Continuing Education Activity
Peyronie disease (PD) is a non-malignant disorder causing curvature of the penis and painful erections. It is a disorder of wound healing of the tunica albuginea, which results in fibrosis or scarring of the tunica albuginea. This activity reviews Peyronie disease. It describes the evaluation and management of the disease and highlights the role of the interprofessional team in ensuring the best patient outcomes.
- Review the pathophysiology of Peyronie disease.
- Describe medical options to treat Peyronie disease.
- Outline the surgical options to treat Peyronie disease.
- Summarize the role of the interprofessional team in evaluating and managing this disease to ensure the best patient outcomes.
Peyronie disease (PD) is a progressive and non-malignant disorder of the penis resulting in an abnormal curvature when erect. The condition is named for François Gigot de la Peyronie in 1749, who was a French surgeon and cofounder of Académie Royale de Chirurgie. It was first described in 1561. The abnormal curvature is caused by scar tissue in the erectile tissue; however, the exact mechanism responsible for the formation of this scar tissue remains elusive.
PD is reported to affect more than 1 in 10 men in the United States. Common to many sexual disorders, Peyronie disease can understandably cause significant distress to patients. Problems arise from the deformity and resultant impaired appearance and function, but also because PD is associated with erectile dysfunction, which is in itself a distressing condition. This chapter seeks to cover the etiology and pathophysiology, epidemiology, history and examination findings, and common evidence-based treatments.
A basic understanding of the penile anatomy is required to appreciate the etiology and pathophysiology of Peyronie disease. The penis consist of two erectile chambers called the corpora cavernosa that run along the length of the penis. During an erection, these chambers fill with blood, resulting in an increase in the size and rigidity of the penis. Each corpus cavernosum has a sheath of elastic fibers called the tunica albuginea, which is made up of predominantly type 1 collagen fibers. The two corpora cavernosa are separated by a condensation of the tunica albuginea in the midline, forming a septum that attaches to the top and bottom of the penis.
In Peyronie disease, a fibrous plaque forms in the tunica albuginea of the corpora cavernosa. This inelastic plaque changes the smooth upward curvature of the erect penis to a more kinked appearance. The exact mechanism the plaque forms is yet to be definitively established; however, many studies and theories have attempted to shed some light on the pathophysiology.
A generally accepted theory is that the plaque forms as a result of trauma to the penis. When the penis is abnormally squeezed or bent, the buckling forces result in overstretching and eventual delamination of the tunica albuginea fibers where the septum attaches. There is also damage to the microvasculature resulting in extravasation of blood, and a subsequent inflammatory cascade is triggered. The inflammatory process begins with a change of collagen from type I to type III collagen in the tunica albuginea; fibrin is deposited. Invading macrophages release elastase which breaks down the elastic fibers in the sheath of the corpora cavernosa, thus reducing the elastic properties of the tunica albuginea.
This theory explains to some extent why PD occurs following penile trauma. Unfortunately, many patients do not recall any significant trauma. Other theories have been suggested to explain the formation of the plaques including, microvasculature injury, chromosomal instability of fibroblasts involved in plaque formation, aberrations in the inducible nitric oxide pathways, and patient human leukocyte antigen (HLA) subtype. The reality is that we are unable to definitely say who will develop PD, it is more likely in susceptible men who engage in vigorous sexual or nonsexual activities (certain sports) that cause micro-injuries to the penis. Modifiable and non-modifiable risk factors of varying levels of evidence have been reported and are as follow:
Previous injury to the penis is a strong predictor of developing PD. Genital or perineal trauma, iatrogenic injury, including catheterization, cystoscopy, and TURP, are all linked to increased risks of PD. There is also some evidence to suggest that RP is associated with a 15.9% chance of developing PD, as shown in a study involving 1011 patients by Tal et al.
- Connective tissue disorders
PD is commonly associated with other fibroproliferative diseases such as Dupuytren contracture and plantar fasciitis, suggesting a significant pathophysiologic and genetic overlap between these superficial fibrosing disorders. Nugteren et al.  studied the prevalence of DD in 415 men with PD and found that 89 (22.1%) also had DD. The prevalence of DD in the general population is thought to be between 1% and 7.3%,  supporting the proposal that these conditions may have overlapping mechanisms and predisposing genetic factors. Numerous studies have linked PD to other systemic fibrotic diseases such as idiopathic pulmonary fibrosis, Paget's disease of the bone, retroperitoneal fibrosis, scleroderma, polyfibromatosis, and systemic sclerosis.
The genetic factors contributing to PD are complex, as summarised in a review by Gabrielsen. There is evidence suggesting a genetic link; however, the exact mechanism or responsible genes remain undetermined. The literature suggests that multiple genes could be involved, which confer some susceptibility of developing PD to the individual when penile trauma occurs.
Hypogonadism may increase the chances of developing PD and the severity of the disease. Moreno et al. reported a prevalence of 74.4% of PD in 121 patients with hypogonadal testosterone levels <300. Interestingly, they also found that the degree of curvature was higher in the hypogonadal group compared with men with PD and normal T levels. This was confirmed in another study involving 106 patients by Hyung et al. Androgens play an essential role in normal wound healing by modulating the matrix metalloproteinases. In deficient states, including hypogonadism, this normal healing process is disrupted, thus increases the chances of developing PD.
A study by Arafa et al. found that men who had erectile dysfunction secondary to diabetes were four to five times more likely to suffer from Peyronie disease compared to the general population. A similar higher prevalence of PD in this population has also been reported in other studies. DM is believed to accentuate the fibrotic process involved in PD.
There is some evidence to suggest that smoking is related to PD, although the correlation between the amount of smoking and risk is unclear. Similarly, the literature remains divisive with regards to alcohol, with a study by Bjekic  suggesting a strong correlation, but a larger-scale study by La Pera et al. disproving any relationship.
Men in their 60s are most commonly affected by PD , with an average age at the time of diagnosis varying from 52 - 57 years old. Although PD can still present at any age in adult life, with some reports of patients as young as 21 years old being affected.
The literature reports a prevalence of PD ranging from 0.3% to 20.3%. There is variability by country, cohort, and by age and race of patients included in the studies. Some of the variability also stems from the fact that studies may use different diagnostic criteria or data collection, such as patient or physician reporting strategies. For instance, Lindsay et al.  reported a 0.39% prevalence rate when studying a group in the USA. In contrast, Schwarzer et al. reported a 3.2% prevalence after mailing a standardized questionnaire to 8000 men in France. A much larger three-phase study by Dibenedetti et al.  investigated the prevalence of PD in 11,420 males in the US and reported rates of up to 13%. Realistically it would be difficult to accurately determine the prevalence of PD in any given population due to the embarrassment of the condition; it is likely that actual prevalence is towards the higher end of what has been reported.
As previously mentioned, the hallmark of PD is the tunical fibrosis of the corpora cavernosa resulting in plaques. The tunica is responsible for the pliancy and rigidity of the penis when it is flaccid and erect, respectively. Ultrasound and histological changes in the tunica have been described in animal and cadaveric studies. The main features include collagen deposition in unusually dense clumps with disordered, fragmented, and sparse elastin fibers. Other findings include the abnormal presence of fibrin, with one study noting a presence in 95% of PD plaques and none in control samples. Abnormal inflammation and wound healing is thought to be responsible for the increased cellularity around the tunica, which results in perivascular lymphocytic infiltrate around or within the tunica itself.
History and Physical
Although Francois Gigot de la Peyronie first described PD over 250 years ago, PD's natural history has only recently been fully appreciated. Initially based on a small cohort study in the 1970s , most patients were thought to have symptoms that would resolve spontaneously. This has since been refuted, as shown by Gelbard et al., who reported a resolution rate of only 13%, with 40% worsening with time. Similarly, Berookhim et al. noted a 12% resolution rate in untreated uniplanar PD patients; they found that younger age and time to the presentation of less than 6 months were predictors of good outcomes. In this study, 67% of patients showed no change in their disease over 12 months compared to 21% who had disease progression during this time. Another study by Kadioglu et al.  involving 307 men over eight months reported a 30% disease progression rate and a resolution rate of only 0.65%. The bottom line is that patients should be counseled that their condition is unlikely to resolve without medical treatment, and a considerable proportion of men have worsening symptoms with time.
There are two phases in PD, the acute phase and the chronic phase. In the first 6-18 months , the penile deformity progresses; there is associated pain in either the erect and/or the flaccid states. This is the acute phase, and treatment is not recommended during this period. The chronic phase is characterized by a plateau of symptoms for at least 3-6 months; the deformity remains stable with some or complete improvement in pain. The chronic phase is when treatment is most appropriate. Pain seems to be the distinguishing characteristic between the phases, as shown by Mulhall et al. They reported an improvement in pain in all 246 patients and a resolution of pain in the majority within a year of presentation; at 18 months, 89% were pain-free.
A thorough history and examination is the lynchpin of formulating a correct diagnosis in PD. This can be a delicate and distressing topic for patients as PD's ramifications on a man's sex life and relationships can profound. Consequently, clinicians should be empathetic and understanding when exploring the patient's symptoms and eliciting their ideas, concerns, and expectations of their condition. The psychosocial impact of the condition may warrant input from counselors and therapists.
A comprehensive history should include a detailed presenting complaint, past medical and surgical history. The sexual history is also particularly relevant in PD. The following are considered essential in a PD history taking:
Timing: Onset and progression of symptoms. Is the patient in the acute or chronic phase?
- Deformity: How would the patient describe the penile deformity? What is the direction and degree of curvature? Is there an hourglass deformity, hinge effect, or any other concerning abnormality?
- Erection: the degree of rigidity, ability to sustain and maintain an erection, presence of nocturnal erections.
- Pain: If pain is present, is it associated with the flaccid or erect state or both?
- Trauma: History of penile trauma/fracture, urologic procedures or surgeries
- Family history: Any family history of Peyronie’s disease or Dupuytren's disease?
- Medical/Surgical history: Diabetes, hypertension, and cardiovascular disease.
- Social history: Sexual history, smoking, and recreational drug use.
- Psychosocial factors: Impact of the condition on the patient’s mood, relationships, and self-esteem.
Accurate evaluation of penile deformity is critical for determining a baseline and planning treatment. The penis should be examined in the flaccid and erect state. This allows a better understanding of the extent of the deformity and corroboration with what the patient experiences. An objective assessment of the degree of curvature is also vital for disease monitoring and treatment progression as reliance on patient estimates is notoriously unreliable.
The penis stretch length is performed with the penis in the flaccid state. The penis is grasped at the glans and pulled gently at 90 degrees from the body. Examination in the erect state can be performed after intracavernosal injection of vasoactive substances  as per the American Urology Association guidelines. Ultrasound after intracavernosal injections is, in fact, superior to photographs or vacuum erectile device-assisted erection for accurately determining the type and degree of PD deformity (16697815). Plaque size, location, and calcification are objectively best assessed with duplex Doppler penile ultrasound. This method also assists in determining the etiology of ED if present.
PD is a clinical diagnosis; there is a limited role for diagnostic laboratory testing. However, they are valuable when a hypogonadal cause is suspected. In light of the strong correlation with other diseases, no workup would be complete without screening the patient for comorbidities such as diabetes, cardiovascular disease, and other fibroproliferative conditions such as Dupuytren's disease, plantar fasciitis, and scleroderma, amongst others.
The most important aspect of evaluation is the history and physical exam. There is no mandatory laboratory or imaging testing to complete a Peyronie disease workup.
As mentioned above, the AUA guidelines recommend performing an in-office ICI test with or without penile Doppler duplex ultrasound (PDUS) before any invasive intervention. A complete duplex ultrasound provides certain advantages, including identifying any calcifications, evaluating penile vascular flow, and evaluating the patient's erection quality after ICI. PDUS may help locate plaques not easily palpated and identify calcification in plaques. Levine et al. recently published a calcification grading system. The investigators found that patients with grade 3 or more extensive calcifications (greater than 1.5 cm in any dimension or multiple plaques greater than 1.0 cm) were more likely to undergo surgery when they also had a satisfactory erectile function. Patients with less severe calcifications of grade 1 (<0.3 cm) or grade 2 (0.3 to 1.5 cm) or no calcifications had no evidence of increased likelihood to proceed with surgery.
Thin section, high-resolution T2 MRI without fat suppression, has also been shown to be an excellent imaging modality for penile pathology, including PD. Plaques will appear as low-signal intensity areas of thickened tunica albuginea. Calcifications are poorly appreciated. Given the expense and lack of widespread availability, the utility of MRI in the routine workup for PD is unclear.
Treatment / Management
Clinicians should assess and treat a man with Peyronie disease only when he or she has the experience and diagnostic tools to evaluate, appropriately counsel, and treat the condition. Clinicians should then discuss all treatment options available and the known benefits and risks or burdens associated with each treatment. For some patients, comprehensive counseling regarding the nature of PD and the typical disease course may be sufficient to alleviate concerns. There is no agreed-upon minimum curvature necessary before the intervention. The patient's distress over symptoms and level of concern and his willingness to undergo various types of treatment should be fully considered in the decision-making process, in addition to any objective measures of curvature and erectile function.
There are a variety of oral and injectable therapies utilized in the nonsurgical management of PD. However, very few of these therapies are supported by well-designed, double-blind, placebo-controlled, randomized trials. Obstacles in having good literature to support treatment include a low number of patients enrolled in studies resulting in low power, heterogeneity of treatments and duration of follow-up, and a variety of study endpoints. During the active phase, the hallmark symptoms are pain with or without erections.
Physicians may offer non-steroidal anti-inflammatory agents to help manage pain during this period. Current AUA guidelines recommend offering oral therapy with vitamin E, tamoxifen, procarbazine, omega-3 fatty acids, or a combination of vitamin E with L-carnitine. There have been studies looking at all of these possible medications, some with encouraging results, though the vast majority are non-randomized, uncontrolled case series of various sizes. Intralesional injections are a viable non-operative option for the treatment of PD. AUA guidelines state that clinicians may offer intralesional injection with either collagenase Clostridium hystolyticum, interferon-a-2b, and verapamil. This is usually done in combination with modeling by the clinician and patient to reduce the penile curvature. It is recommended in patients with a curvature >30 degrees and less than 90 degrees and intact erectile function.
Indications for surgical treatment of PD include a deformity that impairs satisfactory sexual relations, stable deformity without pain for at least three months, extensive plaque calcification, and failed nonsurgical management. Procedure decision-making should include consideration of the nature and location of the deformity, magnitude of penile deformity, baseline erection function, penile dimensions, surgeon's experience, and patient's preference. Surgical options include penile plication, incision or excision of plaque with graft, or penile prosthesis placement. These are described briefly below:
Penile plication: the patients who are considered for this surgery should have adequate preoperative penile rigidity with or without pharmacotherapy, adequate penile length for satisfactory intercourse, simple curvature of fewer than 60 degrees, and an absence of a hinge defect or hourglass deformity. The Nesbit procedure was the first technique used for plication, and since variations of this technique have been used for correction of PD.
The surgical approach involves making a midline incision or circumcising incision and placing plicating sutures in the tunica albuginea using permanent, synthetic braided sutures contralateral to the area of maximal curvature. There are many variations on this procedure; please see the list below of all possible penile procedures. The discussion of each technique is beyond the scope of this article. Patients can resume sexual activity after 4 to 6 weeks of recovery. Potential complications of this procedure include perceived loss of penile length due to shortening of the long side of the penis, unstable penis, persistent pain, persistence or recurrence of penile curvature, penile hematoma, urethral injury, and sensation loss for neurovascular bundle injury during dorsal plication procedures. Plication procedures: Nesbit, tunica albuginea plication (TAP), Yachia procedure, Giammusso procedure, Lemberger procedure, the 16- or 24-dot procedure, Essed-Schroder tunica plication, penoscrotal plication procedure.
Plaque incision or excision and grafting: indications for this technique include full to near full pre-procedural rigidity, which might be accompanied with or without oral pharmacotherapy, complex penile deformity, simple deformity of greater than 60 degrees, large plaque, destabilizing hourglass, or hinge effect, and short penile length. For an incision procedure, an incision is made on the plaque at the point of maximal curvature on the convex side of the penis. The graft material is then placed within the defect to help lengthen the shorter side of the penis. An excision procedure involves removing part or all of the plaque and placing a graft in the defect. There are a variety of graft materials, including autologous grafts, allografts, xenografts, and synthetic grafts.
All allografts and xenografts are processed sheets of the collagen matrix. Synthetic grafts are not recommended for the management of PD. Autografts: rectus sheath, tunica vaginalis, dermal graft, buccal mucosa, fascia lata, venous patch. Allografts: pericardium, processed human pericardial grafting, fascia lata process human grafting, 4-layer 3-D printed graft. Xenografts: porcine 4-layer small intestinal submucosa (SIS), porcine 1-layer SIS, bovine pericardium, collagen sponge coated with the human coagulation factors fibrinogen and thrombin. Synthetic grafts: polyethylene terephthalate mesh reinforced silicone sheet patch graft. Complications include post-operative ED, infection requiring graft removal, penile hematoma, penile pain, recurrence of curvature.
Penile prosthesis placement. This technique is appropriate for men with ED, severe deformity refractory to medical therapy, or if profound penile instability exists. Prosthesis placement can be complicated due to the presence of plaque and corporal fibrosis. This can make dilation of the corpora difficult and increases the risk for corporal perforation. Options for prosthesis include 2 or 3 piece inflatable prosthesis or malleable prosthesis. Please see the erectile dysfunction section for further detail on prosthesis placement surgery.
Balanitis: Inflammation of the glans penis affects 11% of adult men and 3% of boys seen in urology clinics. In boys, it is caused by bacterial invasion of the soft tissue. In men, it is caused by a combination of poor genital hygiene, intertrigo, irritant dermatitis, maceration injury, and bacterial or candidal overgrowth, and treated with better hygiene practices, avoiding irritants to genitals and better glycemic controls in people with diabetes. Chordee: ventral penile curvature that occurs with or without hypospadias. Chordee is considered an arrest of normal embryological development. Typically surgical management is performed after six months of age.
Management should include intraoperative artificial erection tests at the time of repair to identify the point of maximal curvature and then to perform penile plication. Hypospadias should be corrected at the time of surgery if also present—penile fracture: trauma or contusion, fracture of the tunica albuginea during sexual intercourse. The typical story involves the sound of a "pop" with an immediate onset of severe pain and detumescence of the penis. On exam, there is typically penile swelling, ecchymosis, and possible palpable defect in the corpora cavernosa. Diagnosis can be obtained by physical exam and history and with MRI of the penis, which has excellent sensitivity for diagnosing penile fracture.
Treatment involves penile exploration with circumferential incision via subcoronal approach and closure of cavernosal injury with absorbable suture (typically 5-0 PDS). If concern for urethral injury, cystoscopy should be performed, and any urethral injury should be repaired in the same setting. Penile pain syndrome: sporadic etiology could include local conditions such as dermatitis, infection or ischemia, referred pain from the bladder, prostate, lower back or hips, neuropathic pain resulting from injury to the dorsal nerve, pudendal nerve or cauda equina, or psychiatric conditions. Persistent pain can be treated by treating the underlying disease.
Overall prognosis is good as there are numerous treatment options for the management of Peyronie disease.
Complications have been discussed in previous sections, outlying treatment options. However, plaque injection complications include penile ecchymosis, swelling, pain, corporal rupture, failure of correction of curvature. Surgical complications might consist of infection, urethral injury, penile shortening, penile pain, hematoma, loss of penile sensation, and recurrence of curvature.
Deterrence and Patient Education
Peyronie disease is a sometimes difficult problem to manage, only by the fact of the embarrassing nature of the disorder and reluctance of some patients to seek medical help. Patients should understand that this disorder is likely more prevalent than one would expect, and there are numerous options to manage it with excellent results.
Pearls and Other Issues
Peyronie disease (PD) is a disease characterized by a curvature of the penile shaft that often involves an area of plaque or fibrosis and is preceded by painful erections. PD is recognized as a wound-healing disorder of the tunica albuginea, which results in fibrosis or scarring of the tunica albuginea. The exact etiology is unknown, but many theories have been postulated. PD is likely more prevalent than previously thought and ranges from 0.5% to 20.3% within specific populations. There are numerous options for management. There are a wide variety of oral and injectable therapies utilized in the nonsurgical management of PD. However, very few of these therapies are supported by well-designed randomized trials. There are also options for injection of the plaque as well as surgical options.
Enhancing Healthcare Team Outcomes
Due to the embarrassing nature of this disorder, medical professionals need to coordinate care and communicate effectively with one another. Primary care providers (PCP) need to help identify patients who are potentially suffering from Peyronie disease. The sensitive issue requires sensitivity by the PCP. Often, males will not readily bring up this issue with their provider.
PCPs must be able to have an open and non-judgemental discussion with their patient's regarding their sexual activity and satisfaction with their sexual ability, which will often be the first checkpoint when it may be discovered that a patient has an issue such as PD. From that point on, PCPs need to understand that penile curvature or plaques are treatable problems, and the affected patients should be referred to a urologist for further management. At that point, the urologist can offer a variety of solutions to the problem, and the patient's care can take the next step forward. At the heart of the issue will be the ability to identify the patient's having the problem and get them to be seen by the proper medical professional. This will, for the most part, fall to the care of the patient's primary care provider.