematoma or localized blood accumulation that could take several weeks to resolve or possibly require intervention occurred in 3 – 5%, and transient blood blisters in 5%. There is a slight risk of increased skin pigmentation or transient injection site itching. Most patients experienced transient bruising, swelling, and localized pain or tenderness.

Results

Both objective and subjective responses were evaluated in the international multi institutional studies. At the end of the 52 week phase III clinical trial, a mean angular improvement of 34% was achieved, compared to 18% in those patients receiving placebo. It should be noted that this was an active placebo group as they received the same regular stretching exercises as the patients receiving collagenase, and these exercises are thought to offer a minimal amount of angular relief. Most investigators identified some fortunate collagenase – treated individuals who experienced considerably more than 34% loss in bending.

Patients’ subjective improvement was evaluated by the PDQ, or Peyronie’s Disease Questionnaire, as well as by global response questions. Globally, 61% of collagenase treated patients responded that they were significantly improved compared to 30% of placebo treated patients. The PDQ contained 4 questions about the bother patients felt from various effects of their Peyronie’s disease, with the maximum score being 16 points. Collagenase treated patients reported a decrease in 2.8 points compared to those receiving placebo who reported a decrease of 1.8 points.

Differences between collagenase and placebo in all the objective and subjective measurements above were tested by standard methods and found to be highly statistically significant. There were other interesting findings of subgroup analysis of the clinical trial data: patients responded equally well to treatment regardless of age group, severity of bend, or presence / absence of diabetes or trauma. The other observation that warrants mention is that there was no observed relationship between degree of bending and the subjective bother score. In other words, men with bends in the 30 – 45 degree range were as bothered by their Peyronie’s Disease as men with 60 – 90 degree bends.

Before treatment photo
after treatment photo

Before and After photos of patient receiving Collagenase Clostridium Histolyticum (Xiaflex®)

Availability

European Society of Sexual Medicine Cover

Click to read article

At the time of this writing, we have treated a number of patients with Xiaflex® covered by their insurance plans. Noridian, the Medicare contractor for our west coast region, has indicated that this drug is covered by Medicare. For those patients paying cash it is available on a 48 hour basis from the distributor.

This article was written for the newsletter of the European Sexual Medicine Society, and gives a good overview of the Xiaflex – related papers presented at the 2013 American Urological Association meeting.

The Nesbit Operation & Procedure

This operation, or its various modifications, corrects bending by plicating (gathering) the convex or outer side of the bend. Counteracting the relative shortage of tunica albuginea on the concave side straightens the penis, though length is reduced slightly as a consequence. Still, this procedure is less likely to cause erectile dysfunction than tissue grafting, and remains the first choice for moderate bends without associated diameter reduction. It is the best way to surgically correct congenital curvature.

Temporalis Fascia Graft Procedure for Bent Penile Shaft Treatment

These procedures involve the replacement or expansion of scarred tunica albuginea with grafts of healthy tissue from another site. Originally, grafts were used to repair the defect that remained after excision of a Peyronie’s plaque. More recently, surgeons have been using grafts to expand the contracted scars (or plaque) without excising them. Though some calcified plaques still require removal, this non-excisional approach seems less disturbing to erectile function, and less likely to cause postoperative impotence. Despite this risk, grafting remain the most versatile reconstructive technique, particularly suited to correcting severe bending and/or diameter constriction.

Bent Penile Implant Surgery

Penile implants are biocompatible plastic cylinders, either solid or inflatable, that are surgically implanted into the corpora cavernosum to produce a functional erection. At one time they were a first choice for Peyronie’s patients who had trouble keeping an erection. Now, with all the effective medical remedies for erectile dysfunction, they are used less frequently. In men who don’t respond to these drugs however, they remain an excellent option.

Devices

Direct application of energy or mechanical force has been used to treat Peyronie’s Disease, through a variety of applications. Ultrasound administration was studied in the past as a way to break up or loosen the scarring in plaque tissue. The results were not encouraging and this modality has fallen out of favor. Radiation therapy was also used in the past to treat PD, but due to its damaging side effects and lack of efficacy it is no longer employed. External application of shock waves from equipment used to break up kidney stones (lithotripter) has been studied for its effects in improving PD. Though there have been some cases where this appeared to improve pain, its effect on curvature is questionable. One meta analysis (an inquiry where multiple different published clinical studies were combined and analyzed together) concluded that shock wave lithotripsy was ineffective in the treatment of PD.

Currently there is increasing interest in examining the potential benefits of stretching or expanding the scarring due to PD, either by the application of Vacuum devices or by the use of traction (stretching) devices. It appears that small improvement in angulation and some increase in length is achievable through daily use. For traction devices, it appears that they must be worn for at least 2 – 3 hours daily, over 4 – 6 months. Many patients find complying with this regimen difficult.