Peyronie’s Disease: Help May Be on the Way
Jon L. Pryor, MD, MBA, Professor of Urology, Chief Executive officer, Medical College Physicians
The startling symptom of penile curvature, often accompanied by a penile mass and pain, are the hallmarks of Peyronie’s disease. Though originally described by Francois Gigot de la Peyronie in 1743, there has been little advancement in understanding the cause and, likewise, few evidence-based treatments for this frustrating problem. However, The Medical College of Wisconsin Department of Urology is participating in a trial for treating Peyronie’s disease, so help may be on the way.
Most men and many physicians don’t know anything about Peyronie’s disease; yet, it is a fairly common problem. Men can have Peyronie’s in their 30’s, but there is an age- related increase with an overall prevalence of around 3 percent. An autopsy study suggested Peyronie’s may have a prevalence of 22 percent, which illustrates that this disease is under-reported — most likely because of embarrassment of the patient and/or physicians not knowing much about Peyronie’s.
Despite continued research on the etiology of Peyronie’s, we still do not know the cause; we attribute it to a combination of genetic predisposition (it is associated with Dupuytren’s contractures and has a higher incidence in those with a positive family history) and minor penile trauma, most likely from intercourse. The underlying result is a fibrotic reaction, loss of elastic tissue, and formation of a scar (plaque) in the connective tissue (tunica albuginea) that covers the erectile bodies in the penis. This causes curvature and often pain, development of a palpable plaque and sometimes worsening of the quality of erections. Pain typically goes away and the curvature stops getting worse and stabilizes in approximately 12 to 18 months.
Given that we do not understand the etiology of Peyronie’s disease, it is not surprising that there is a myriad of oral “cocktails” that have been touted for its medical management. These include vitamin E, Potaba, tamoxifen, colchicines, L-arginine, carnitine, pentoxifylline, and phosphodiesterase type-5 inhibitors (e.g., Cialis, Levitra, and Viagra). Unfortunately, there are very few randomized studies in humans and virtually all of them show no clinical benefit.
Another non-surgical treatment that has been used over the past couple of decades is injecting medications into the plaque to decrease inflammation and scar formation. Initially, steroids were tried. Steroids are anti-scarring, so their use makes biologic sense, but unfortunately, this method did not work well. Injection of verapamil, which has been shown to decrease the growth of fibroblasts and extracellular matrix production, is probably the most widely used medication for intralesional plaque injection. There have been few randomized studies, but several retrospective studies show the curvature improves between 15 to 30 degrees in about half of patients. There has been one large randomized trial on intralesional plaque injection that used alpha interferon; I was one of the authors of this study, and we showed some improvement in curvature, but the improvement was minimal (9 degrees better than placebo) and alpha interferon is expensive.
For a disease that affects so many men and was initially described more than 200 years ago, the progress in treatment has not been impressive. However, The Medical College of Wisconsin Department of Urology is participating in a study involving collagenase that has potential to change how we treat Peyronie's. Collagenase clostridium histolyticum, which hydrolyzes the triple helix of collagen, has been approved by the FDA for use in decreasing the scarring in Dupuytren’s contractures. In a double blind, randomized Phase II trial involving 147 patients, collagenase clostridium histolyticum or placebo was injected into the plaques. The medication was well tolerated and resulted in greater than 25 percent improvement in penile curvature in 60 percent of patients as reported at the American Urological Association in 2009. This initial success was the impetus for a new, large placebo controlled randomized study to further evaluate the efficacy of intralesional collagenase clostridium histolyticum. We are one of the sites participating in this study. Though the study is now closed to patients, we eagerly await the results to see if there is finally a good, well-documented, evidence-based treatment for Peyronie’s. Until then, we have no access to the medication, so we continue to use verapamil as our primary medication for intralesional treatment.
Once the plaque has stabilized, which means the pain has resolved and there is no worsening of the curvature, there are surgical treatments that work well to correct the curvature. If the curvature is less than 60 degrees, we can surgically plicate the opposite side of the penis from where the plaque is located, which basically curves the penis in the opposite direction, thus straightening it. This procedure, called a Nesbit, is safe and tends to be very effective. The only drawback to a Nesbit is that it can shorten the penis around 1-2 centimeters. If the curvature is greater than sixty degrees, we incise the plaque, stretch the penis straight (which opens up a space in the plaque incision), and suture a graft into the space. The incision and grafting procedure has the advantage of minimizing any penile shortening, but can worsen erections, particularly in those who have some erectile dysfunction (ED) to begin with. In patients with significant curvature from Peyronie’s and significant ED, we typically insert an inflatable penile prosthesis, which corrects the curvature and ED.
It’s easy to see why the treatment, especially in early stages, is non-standardized and often frustrating for patients and their physicians. Our goal is to provide reassurance to the patient. It starts with the diagnosis, so that any worry about cancer or other concerns are put to rest. We provide educational material about what we do know about this disease. Though there is little evidence that oral therapy does any good, it generally does not hurt, so patients who feel that they have to try something can. If they are really bothered, we usually suggest verapamil intralesional injections, which require an injection every two weeks for a total of six injections. Most importantly, in these early stages, we encourage patience for the process to stabilize. At that point, we can work with the patient to tailor the right therapy, whether it is a plication (Nesbit), a plaque incision and patch, a prosthesis or nothing. In the meantime, we will stay on the forefront through clinical trials and hope some encouraging results will give us a better alternative to treat this problem.