Peyronie’s Disease

Journal of Sexual Medicine interview with Dr Laurence Levine regarding current approaches to Peyronie’s Disease, particularly in the Covid-19 era. Posted on the International Society of Sexual medicine Website May 1, 2020

In the current COVID-19 environment, what role does telemedicine play in the evaluation of the PD patient?
For years, I have been providing fee-for-service telephone consultations mostly for patients calling from a distance away from my office in Chicago. I believe the same process can be quite useful especially during the COVID-19 crisis where patients may be sheltered at home and yet worried about their PD.  During the interview, I would be able to get a general idea of the onset of disease symptoms, subjective estimate of deformity, their erectile function, and review the current treatment options. These interviews are useful as oftentimes these men have obtained a good deal of misinformation about Peyronie’s disease with respect to etiology and treatment options.  As we all know there is a good deal of “voodoo” on the internet and unfortunately our own literature is wrought with difficult to interpret information, albeit less voodoo.  Although these interviews can be quite useful to get an initial idea of the patient’s condition as well as provide some reassurance that treatment is available, it is clearly not enough. In my opinion, the man with PD needs a physical examination and direct evaluation of his erection.  In my practice, I routinely perform Doppler duplex ultrasound (PDDU) evaluation of all men with PD in the flaccid and erect state following vasoactive injection.  Having said that, the ability to offer a telemedicine consultation does provide the patient an opportunity to gain useful information and possibly to initiate non-surgical therapy, such as oral medications and traction therapy before they can come to the office for a full evaluation.

Could you give us a sense of the role auto-photography plays in your PD practice?
I feel it is critical to directly examine the penis for the following reasons- it allows me to assess tunical elasticity, measure stretched length, palpate the scar and to compare the erectile response to an intracavernosal drug injection during PDDU to the patient’s erection at home, as well as to objectively measure curvature and indentation deformity.  On the other hand, I find that auto-photography has limited value.  We know that the 2D representation of the erect penis in a photograph oftentimes underestimates the true deformity and will fail to provide accurate information about severity of curvature and indentation, as well as whether there is a hinge effect or buckling that occurs with application of axial forces.  We also know that the patient’s report of deformity is oftentimes either over or under-estimated.  Therefore, in my practice accurate assessment of deformity is critical and auto-photography is frequently inaccurate. Autophotography’s primary value may be to provide remote follow-up of the patient’s progress following or during treatment once the deformity has been properly assessed in the office.

What are the key components of penile length measurement in the PD patient, flaccid and erect?
The key components in the flaccid state include measurement of stretched flaccid penile length which I measure with a rigid ruler (preferably supine) from the pubis by pushing down on the skin and pubic fat pad with the penis on full stretch perpendicular to the body plane, to the beginning of the corona.  These are two fixed points which are essential to measure at the initial consultation and at subsequent visits, particularly after any intervention.  I also like to assess the elasticity of the penis, which is more of a gestalt appreciation for the lack of “give” that one feels when gently pulling the penis away from the body.  In most men with PD there will be loss of elasticity. This seems to correlate with the patient’s perception of lost erect length and provides an opportunity to discuss how the scar tissue results in the loss of elasticity and subsequent deformity.

In the erect state, the most important measurements will be assessment of curvature with a goniometer, which is infrequently a simple sharp (elbow-like) curve with a straight component from the base to the point of maximum curvature and then a straight shaft thereafter.  More commonly, there is a more crescent-like curve which can make accurate assessment of deformity difficult. It should be recognized that the accuracy obtained with a goniometer, even in the simple sharp curve, has an intra- & inter-observer error of at least 5 degrees in any direction.  This is why I do not believe that anything less than a measured 10 degree reduction of curvature is likely to be a meaningful change in deformity.  As to indentation deformity, we are now routinely evaluating this, during maximum erection, with a string and a ruler to compare the circumference at the point of most severe indentation relative to the girth at the base and distal shaft.

You question the role of PDDU in the evaluation of the PD patient, but when does abnormal erectile hemodynamics impact upon your care, medical and surgical?
The question I have with respect to the role of PDDU in patients with PD is why any physician evaluating these men would not want to perform it.  It provides a substantial amount of information including whether there is calcification present which is critical, particularly if Xiaflex is being considered. It also provides the most objective opportunity to measure curvature and indentation deformity. All of this can be obtained following intracavernosal pharmacological injection (ICI).  PDDU also allows for assessment of penile hemodynamics, which is useful to some degree, but I think provides the least amount of valuable information with respect to clinical decision making. The real question is whether the patient does or does not obtain a full erection following ICI and whether that erection is similar to or better than what they can obtain at home. The actual measurement of hemodynamics, is clearly operator, time, and environmentally dependent and the actual accuracy of the numbers obtained are questionable as one can find different flow characteristics at different locations along the shaft as well as at different time points throughout the study.  The basic question is whether the patient can obtain a full erection adequate for intromission and whether that is equal to, better, or worse than what they would obtain at home. In my opinion, hemodynamics is most useful when the patient does not obtain a full erection and this is similar to their home erection, we can then document that there is arterial and/or venous insufficiency present which may be most useful for insurance and coverage purposes.  In men who have poor quality erections at home and during PDDU, they should be considered candidates for placement of a prosthesis with straightening maneuvers so that they can resume sexual activity as soon as possible, even if they are in the acute phase. On the other hand, if they do get a strong erectile response during the PDDU, which is similar to what they attain at home and they are in the stable phase, these measurements will guide selection of the surgical approach to correct the deformity (ie plication vs grafting).  In other words, if the patient had a very strong erectile response, similar to home, and had a severe curve and/or severe indentation with hinge effect, they would be someone who might be a candidate for a grafting procedure without an IPP, whereas the man with borderline erectile response who would not accept a prosthesis, here a plication procedure would be a better choice for that individual.  Therefore, the combination of the erectile response and deformity measurements, as well as the presence of calcification, can all be useful in terms of surgical decision-making.  For the man who is not in the stable phase, identification of grade 2 or 3 calcification, in the area of maximum deformity, should rule out the use of Xiaflex.

What is your opinion on the prognosis of future RCTs being done in the PD space?
RCTs have proven to be very difficult to perform for men with PD for several reasons.  First, any single site rarely has enough patients to power such a study.  Multi-center studies are hard to control and surely not all men with PD have similar presenting deformity or underlying comorbidities, as well as a plethora of other difficult to control variables.  But, RCTs are the foundation upon which we can build evidence to support or debunk emerging therapies.  They most likely need to be multi-center in design to be able to have an adequate number to power the trial and to have the best possible controls so that we can offer our patients reasonable hope of honest treatment outcomes.  Unfortunately, but realistically, RCTs are also very expensive to conduct. Sponsoring pharmaceutical or device companies will want to know that they have an opportunity to recoup their investment in these studies. Finally, given our current failure to understand the basic pathophysiology of PD will make the likelihood of a finding a magic bullet as a reliable treatment in the near future unlikely.

Dr. Levine, please tell us a little bit about your background and your experience of treating patients with Peyronie's disease
I first became interested in Peyronie’s disease in the late 1980’s when I did my first trial of intralesional verapamil therapy which was a dose escalating trial at the University of Chicago. This subsequently was published and my practice treating men with Peyronie’s has increased since that time.

I have a dedicated research laboratory supported for the most part by funding from grateful patients which is looking to find answers to the questions of why Peyronie’s disease scarring does not resolve and trying to find novel approaches for treatment.

I see 20-30 patients with Peyronie’s disease per week and offer all forms of therapy from observation, non-surgical treatment, and all surgical options. As a result of my experience, I have written many articles on Peyronie’s disease including editing the first textbook on Peyronie’s disease and a paperback book for the lay population entitled ‘Understanding Peyronie’s Disease’ by Atticus Books.

I was the Co-chair of the International Consultation of Sexual Medicine Committee on Peyronie’s disease in 2010 and recently co-authored of the chapter on Peyronie’s disease in Campbell’s Textbook of Urology, the premier urology textbook in the world.

Roughly, how many Peyronie's patients do you treat each year?
800-1000 per year.

What is the average age of your Peyronie's patients?
The average age is 50.

How many of your patients fall approximately into each of the following groups: mild, moderate, and severe Peyronie's symptoms?
Mild: 10%
Moderate: 50%
Severe: 40%

How common do you think Peyronie's is? Do you think it is on the rise, e.g. due to lifestyle changes or environmental issues, or are men becoming more open about seeking assistance?
Peyronie’s disease has been estimated to occur in 3-9% of men and based upon my experience, it would not be surprising to have it be as high as 10% of men, with special groups such as men with diabetes or after radical prostatectomy having an even higher likelihood of developing Peyronie’s disease.

I am not sure whether Peyronie’s disease is on the rise or that it is just being better recognized. With the advent of the internet, patients who note deformity of the penis can go search the net and learn that they may have Peyronie’s disease and then seek out evaluation and treatment. I still believe many men have the problem but do not seek evaluation due to the extreme embarrassment that this disease process can cause.

How important is early diagnosis in your opinion? Can men expect better results the sooner they start treatment and why?
I have always believed that an active approach towards Peyronie’s disease makes the best sense, particularly in the early phase where there is a possibility to prevent progression of the scarring process.

Although we do not have any reliable therapy yet, non-surgical treatment has been shown in my hands to result in a lower than expected progression rate. As a result, patients may not need to proceed to surgery and can be more proactive about addressing this problem rather than a wait and see approach which has not only been recommended in the past but is currently recommended by many practicing urologists.

Can you describe the non-surgical treatments you recommend to your patients? What influences which treatments you recommend?
My non-surgical approach has been what I refer to as my “three-armed protocol.”

This includes arm #1 with oral therapy including agents which were found to have an anti-scarring effect in the animal model of Peyronie’s disease, including pentoxifylline and amino acids such as L-arginine and L-citrulline. Unfortunately, these drugs by themselves do not have much benefit. PDE5 inhibitors (Viagra, Cialis, Levitra) have also been suggested to have beneficial anti-scarring effects but there is very little evidence to demonstrate this in humans and therefore for men who have erectile dysfunction and Peyronie’s disease, I do encourage that they use PDE5 inhibitors as there may be some anti-scarring benefit as well as improving their suboptimal erections.

Arm #2 includes using intralesional injection. For the last 26 years, I have been using intralesional verapamil and have treated over 3,000 men with this approach. It is safe and I think reasonably effective. Approximately 50-60% of men will have at least a 10 degree measured reduction of curvature with an extremely low risk of serious side-effects. It is also much less costly than Xiaflex.

My general sense about Xiaflex is that this approach makes good scientific sense but unfortunately, so far, the clinical outcomes have not been particularly favorable. In my own hands, the first 50 patients that we have seen have had an average reduction of curvature of only 5 degrees which I think is unacceptably low. It may be that as we determine the characteristics of the optimum patient for Xiaflex that we will see better results. But, for a drug that is so costly and has the potential risk of serious side-effects including penile rupture, and which requires multiple visits (8) over a 6 month period I would hope to see better results.

Arm #3 is external stretch therapy. I have not really been a believer in external vacuum devices because it seems to me that the principle of stretch therapy is to induce a cellular process known as mechanotransduction. This is the cellular response to stress which induces tissue remodeling and cell growth. Therefore, placing stretch on the penis for only a 15-20 minute session with a vacuum device would unlikely provide adequate duration for the stretch to induce reliable mechanotransduction. Therefore, it has been my approach over the past 10 years to use external traction therapy which I recommend in virtually all patients as a non-surgical treatment and for those who plan to undergo surgery, to use it before surgery if possible, but certainly after surgery to encourage straight healing and prevent post-operative shortening.

Patients who present with significant pain may not be able to tolerate traction therapy but do seem to do well with intralesional verapamil as it seems to accelerate stabilization of the scarring and inflammatory process. On the other hand, patients who have extensive (grade 3) calcification, injection therapy with Xiaflex is contraindicated and will simply not work. Although physicians are beginning to experiment using intralesional verapamil for ventral curvature, this must be done with caution as there is the risk of injury to the urethra.

I also think that men who have an extended curve, rather than a discrete point of maximum curvature, do not appear to do well with intralesional Xiaflex as the drug is injected into the scar at the point of maximum curvature. If this is an extended curve or possibly there is more than one curve, these areas would not be effectively treated. In that case, intralesional verapamil may make more sense as there is a larger volume which is designed to be distributed throughout the scar tissue.

What do you consider satisfying result from non-surgical Peyronie's treatment?
The goal of non-surgical treatment should be, at a minimum, to stabilize the disease process with hopes that there would be no further progression and of course the ultimate goal would be reduction of deformity making for a more functional erection for sexual activity.

In addition, if there is bothersome pain with erection, which does tend to resolve with time, the hope is that the non-surgical treatment would accelerate stabilization of the inflammatory process responsible for the pain.

What is your view on using supplements as part of Peyronie's treatment plan?
As noted earlier I routinely use supplements such as L-arginine, L-citrulline, and even L-carnitine. There is a combination supplement that I have recommended called Stronvivo which contains all of these amino acids as well as some minerals that may help with stabilization of disease.

I use these agents because they make scientific sense based upon some elegant animal model studies done years ago but recognize that at this point, there is no evidence that oral therapies of any sort are reliable and effective treatment for Peyronie’s disease. The patient should understand this before initiating this therapy.

On the other hand, agents such as Vitamin E, Potaba, colchicine, tamoxifen, CoQ10, and other oral agents which have been used historically have never been shown in clinical trials to be beneficial and therefore, I do not recommend them.

Have you recommended using traction device or penis pump to treat penis curvature? If so, what is your experience of them? When do you recommend using each device?
As noted above, I have been a strong advocate of traction therapy as I think it makes sense.

The primary premise is to activate mechanotransduction to induce scar remodeling and possible cellular growth. The key here is duration of therapy and I think this is why we are not seeing reliable reports of efficacy with traction.

The problem is being able to wear these devices for a prolonged period of time. For years, I used a device which was maintained in place by applying a strap proximal to the corona. This oftentimes had to be secured quite tightly which made for discomfort and limited physical activity during wear time. Newer devices based upon a vacuum applied to the glans appear to allow more prolonged wear which I think has the potential to result in a more reliable response.

Let’s consider the example of braces on the teeth. These are worn 24/7 for the better part of 2 years to straighten the teeth. We know that when these devices are applied properly and the orthodontist periodically tightens them that we will have straight teeth in time. If one were to only simply grasp a tooth with their fingers and periodically twist it, it is more likely the tooth will snap off than it will actually be induced to move. Therefore, it is critical for the penis that the traction be applied for an extended period of time to induce the necessary changes which is why I am not an advocate of vacuum therapy.

It is my opinion that traction therapy can be applied during the acute phase and likely the sooner the better if the patient can tolerate it. If wearing traction exacerbates pain then I would hold off on traction until the pain resolves which may be helped with oral therapy including anti-inflammatories and possibly intralesional verapamil injection.

I do also recommend traction therapy for men who are considering surgical straightening. They can use it prior to surgery and certainly on a daily basis for three months after surgery once the wound heals adequately to facilitate comfortable wear time.

What do you recommend for men that also suffer from low erection quality / erectile dysfunction?
For those men who have deformity which does not completely interfere with sexual activity but have erectile dysfunction which makes intercourse less satisfying or impossible, PDE5 inhibitors like Viagra, Cialis, Levitra, and Stendra are recommended. These drugs also have a potential anti-scarring effect and therefore may be beneficial.

If on the other hand they do not respond adequately to a PDE5 inhibitor, then these men should be considered candidates for placement of a penile prosthesis with straightening maneuvers to address the penile deformity.

In the circumstance when the man has PD and ED which does not respond to pills, the man need not wait the 1 year or so for the disease to stabilize as during this time, there could be further loss of length and worsening of curvature. Therefore, if they have advanced erectile dysfunction, placement of a prosthesis with straightening maneuvers can be performed at any time.

Approximately how many (%) of your patients do not respond to non-surgical treatment and therefore require penis surgery? Have you been able to identify any common characteristics among those patients?
This is a difficult question as some men may have mild improvement on my “three-armed” non-surgical protocol and find that the amount of improvement they have allows them to be sexually active again without pain and without needing surgery. On the other hand, there are patients who have stabilization and/or improvement which is not satisfactory to them and therefore move forward with surgical correction.

I would say that in my practice, at least 40% of men who initiate non-surgical treatment ultimately move ahead with surgical correction. The most common characteristics of those patients will be those who have severe curvature in excess of 60 degrees and/or significant indentation causing a hinge effect. Oftentimes, men with hinge effect and severe indentation also have extensive Grade 3 calcification in that area. These men will most commonly need surgical correction with partial plaque excision and grafting if they have excellent quality erections, but if they do not, prosthesis placement is recommended.

There is some risk involved with any surgery. In your experience, how common are serious side effects after penis surgery (e.g. erectile dysfunction, penile shortening, reduced penile sensation, loss of elasticity)?
All men considering surgical treatment need to understand that there are risks including incomplete straightening and recurrent curvature which in our reported experience is around 6-10% but very rarely requires any further treatment. Change in sexual sensitivity tends to be a short-term process which resolves within weeks to months. So far in my experience, I have no patients who have a permanent loss of sensitivity which results in the inability to experience sexual pleasure or orgasm.

Loss of length is intrinsic to the Peyronie’s process. Most men should understand that they have lost elasticity in the tunical tissues as a result of the scarring process and that the goal of surgery is to make them functionally straight and not necessarily restore the penis they had before developing Peyronie’s.

Therefore, setting expectations for patients with respect to length preservation is an important part of the consent process. I always measure the penis on stretch when I first see patients and subsequent to any treatment. For the most part, men do not lose length if they are engaged in non-surgical treatment particularly if they are using traction therapy where they are more likely to gain 1-2 cm of length on stretch. In addition, some length is more likely to be recovered in those who undergo grafting especially if they use post-operative traction therapy.

The most dreaded complication for men with Peyronie’s disease is erectile dysfunction after surgery. All surgical studies show a lower rate of erectile dysfunction after plication surgery but this operation may result in a greater loss of length and certainly does not address indentation or hinge effect deformity.

On the other hand, grafting procedures require exposure of the underlying cavernosal erectile tissue which may predispose to venous leakage causing post-operative erectile dysfunction. Therefore, the patient who is considering grafting needs to be carefully counseled on the risk of post-operative ED.

In our published experience about 30% of men note some diminished rigidity but not necessarily complete erectile dysfunction. Most of these men will respond satisfactorily to a PDE5 inhibitor. Therefore, for men who are considering grafting surgery, the best candidates will be those who have excellent quality erections preoperatively. In those men who have borderline erections and refuse to have a penile prosthesis placed they must understand that they may need a prosthesis down the road.

For patients that have undergone surgery to treat their Peyronie's disease, do you recommend some post operation treatment for them? If yes, what do you recommend?
My post-operative protocol always includes a rehabilitation program. I have suggested to patients that this is much like what would be recommended by an orthopedic surgeon after a hip or knee replacement, where an intensive process of rehabilitation is recommended before full activity.

Following Peyronie’s surgery, all patients undergoing plication or grafting will begin with massage and stretch therapy 2 weeks after surgery and do this for 5 minutes twice per day for 4 weeks.

For those who undergo grafting, they will begin bedtime low-dose PDE5 therapy for 1 month beginning 1 week after surgery. They will also do the massage and stretch, and all surgical patients, once the wound can tolerate the pressures of stretch therapy will begin external traction daily for 3 or more hours for 3 months to guide straight healing and prevent post-operative shortening.

For those patients who undergo penile prosthesis placement, typically we begin cycling the device 4-6 weeks after surgery and encourage gentle modeling of the penis should there be any residual curvature once they can tolerate it.

What do you recommend that men with Peyronie's disease should do (or not do) to prevent the disease from getting worse?
My own experience has suggested that early initiation of non-surgical treatment for patients in the acute phase can reduce the likelihood of progression of disease. It has been suggested that up to 50% of men presenting during the acute phase may have progression should they do nothing at all.

On the other hand, in our own studies looking at combination therapy with oral treatment, intralesional verapamil and traction, show that only 6-10% experienced progressive deformity. Therefore, it seems that initiating some form of non-surgical treatment during the acute phase is a good idea to reduce the likelihood of getting worse.

How do you address the emotional side of Peyronie's? What can men do to deal with the distress caused by the disease?
This is a very good question as I always note to patients that Peyronie’s is both a physically and psychologically devastating disorder. For the most part, when patients first present with this problem, they almost always come with their sexual partner. Clearly, this is a couple’s problem and having the support of the partner can be quite beneficial.

I try to set their expectations appropriately in terms of what we can potentially accomplish from medical and/or surgical therapy and that the goal is to make them functionally straight and to preserve their erectile function. In spite of these discussions, many men still remain dissatisfied with the outcome of their treatment because they don’t get back the erection they used to have. This is quite understandable and if the distress is difficult for them to cope with, then we encourage counseling with a sex therapist.

In your opinion, how can partner or friend best support man with Peyronie's disease?
The partner or friend can be a supportive individual who should not diminish the importance of the affect that Peyronie’s can have on a man’s psyche.

As I like to remind my patients, Woody Allen notes that “my brain is my second favorite organ.” Clearly, any change in the penis, regardless of severity, can result in devastating consequences to the man’s self-esteem, self-image, and psyche and therefore, a supportive partner can be most beneficial. When this is not enough, I do strongly recommend the counseling of a sex therapist who is familiar with Peyronie’s disease.

What can be done to raise the awareness of Peyronie's, both among the public and health professionals?
I think that there has been a marked increase of awareness of Peyronie’s disease within the general public as a result of the advertising campaigns by the manufacturers of Xiaflex in particular. They should be congratulated for their efforts here.

In addition, websites such as this one and the Association of Peyronie’s Disease Advocates can also be useful resources for men with Peyronie’s to pursue information that is hopefully vetted and not reported to be the “next best thing” by individuals who have little or no experience with the treatment of this complicated disease process.

For physicians, educational lectures and symposia held at regional, national, and international conferences have also, I think, enhanced the awareness of Peyronie’s disease and have increased making the correct diagnosis, but many physicians see very little Peyronie’s disease and only recall the historically recommended treatments such as “observation until it stabilizes” or such things as vitamin E which are clearly not only worthless, but may allow progression of disease.

What does the future hold for Peyronie's patients? Are there any interesting new treatments on the horizon (short term and long term)? Do you think Peyronie's will ever become curable?
To my knowledge, there is nothing promising on the horizon. Research is being done in a limited number of labs, primarily because of lack of funding for this research.

The goal of research in my laboratory has not been so much as to discover why Peyronie’s occurs, but why doesn’t the scar go away. It does appear that it is due to inhibition of the last phase of wound healing known as the remodeling phase and this may be due to the inhibition of the enzymes which break down collagen. This is clearly a simplified explanation but may be the foundation for finding an effective non-surgical treatment.

Variations on the use of shockwave are being considered as well as stem-cell, platelet rich plasma, and amniotic factor injection are being examined but must be used with great care as there is no clear evidence of efficacy at this time and patients who have this problem will be at risk to spend a good deal of money on treatments which promise benefits which to me would be the equivalent of voodoo or snake oil.

Anything you would like to add?
I think the most important message to the man who develops Peyronie’s disease is to find a local expert, or travel to see an expert who can give them proper counsel, present the treatment options, and set their expectations properly as to what type of outcomes they could have. Being proactive has the potential to prevent progression and certainly may result in a diminished deformity and a more functional erect penis.

Surgical treatment remains the “gold-standard” as it is the most rapid and reliable way to correct deformity in men who have stable disease and even grafting could be an appropriate approach in the properly selected patient with severe deformity (curvature and/or hinge effect) so long as he has excellent preoperative erections.

Men with Peyronie’s should exercise caution about pursuing non-proven treatments as it will likely waste their time and money, and may result in adverse effects. Therefore, participation in clinical trials when they are available should be encouraged so that we can make scientific progress in the treatment of this devastating disorder.