Thursday, April 19, 2012

Peyronie's Disease

Authors: Drs Tom F Lue and Alan Shindel University of California San Francisco 2008-11-12

Peyronie's Disease: Acquired Deformity of the penis A primer for men and their partners Peyronie's Disease is a common but poorly understood condition. This article is written to give men and their sexual partners information about the disease and what treatment options may be helpful in some cases.


What is Peyronie’s Disease?
Peyronie’s Disease (PD), also known as Induratio Penis Plastica or Fibroid Sclerosis of the Penis, is a poorly understood condition of the penis that is commonly associated with penile deformity.  In most cases, the deformity is only evident during erection.  In severe cases, it may be noticeable even when the penis is not hard.  Peyronie’s Disease is primarily a condition of men in their 50s and 60s, although it can affect a man at any age.  The majority of Peyronie’s cases reported in the literature have been in Caucasian men, although it has been reported in men from every ethnic group.[1]
The most common signs of PD include:
  • Penile Deformity:
    • Penile Curvature is the most common type of deformity in PD.  The penis may bend in any direction, although an upwards bend is most common. In some cases, the bend may be in more than one direction (i.e., the penis may curve up and to one side, or down and to one side).  The degree of bending may be subtle or very pronounced. 
    •  While not as common as simple curvature, awaist” or “hourglass” defect may be present where one portion of the penis is thinner than the surrounding areas. 
  •  Penile Plaque: A firm, flat nodule (plaque) may be felt within the penis and may contribute to curvature.  If penile curvature and a plaque are present, the plaque is typically on the side towards which the penis curves. This plaque is located within the tunica albuginea, a tough sheath of tissue that surrounds the spongy erectile tissue of the paired corpora cavernosa, which are responsible for rigidity of the penile shaft during penile erection.  This plaque may accumulate calcium and become very hard, almost like a bone, in some cases.
  • Penile Pain: This is usually most severe when the penis becomes erect but may be present at other times as well.  Pain is often the first sign of a problem and occurs before any noticeable bending is     present.  In most cases, pain will go away with time although plaques and deformity may persist. 
                                                                                                                                                       
                                                                                                                                                                                           From "A Practical treatise on                                                                                                                      sexual disorders of the                                                                                                                                 male & female" Taylor,  1897            
Peyronie’s Disease usually has two distinct phases.  The first phase is called the active phase and is characterized by penile pain, palpable plaque, and increasing deformity and/or curvature of the penis.  This phase typically does not last longer than 12 months and may be significantly shorter in some men.  The second phase of PD is called the chronic phase and is characterized by resolution of pain and stabilization of the curvature/deformity.  It is during the chronic phase that calcium accumulation and ED may develop.  However, for reasons that are not entirely clear, some men will see spontaneous improvement in their penile deformity during this phase without any sort of intervention.[2]
Peyronie’s Disease is not erectile dysfunction (ED).  ED is the condition where the penis does not become hard enough to permit a man to engage in satisfying sexual intercourse, whereas PD is an anatomical deformity of the penis.  Although PD and ED are distinct conditions, estimates suggest that about 35% of men who present for evaluation of PD also have ED.[3]  The number of men with ED who are found to have undiagnosed PD is much lower; this is mostly because ED is much more common than PD.[4] 
Although PD and ED are different conditions, some men with severe cases of penile deformity from PD may have erections that are not rigid past the point where the curvature or plaque is located. In some other cases of severe curvature, the bend might be so great that it is impossible for the man to penetrate his partner without severe pain for one or both partners.
It is also important to distinguish PD from a similar condition called chordee.  Chordee is a congenital (from birth) curvature of the penis that is typically detected in newborns and is caused by abnormal development of penile structures.  Chordee is not associated with penile plaques and typically does not cause pain.  Peyronie’s Disease is an acquired deformity of the penis that is only rarely found in young men.  

When was Peyronie’s Disease discovered?

One of the first authoritative descriptions of the disease in the medical literature was by the famed anatomist Fallopius in 1561.  The condition was subsequently rediscovered by Francois Gigot de la Peyronie, royal surgeon to King Louis XV of France, in 1743.[5]  While it has been rediscovered by other physician researchers subsequent to Peyronie’s description, “Peyronie’s Disease” is the favored term for this condition amongst most contemporary urologists around the world.

How common is Peyronie’s Disease?

Peyronie's Disease  was once thought to be very rare with a prevalence of less than 1%.[6]  More recent studies have suggested that Peyronie’s may be more common than was previously thought. Three percent (3%) of men in a German study reported Peyronie’s-like changes in their penises.  In this study, the incidence of PD increased with increasing age; 1.5% of men in their 30’s reported the condition compared with 6.5% of men older than age 70.[7]  In an American study, the incidence of a penile plaque detectable by an experienced physician was as high as 9%.[8]  An important autopsy study has suggested that changes in the tunica albuginea similar to what is seen in PD may be present in over 20% of men.[9]  While changes similar to what is seen in PD may occur in many men, in a large portion of these cases, the changes are so mild that they are never noticed.  Men who do not have pain or deformity do not truly have PD.
There are several theories to explain the differences in the reported incidence of PD.  It is likely that many men with PD do not come to medical attention.  Those men who do not have pain and/or are not sexually active are seldom diagnosed with the condition as they often have little need to discuss penile deformity with their health care provider.  Additionally, some men may have a very mild form of the disease that does not cause any functional consequences and may be easily missed by most providers.  Typically, only those men who have significant pain and/or a deformity that interferes with sexual activity see their health care provider about the problem. Unfortunately, some men with painful or deforming PD may not seek medical advice because of embarrassment about their condition.
The introduction of highly effective oral therapy for ED (e.g., sildenafil citrate, tadalafil, and vardenafil; known respectively by the brand names Viagra®, Cialis®, Levitra®) since 1998 has played a major role in the increased detection of PD in recent years.  Men with ED who in the past would have been unaware or unconcerned about PD have come to realize that although medication might restore their potency, penile deformity from PD may make intercourse difficult or even impossible.

What causes Peyronie’s Disease?

While physicians have a good understanding of what makes up the plaques of PD, the exact process by which these plaques develop is unclear.  Most men with PD do not recall a specific event that preceded the onset of the condition.  The current leading theory for how PD develops is that minor trauma (sometimes mild enough that the man does not sense it) from penile buckling during sex may be a key inciting event. 
 The erectile bodies (corpora cavernosa) are covered with a tough, multi-layered covering of connective tissue called the tunica albuginea.  The tunica plays an essential role in trapping blood inside the erectile bodies of the penis, the process by which penile erection occurs.  The multilayer construction of the tunica is essential to this blood trapping mechanism.   

                                              Image reproduced by Will Haun (www.willhaun.com)
If the penis buckles during sex, there may be shearing of layers within the tunica albuginea and disruption of small blood vessels.  These small vessels may leak blood into a trapped space between layers of the tunica.  Bleeding and trauma are accompanied by the release of a number of chemicals that lead to inflammation.  Transforming Growth Factor – Beta (TGF-beta) and Fibrin are two chemical messengers thought to be very important in producing inflammation.[10]  The multi-layer make-up of the tunica may therefore limit the ability of the body to drain these inflammatory mediators away from the site of injury, leading to prolonged inflammation within the tunica after injury. 
Inflammation is usually a good thing that helps to speed the process of healing.  However, when inflammation is excessive or persistent it can lead to accumulation of toxic substances, persistence of cells that are supposed to die off after normal healing has occurred, and disruption of the normal tissue rebuilding process.[11,12] This, in turn, may lead to break down of the normal supporting network of elastin (a stretchy protein that gives body tissue elastic properties) and collagen (a strong but inflexible protein that helps to hold body tissues together)  fibers, reduction in the ability of the penis to stretch, and deformity of the penis during erection.  

Studies of PD plaques have demonstrated that the primary plaque component is disorganized collagen.  These plaques also have a low content of elastin.   Elastin is very important in expansion of the penis, and it is therefore not surprising that a defect of elastin within the penis will tend to restrict expansion with erection and hence produce a variety of deformities. [13] 

Examples of the disruption of connective tissue compared to normal is displayed in the figures below:

Collagen in normal tunica: The organized fibers are arranged in sheets that can slide past each other  during penile expansion and contraction


Collagen in Peyronie's Disease: Densely packed collagen fibers; this will prevent normal collagen sliding during penile expansion and contraction 


Elastin in normal tunica: The loose network of fibers is extending in all directions; this permits stretch and contraction of penile tissue in nearly any dimension.


Elastin in Peyronie's Disease: the fibers are reduced in number and the fibers that are present are very short and abnormal.  This tissue would not stretch normally.

Animation by Dan Rivera (http://danieljrivera.com)
 
 
Why don’t all men develop PD?
  It is likely that the majority of men suffer occasional minor trauma to the penis during sexual activity.  Despite this, most men do not develop PD.  Although the reason for this is not certain, there are a number of theories.
  • Genetics: Men with certain genetic markers and/or relatives who have PD are more likely to have the condition, suggesting that genes may play a role in the development of PD.[14]  Additional evidence for a genetic component to PD includes the association of PD with a number of other fibrotic conditions such as Dupuytren’s contracture (a process in which a thick plaque-like tissue forms in the palm of the hand) and tympanosclerosis (a process of abnormal fibrosis in the eardrum).[15]
  • Age: Penile erections in older men tend to be less rigid than those found in younger men and semi-firm erections are more prone to buckling and subsequent trauma than rigid erections.  It is also likely that the strength of the tunica albuginea decreases with age, making it more susceptible to injury.
  • Lifestyle Factors:  Other conditions that may or may not be related to PD include vascular diseases such as hypertension and diabetes as well as a history of tobacco use, pelvic trauma, and some urological procedures.[16,17]  These conditions may impair normal healing processes and contribute to PD. 

I think I might have Peyronie's Disease.  What should I do?


Like any other health problem, the first step in evaluating whether or not you have a problem that might be PD is seeing your health care provider.  Many primary care providers are not familiar with PD[18] and for this reason, you will probably need to see a urologist (a specialist in men’s genitourinary health problems) to fully evaluate the condition.
A thorough history and physical examination is the first step in assessing PD.  Your urologist will want to know when you first noticed a problem, if the condition is painful, how severe the deformity is, and whether the deformity has made it difficult or impossible to maintain a satisfactory sex life.  In some cases, it might be useful to bring your sexual partner along to the appointment to provide more information on the actual problems that PD may be causing in your sexual relationship.
A general physical examination is necessary with attention to the genitals. Some specialists prefer to examine the penis in both the flaccid (soft) and erect (hard) state so that they can accurately determine the extent of deformity.  This may be accomplished by injecting a medicine that causes penile erection through a very small needle placed directly into the penis.  This type of penile injection typically causes only minor discomfort.  As an alternative to penile injection, some urologists recommend taking photos of the erect penis at home and bringing them to the doctor’s office. An ultrasound of the penis may be used to assess the plaque and penile blood flow.[19]  This information is sometimes useful in planning treatment.

How is Peyronie’s Disease treated?

For many years, most physicians recommended a “wait and see” approach to PD because 1) it was widely believed that the condition would usually resolve itself, and 2) no effective treatments were available.  PD has been demonstrated to resolve spontaneously in around 13% of cases so a “wait and see” approach is sometimes the right treatment.[20] Additionally, men with mild deformity and/or pain may not need treatment if they are able to carry on a satisfactory sexual life. 
Treatment may be beneficial for men with PD who experience: 
  • Significant pain
  • A deformity that is severe enough that satisfying sexual intercourse is difficult or impossible
  • A deformity that is getting worse
  • Concomitant ED.
A number of treatment options are available that are likely to benefit at least some men with PD.  However, no one treatment for PD has emerged as universally effective. 

What medical (non-surgical) treatments are available for PD?

Most medical treatments currently utilized for PD are scientifically sound but have not undergone randomized placebo controlled trials (RPCTs) to establish that the treatment itself is responsible for improvements in the condition.  The use of a placebo control group (that is, a group that is similar to the group that receives a medication or intervention at baseline but does not receive the actual treatment) enables researchers to more definitely state whether or not any observed changes are due to the treatment administered.  This kind of rigorous scientific evaluation is necessary for any medication to be considered a standard of care.  Very few PD medications have undergone this kind of assessment.[21] Another problem with some trials of medication for PD is usage of combinations treatments.  While this may be effective in some cases it becomes difficult to determine which of the treatments is effective when two are administered simultaneously.
 Generally speaking, medical treatments are more likely to be effective during the active phase of the disease and probably need to be given for at least several months for any real effect to be detected.  More often than not, the medications help to stabilize rather than reverse penile deformity.  In the few studies of medications in which men have experienced improvements in penile deformity the gains are usually slight. Medications may also be useful in decreasing pain in some cases.  Medications may be utilized during chronic phase of PD, although the benefit in such cases is likely to be modest.
In the attached table are listed some of the most common medical treatments for PD.  Also included is the degree of evidence to support efficacy in stabilizing (that is, preventing worsening of) deformity, efficacy at reversing deformity, the most common side effect of each, and the authors’ opinions on these various therapies.  More detailed descriptions of each medication are included below.   All medications carry a risk of additional potential side effects; these side effects do not occur in all patients and most are relatively mild, but you should always ask your provider about potential side effects before starting any kind of treatment.
Non-surgical treatments for penile deformity from PD 


Treatment

Efficacy in Stabilizing Deformity
Efficacy in Reversing Deformity
Most Common Side Effect

Author Comments
Oral Agents
Vitamin E
Slight
Poor
None/Mild
Safe but ? efficacy
Carnitine
Slight
Poor
None/Mild
Safe but ? efficacy

Colchicine

Moderate

Poor

Diarrhea
Best taken after meals to lessen GI upset

Tamoxifen™

Slight

Poor

Blood Clots
No studies have shown convincing benefit although this has been used for other fibrotic conditions

Potaba™

Moderate

Poor

GI Upset
Very difficult to take appropriately (4x daily) and significant GI side effects


Pentoxifylline
Moderate (based on author’s unpublished experience)
Mild 
(based on author’s unpublished experience)


GI Upset
We have noted regression of calcified chronic plaques in over 50 men treated with 6 months of pentoxifylline


Herbals


?


?


?
There are very few studies of these medications and government regulations on content of herbal medications are lacking
Injections

Verapamil

Moderate

Mild

Bruising
One large uncontrolled and one small RPCT have shown benefit

Interferon

Moderate

Mild
Flu-like symptoms
One large RPCT showed benefit from this treatment

Collagenase

Moderate



Moderate

Bruising
The scientific rationale for this treatment is strong but as of now data from large RPCT is lacking

Steroids

Slight

Minimal

Tissue Weakening

May weaken tissues and make subsequent surgical repair difficult
Creams


Verapamil


Slight


Poor

Skin irritation
Some researchers have questioned whether or not this medication can penetrate to the plaque when applied topically
Physical or Electrical Force
Stretching &
Vacuum Device

?

?

Pain

Studies using vacuum or other stretching devices are ongoing

Shock Waves

Slight

Poor

Pain, Bruising
Has consistently shown benefit with respect to pain but has not been shown to improve deformity


Iontophoresis


Slight


Poor


None
In studies using this method to deliver medication to the plaque, improvements were noted regardless of medication delivered.

Additional information on oral medications for Peyronie's Disease:

  •     Antioxidant drugs: 
    • Vitamin E: This is one of the oldest treatments for PD that is still in use. It has been utilized for many decades based in large part on a non-controlled study from 1949.  Although it is generally safe to take the doses of vitamin E typically prescribed for the treatment of PD, no RPCTs have shown any benefit of Vitamin E compared to placebo for the treatment of PD.[22]
    •  Carnitine: This is a relatively new drug that works as an antioxidant.  Several early studies suggested carnitine might be an efficacious treatment for PD,[23] but subsequent studies have not shown a benefit relative to placebo.[21]
  • Anti-inflammatory drugs 
    • Colchicine: Most commonly used to treat gout, this medication is an anti-inflammatory.  While it has been reported to be efficacious in several small studies, a placebo controlled trial of 78 men published in 2004 did not show any benefit to treatment with colchicine vs. placebo.[24]  One study of 45 men with early phase PD showed that men treated with the combination of colchicine and vitamin E had less penile curvature than those treated with ibuprofen at follow-up, but in the absence of a true placebo, this result must be viewed with caution.[25]
    • Tamoxifen™: This drug is a Selective Estrogen Receptor Modulator most commonly used to treat breast cancer. It is useful in decreasing levels of TGF-beta and hence there has been interest in using it to treat PD.  Unfortunately, a small placebo controlled trial of men with chronic phase PD did not show any benefits from Tamoxifen compared to placebo.[26]
  • Miscellaneous
    • Potassium para-aminobenzoate [Potaba™]: This medication works by a complex mechanism involving modulation of enzyme processes and intracellular connective proteins. An RPCT of 75 men with PD published in 2005 provided evidence that Potaba™ is effective at stabilizing deformity and plaque size in early PD.[27]  Unfortunately, this medication must be taken 4 times a day and is often associated with gastrointestinal symptoms that are sometimes severe enough to make men stop treatment.   
    • Pentoxifylline: This medication is most commonly used to treat leg pain from peripheral vascular disease.  It has been shown to decrease inflammation and subsequent fibrosis.  It has not been investigated in large scale clinical trials but appears to be effective in some cases of PD even with calcification.[28]
    • Herbal Therapies:  Numerous herbal supplements are available online and in certain stores for the treatment of PD-like conditions.  While it is entirely possible that some of these medicines may offer some benefit to the PD patient, there is little scientific data to support their use outside of a research setting at this time.  Additionally, due to the lack of federal regulation of drugs sold as herbal “supplements,” some of these “natural” remedies may be contaminated with other drugs and/or may not even contain the advertised supplements.[29]
 
Local treatment and Injection Therapy for PD
Treatment of active or chronic phase PD plaque by application or injection of a medication into the plaque itself has been a topic of great interest in recent years.  Local therapy offers the theoretical advantage of targeting therapy directly to the area of concern, which would permit higher doses and decrease the chances of systemic side effects.  A number of substances have been investigated as local treatments. 
  • Verapamil:  This medication is a calcium channel blocker (prevents the flow of calcium in and out of certain cells) that is often used to control high blood pressure.  Verapamil has been shown to inhibit the creation of new collagen and to increase the breakdown of old collagen, both of which would be of theoretical benefit in PD.  Verapamil has been used as a topical ointment applied to the penis and as an injection directly into the plaque tissue.
    • Topical Verapamil:A recent RPCT in 57 men indicated that topical verapamil had efficacy in the treatment of PD.[30]  However, another study provided evidence suggesting that topical verapamil does not penetrate to the tunica of the penis.[31]A RPCT using an electromotive device that helps drive verapamil through the skin showed no significant difference between treatment with verapamil or placebo.  Interestingly, there was significant improvement in men treated with either verapamil or placebo after electromotive device application.[32] At this time, it is unclear whether or not topical verapamil is efficacious in the treatment of PD.
    • Verapamil Injection:  Direct injection of verapamil into the plaque area bypasses the problems of skin absorption.  A small RPCT of 14 men showed improvements in verapamil-treated men as compared to placebo treated men.[33] Two additional large but uncontrolled (no placebo group) studies of verapamil injection in men with PD have shown benefits with respect to stabilization of penile deformity and sexual function.[34,35] 
  • Interferon Injection: Interferon is a chemical messenger that plays an important role in controlling the inflammatory process in the human body.  In an RPCT of 103 men with PD, interferon-treated men had significant improvements with respect to penile curvature, plaque size, and pain. [36]   This study was relatively large and benefited from a placebo arm for comparison purposes.  Interferon is expensive and causes some mild flu-like symptoms but evidence suggests that it does have some efficacy in the treatment of PD.
  • Collagenase Injection: Collagenase is an enzyme that the body produces to break-down collagen.  One RPCT in the early 1990s suggested that collagenase was of real albeit modest benefit in the treatment of PD.[37]  Interest in this drug has recently been rekindled and an upcoming RPCT will hopefully provide more data on whether this drug will have a role in the management of PD.
  • Glucocorticoids Injection:  Glucocorticoids are steroid hormones that decrease inflammation; examples include prednisone and cortisone.  A number of studies show positive results of steroid treatment in PD but none are placebo controlled.  Steroids have tissue effects that may make surgical repair (if it becomes necessary) very difficult.  For this reason, steroids are seldom recommended for the treatment of PD in the modern era.[38] 
 

Investigational Treatments for PD
Some investigators have proposed hyperthermia (increased temperature) treatments to enhance break-down of PD plaques.  One study of this treatment yielded positive results with respect to plaque size and deformity compared to verapamil injections, but in the absence of a true control group, the efficacy of this treatment is uncertain and more studies are needed.[39]
Application of shock waves to the penis as a means of breaking up the plaque was of great interest to PD specialists in the late 1990s and early 2000s.  Many studies have suggested that this treatment may help with pain from PD, but results with respect to penile deformity have generally been inconsistent.[40]  At this time, shock wave therapy must be considered experimental and should not be recommended outside of a research setting.

What about surgery for PD?

In cases where medical treatment has failed to reverse the condition and penile deformity makes satisfactory sexual intercourse difficult or impossible, surgical intervention may be required.  Most urologists who perform surgery for PD prefer to wait until the curvature has been stable and the patient has been pain free for at least 6 months; in other words, only in chronic phase Peyronie’s Disease.  The rationale for this delay is that early intervention before stabilization of disease may result in worse defects.  Although this is considered the standard of care, it is based more on expert opinion than on scientific evidence.
There are a number of surgical options for the management of PD.  The type of surgery recommended will be based in large part on the degree of curvature, the length of the penis, whether or not ED is present, and the personal preferences of the patient and his physician.  Surgeries may be broadly divided into three categories:[41] 
  • Procedures that shorten the side opposite the curvature:  This procedure may be done under a local or general anesthetic and is performed through either a circumcising incision or through an incision made on the side of the penis.
    • Penile Plication:  In plication procedures, permanent sutures are placed on the side of the penis opposite the curvature.  There are a variety of ways to place the sutures; one of the most commonly utilized techniques in the modern era is the called the 16-dot procedure.  This procedure is simple to perform, safe, and very effective at reducing or eliminating curvature in almost all cases.  It has, however, been associated with penile shortening and complaints of mild pain in up to 10% of cases.[42]
    • Nesbit procedure: In this operation, a small ellipse (lens shape) of tissue is excised from the tunica albuginea and the edges are sewn back together.  In a large series of patients, results with the Nesbit procedure were generally favorable, with 82% reporting at least satisfactory resolution of curvature.  Penile shortening of greater than 2 cm occurred in 5% of men and the majority of men had some degree of shortening.[43]
    • Yachia procedure:  Similar in some respects to the Nesbit operation, in the Yachia procedure, a longitudinal incision is made on the convex side of the penis and then is sewn closed in a transverse fashion.  This has the effect of shortening the convex side of the penis.  This operation has generally been utilized more for chordee, although good results in the treatment of PD have been reported by some urologists who use this technique for PD.[44]
  • Procedures that lengthen the side of the penis on the side of curvature:  These procedures are recommended for cases of PD with complex or severe curvatures.  In such a situation, plication procedures may lead to excessive shortening in penile length and an approach that manipulates the plaque is preferred.  There are two approaches to managing the penile plaque itself:    
    • Plaque Excision: The plaque inside the tunica albuginea is identified and excised.
    • Plaque Incision: The plaque is identified and cut so that it no longer produces curvature; however, it is not removed.
Plaque incision is favored over excision by most modern urologists. Regardless of the approach             chosen, after manipulation of the plaque, the resulting defect (hole) in the tunica albuginea must be         covered using a graft. The word graft refers to any sort of material that is transferred to an area in the     body to fill in a defect. Examples of graft materials used in PD surgery include vascular or connective     tissue taken from another part of the patient’s body (such as a segment of saphenous vein, underside of skin (dermis) or temporalis fascia), or a commercially available tissue substitute (typically a  sterilized processed portion of connective tissue derived from an animal or human donor).  
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Plaque incision (first image) and grafting (second image).  Images adapted by Will Haun (www.willhaun.com)
 
These procedures carry a lower risk of penile shortening compared to plication and similar                   techniques.[45] They are technically challenging and are therefore usually performed only by specialists in sexual health and/or reconstructive urology. These procedures are also much more disruptive to the normal anatomy of the penis and therefore carry a higher risk of post-procedure penile numbness and ED.[39]
 
  •  Placement of a penile pump or other penile prosthetic:  For men with moderate to severe ED and PD, correction of penile curvature alone may not restore the ability to resume satisfying intercourse due to an inability to attain or maintain an erection.  Given that worsening of erectile function is possible with all surgeries for PD, placement of an inflatable penile pump or malleable silicone rods inside the erectile bodies of the penis may be the best management in some men with PD and ED or whose erectile function is border-line at best.  Penile pumps are effective at restoring firmness to the penis and are typically rigid enough to correct curvature sufficiently to permit penile penetration.[39] Occasionally, some additional manipulation (modeling) is required to adequately correct the curvature of the penis during pump placement.[46]

Conclusions

Peyronie’s Disease is a poorly understood disorder that can be frustrating for both patients and health care providers. While it is not life-threatening, the damage PD can do to a man’s quality of life and his relationship with his sexual partner is considerable.  A number of treatments with varying degrees of evidence to support their use are currently available.  Importantly, our understanding of the disorder is growing every year and with new discoveries will come new improvements in care available for men living with this vexing condition.

Additional internet resources: 

  1. Association of Peyronie’s Disease Advocates: (http://www.peyroniesassociation.org/)
  2. Peyronie’s.org: (http://www.peyronies.org/)
  3. Sex Health Matters: (http://www.sexhealthmatters.org/v2/)
  4. UrologyHealth.org: (http://www.urologyhealth.org/adult/index.cfm?cat=11) 
  5. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):  (http://kidney.niddk.nih.gov/kudiseases/topics/erectile.asp)
 

Books on Peyronie’s Disease:

  1. Understanding Peyronie’s Disease by Laurence A. Levine, M.D.
  2. Peyronie’s Disease: A Guide to Clinical Management, Laurence A. Levine, editor.

[1] Shaw K, PUri K, Ruiz-Deya G, Hellstrom WJG.  Racial consideration in the evaluation of Peyronie's disease. J Urol. 2001;165:170;687A.
[2] Gholami SS, Gonzalez-Cadavid NF, Lin CS, et al. Peyronie’s disease: A review. J Urol. 2003 Apr;169:1234-41
[3] Deveci S, Palese M, Parker M, Guhring P Mulhall JP.  Erectile function profiles in men with Peyronie's disease.  J Urol. 2006 May;175(5):1807-11; discussion 1811
[4] Kadioglu A, Oktar T, Kandirali E, Kendirci M, Sanli O, Ozsoy C.  Incidentally diagnosed Peyronie's disease in men presenting with erectile dysfunction.  Int J Impot Res. 2004 Dec;16(6):540-3. 
[5] Dunsmuir WD, Kirby RS. Francois de La Peyronie (1678 –1747): the man and the disease he described. Br J Urol. 1996 Oct;78(4):613-22.
[6] Lindsay MB, Schain DM, Grambsch P, Benson RC, Beard CM, Kurkland LT. The incidence of Peyronie’s disease in Rochester, Minnesota, 1950 through 1984. J Urol. 1991 Oct;146(4):1007-9
[7] Schwarzer U, Sommer F, Klotz T, Braun M, Reifenrath B, Engelmann U.  The prevalence of Peyronie's disease: results of a large survey.  BJU Int. 2001 Nov;88(7):727-30.
[8] Mulhall JP, Creech SD, Boorjian SA, Ghaly S, Kim ED, Moty A, Davis R, Hellstrom W.  Subjective and objective analysis of the prevalence of Peyronie's disease in a population of men presenting for prostate cancer screening.  J Urol. 2004 Jun;171(6 Pt 1):2350-3.
[9] Smith BH.  Subclinical Peyronie's disease.  Am J Clin Pathol. 1969 Oct;52(4):385-90.
[10] Devine CJ, Somers KD, Ladaga LE. Peyronie’s disease: pathophysiology. Prog Clin Biol Clin Biol Res. 1991;370:355–358.
[11] Lue TF.  Peyronie’s disease: an anatomically based hypothesis and beyond.  Int J Impot Res. 2002 Oct;14(5):411-3.
[12] Gonzalez-Cadavid NF, Rajfer J. Mechanisms of disease: new insights into the cellular and molecular pathology of Peyronie’s disease. Nat Clin Pract Urol. 2005 Jun;2(6):291-7
[13] Akkus E, Carrier S, Baba K, et al. Structural alterations in tunica albuginea of the penis: impact of Peyronie’s disease, ageing, and impotence.  Br J Urol. 1997 Jan;79(1):47-53 
[14] Nyberg LM, Bias WB, Hochberg MC, Walsh PC. Identification of an inherited form of Peyronie’s disease with autosomal dominant inheritance and association with Dupuytren’s contracture and histocompatibility B7 cross-reacting antigens. J Urol. 1982;128:48–51.
[15] Ordi J, Selva A, Fonollosa V, Vilardell M, Jordana R, Tolosa C. Peyronie’s disease in systemic sclerosis. Ann Rheum Dis. 1990;49(2): 134–135.
[16] La Pera G, Pescatori ES, Calabrese M, et al. Peyronie’s disease: prevalence and association with cigarette smoking. Eur Urol. 2001 Nov;40(5):525-30
[17] Bjeckic MD, Vlajinac HD, Sipetic SB, Marinkovic JM.  Risk factors for Peyronie's disease: a case-control study.  BJU Int  2006 Mar;97(3):570-4.
[18] LaRochelle JC, Levine LA. A Survey of primary-care physicians and urologists regarding Peyronie's disease.  J Sex Med. 2007 Jul;4(4 Pt 2):1167-73
[19] Schaeffer EM, Jarow JP, Vrablic J, Jarow JP.  Duplex ultrasonography detects clinically significant anomalies of penile arterial vasculature affecting surgical approach to penile straightening.  Urology. 2006 Jan;67(1):166-9
[20] Gelbard MK, Dorey F, James K. The natural history of Peyronie’s disease. J Urol. 1990;144:1376–1380.
[21] Hellstrom WG, Bivalacqua TJ.  Peyronie’s Disease: Etiology, Medical, and Surgical Therapy.  J Androl. 2000 May-Jun;21(3):347-54.
[22] Safarinejad MR, et al. Comparison of vitamin E and propionyl-L-carnitine, separately or in combination, in patients with early chronic Peyronie's disease: a double-blind, placebo controlled, randomized study.  J Urol. 2007 Oct;178(4 Pt 1):1398-403
[23] Biagiotti G, Cavallini G. Acetyl-L-carnitine vs tamoxifen in the oral therapy of Peyronie's disease: a preliminary report. BJU Int. 2001 Jul;88(1):63-7
[24] Safarinejad MR. Therapeutic effects of colchicine in the management of Peyronie's disease: a randomized double-blind, placebo-controlled study. Int J Impot Res. 2004 Jun;16(3):238-43
[25] Prieto Castro RM, Leva-Vallejo ME, Requeiro-Lopez JC, et al.  Combined treatment with vitamin E and colchicine in the early stages of Peyronie’s disease.  BJU Int. 2003 Apr;91(6):522-4
[26] Teloken C, Rhoden EL, Grazziotin TM.  Tamoxifen versus placebo in the treatment of Peyronie’s disease. J Urol. 1999 Dec;162(5):2003-5
[27] Weidner W, Hauck EW, Schnitker J, et al. Potassium paraaminobenzoate (POTABA) in the treatment of Peyronie's disease: a prospective, placebo-controlled, randomized study.  Eur Urol. 2005 Apr;47(4):530-5
[28] Brant WO, Dean RC, Lue TF.  Treatment of Peyronie's disease with oral pentoxifylline. Nat Clin Pract Urol. 2006 Feb;3(2):111-5
[29] Basch EM, Servoss JC, Tedrow UB.  Safety assurances for dietary supplements policy issues and new research paradigms.  J Herb Pharmacother. 2005;5(1):3-15
[30] Fitch WP 3rd, Easterling WJ, Talbert RL, Bordovsky MJ, Mosier M.  Topical verapamil HCl, topical trifluoperazine, and topical magnesium sulfate for the treatment of Peyronie's disease--a placebo-controlled pilot study.  J Sex Med. 2007 Mar;4:477-84.
[31] Martin DJ, Badwan K, Parker M, Mulhall JP. Transdermal application of verapamil gel to the penile shaft fails to infiltrate the tunica albuginea. J Urol 2002 Dec;168(6):2483-5.
[32] Greenfield JM, Shah SJ, Levine LA.Verapamil versus saline in electromotive drug administration for Peyronie's disease: a double-blind, placebo controlled trial. J Urol. 2007 Mar;177(3):972-5
[33] Rehman JL, Benet A, Melman A. Use of intralesional verapamil to dissolve Peyronie's disease plaque: a long-term single-blind study. Urology. 1998 Apr;51(4):620-6
[34] Levine LA, Goldman KE, Greenfield JM.  Experience with intraplaque injection of verapamil for Peyronie’s disease.  J Urol. 2002 Aug;168(2):621-5.
[35] Bennett NE, Guhring P, Mulhall JP.  Intralesional verapamil prevents the progression of Peyronie's disease.  Urology. 2007 Jun;69(6):1181-4
[36] Hellstrom WJ, Kendirci M, Matern R, et al. Single-blind, multicenter, placebo controlled, parallel study to assess the safety and efficacy of intralesional interferon alpha-2B for minimally invasive treatment for Peyronie's disease. J Urol. 2006 Jul;176(1):394-8.
[37] Gelbard MK, James K, Riach P, et al. Collagenase versus placebo in the treatment of Peyronie's disease: a double-blind study. J Urol. 1993 Jan;149(1):56-8
[38] Russell S, Steers W, McVary K.  Systematic Evidence-Based Analysis of Plaque Injection Therapy for Peyronie’s Disease. Eur Urol. 2007 Mar;51(3):640-7
[39] Perugia G, LIberti M, Vicini P, et al. Role of hyperthermia in the treatment of Peyronie's disease: a preliminary study.  Int J Hyperthermia. 2005 Jun;21(4):367-74.
[40] Hauck EW, Mueller UO, Bschleipfer T, Schmelz HU, Diemer T, Weidner W. Extracorporeal shock wave therapy for Peyronie's disease: exploratory meta-analysis of clinical trials.  J Urol. 2004 Feb;171(2 Pt 1):740-5
[41] Hellstrom WG, Usta MF.  Surgical approaches for advanced Peyronie’s disease patients.  Int J Impot Res. 2003 Oct;15 Suppl 5:S121-4
[42] Gholami SS, Lue TF. Correction of penile curvature using the 16-dot plication technique: a review of 132 patients. J Urol 2002 May;167(5):2066-9.
[43] Ralph DJ, al-Akraa M, Pryor JP. The Nesbit operation for Peyronie's disease: 16-year experience. J Urol. 1995 Oct;154(4):1362-3.
[44] Yachia D.  Modified corporoplasty for the treatment of penile curvature.  J Urol. 1990;143:80-2
[45] El-Sakka AI, Rashwan HM, Lue TF. Venous patch graft for Peyronie's disease. Part II: outcome analysis. J Urol. 1998 Dec;160(6 Pt 1):2050-3
[46] Wilson SK, Cleves MA, Delk JR 2nd. Long-term follow up of treatment for Peyronie's disease: modeling the penis over an inflatable penile prosthesis. J Urol. 2001 Mar;165(3):825-9