The Clinical and Psychosocial Impact of Peyronie's Disease

Peyronie’s disease (PD) is characterized by the formation of palpable fibrotic tissue in the tunica albuginea of the penis. It is thought to manifest in response to recurrent microtrauma during erection in those with risk factors that may include wound-healing disorders. The initial stage of PD is thought to last from 6 to 18 months, and it is characterized by an inflammatory period with pain in approximately one-third of men. This initial phase is followed by a chronic phase when pain typically resolves and the deformity stabilizes with no additional plaque development. PD has been reported to develop in up to 9% of adult males according to published literature, but the incidence may be even higher. The most frequently affected age group is men between 50 and 59 years. Because of the associated penile deformity and effect on sexual relations, psychosocial distress is very common in those with PD. It has been reported to negatively affect self-image, sexual activity, intimacy, and mood, and it is often associated with depression and erectile dysfunction (ED). At this time, nonsurgical treatments are unreliable and have variable efficacy, and surgical treatments are reserved for those with disabling disfigurement. Moreover, surgery may result in loss of penile length and ED, and there are only a few physicians in the United States that perform such surgeries. There is a great need to increase awareness of PD in patients and general practitioners, to elucidate the pathogenesis of PD, and for the development of novel treatments for this disfiguring disease.

(Am J Manag Care. 2013;19(4 suppl):S55-S61)

Peyronie’s Disease

Peyronie’s disease (PD) is a disorder of the penis characterized by irregular, dense plaques of fibrous scars that are located in the tunica albuginea.^1,2 In the erect penis, the scars associated with PD are known to cause a variety of deformities such as curvature, shortening, narrowing, and the hinge effect (ie, buckling of the penis due to a narrowed segment in the penis shaft).^2,3 During the early phase of the disorder, about one-third of patients may experience pain caused by an inflammatory component, but pain typically resolves spontaneously within 12 to 18 months of onset in the majority of patients and deformities stabilize. Patients with PD often develop erectile dysfunction (ED).^2,4-6 Following the increasing usage of phosphodiesterase inhibitor therapy to treat ED, an increasing number of patients have been presenting to the physician’s office with PD. At this time, there remains no cure for PD and surgical treatment is only recommended to those who are sexually disabled and are willing to undertake risk.^7,8

PD is defined clinically as a wound-healing disorder that is thought to be initiated by trauma in genetically susceptible individuals.^2,9 Clinical outcomes in PD are difficult to predict. Although pain typically subsides within the first several months of onset, PD progresses in 48% of men who do not receive treatment, resulting in increased curvature and decreased penile length.⁴ Based on the unpredictable course of disease and the effects of PD on quality of life and sexual function, PD has been associated with significant psychological distress, including anxiety and depression. The psychological impact of PD may be one reason why patients delay their presentation to a physician or fail to discuss their condition with a healthcare provider.¹⁰ Moreover, the lack of knowledge about PD, among patients and physicians, may delay diagnosis.

Prevalence of PD

PD is not an uncommon disorder; the prevalence of PD has been reported to be approximately 3% to 9% in men studied.^2,11 In 1 German study of the general population, palpable penile plaques were reported in approximately 3% of men (aged 30-80 years).¹¹ Validated questionnaires were mailed to 8000 men and those who did not respond received second and third questionnaires. According to the results, 142 men (3.2% of the respondents; mean age, 57.4 years) reported having a palpable plaque. Only 1.5% of those aged 30 to 39 years reported an induration, with the prevalence of PD increasing as age increased. This study found that the most common age group of men reporting palpable plaques was greater than 70 years (Table 1).¹¹ However, other studies have reported the most common age at presentation is between 50 to 60 years (Table 2).^12,13

Results from a larger study, this time in the US general population, suggested that the rates of penile deformities or plaques were substantially higher. The US study was conducted to define the rate of PD using Internet-based technology in 16,000 randomly selected men over the age of 18 years who were asked to self-report the symptoms, diagnosis, or treatment of PD.¹⁴ Compared with results from the German study, the response rate in the US study was much higher at 71% (n = 11,420; mean age, 52.7 years); and, of those patients responding, 13.1% reported having symptoms of PD such as a penile deformity or plaque, although only 0.5% to 0.8% of respondents claimed to have been formally diagnosed with PD or to have received treatment for PD.

PD can also occur in teenagers. These patients report a high level of distress, often present to physicians earlier than adults, and have an increased number of plaques.¹⁵ Using more objective measures to identify PD, another study estimated the prevalence of PD by physical examination of the penis to detect palpable plaques or curvatures in 1440 patients with ED and found that the rate of PD was 7.9%.¹⁶ In this study, patients were significantly more likely to have PD if they had diabetes, dyslipidemia, or a psychological disorder (P <.05 for each). Similarly, a study conducted a year earlier evaluated the incidence of PD in 1133 patients with diabetes who were also screened for ED.¹⁷ The rate of PD in the diabetic population was 8.1%, and PD was significantly associated with ED (P <.001) and the duration of ED (P <.05) but not the severity of ED.

It is important to note that the prevalence rates of PD vary according to the population studied (ie, the presence of certain concomitant health conditions that may increase the probability of acquiring PD), the definition of PD, and the study design (ie, studies that use self-reported techniques to estimate the prevalence of PD may not yield results as accurate as those studies which use more objective measures of PD). It is worthwhile to note that the rates of PD from self-reported studies may be higher than published, as men with PD may be reluctant to discuss the signs and symptoms of this embarrassing disorder.

The Etiology of PD

The penis is a cylindrical organ consisting of 3 separate chambers that include 2 corpora cavernosa and a single corpus spongiosum, which is located below the corpora cavernosa (Figure 1).¹⁸ Surrounding the corpora cavernosa is a tough elastic layer of connective tissue called the tunica albuginea whose 3-dimensional structure affords flexibility, rigidity, and strength to the penis.^18-20 The chambers of the penis contain highly specialized, sponge-like erectile tissue that fills with blood during an erection, causing the corpora cavernosa to balloon and push against the tunica albuginea. The collagen and elastic fibers of the tunica albuginea are key structures that permit an increase in girth and length during erection. While the penis hardens and stretches, the skin and connective tissue of the penis remain loose and elastic to accommodate the changes. However, in men with PD, plaque formations interfere with the elasticity of the tunica albuginea and cause variable penile deformities. Changes in elastic fibers and collagen types can also contribute to the formation of penile deformities.²⁰

Although the exact etiology of PD has yet to be clarified, research suggests there are a number of factors that may predispose men to develop PD. The most widely accepted etiology is thought to involve a repetitive minor trauma to the tunica albuginea during erection with subsequent abnormal wound healing. More specifically, during penetrative sexual relations, torqueing stresses are believed to result in a delamination of the tunical fibers, causing microhemorrhage with resultant inflammation that eventually leads to scar formation in the tunica albuginea. Approximately 20% to 30% of patients may distinctly recall a particular traumatic episode.^5,21 In response to trauma, the pathogenesis of PD plaques is thought to occur via a number of potential contributors (Figure 2).²¹ These include an inappropriate fibrotic response via an overproduction of collagen and alterations in the type of collagen deposited in the tunica, an overproduction of cytokines that induce fibrosis, alterations in T-cell-mediated immunity and human leukocyte antigen system associations, or failure to degrade and clear fibrin from the tunica albuginea.^2,21,22 The exact cascade of events leading to PD remains unclear.

In addition to trauma, other risk factors that have been associated with PD include diabetes, obesity, hypertension, hyperlipidemia, smoking, and pelvic surgery (Table 3), although it remains unclear how any of these factors specifically contribute to the pathophysiology of PD.² Epidemiological studies of PD have also named certain medications (eg, thiazides and propranolol), Dupuytren’s contracture, and low androgen levels as risk factors for PD.^23-25 However, the association between medications such as thiazides or propranolol and PD is most likely simply an indication that cardiovascular disorders are more common in men with PD compared with controls.²⁴

Originally, PD was regarded as a spontaneously resolving phenomenon,²⁶ but more recent studies have indicated that only 12% of patients experience disease resolution, with 40% maintaining stable disease, and 48% developing worsening disease.^4,27 The initial phase is said to last from 6 to 18 months, with pain and inflammation occurring during this acute phase followed by a chronic phase when the penile deformity stabilizes.^5,28 Importantly, results suggest that the psychological effects associated with PD do not improve or resolve over time in the majority of patients.²⁷

Sexuality and Well-being in Patients With PD

The treatment of such a personal and embarrassing disorder as PD requires careful consideration of the psychosocial effects. Men with PD experience a variety of related psychological effects, including a reduced quality of life due to PD-related pain and discomfort, depression, low self-esteem due to physical appearance and self-image, and emotional distress. In turn, these factors have been reported to alter the quality and frequency of sexual relationships, restrict intimacy, and cause social isolation and stigmatization.

Results from a recent study in 92 men with PD suggested that men with PD should be routinely screened for long-term psychological effects including depression.²⁹ Using validated measures to identify depression in men with PD, the study found that almost half of all participants (~48%) had depression and that depression rates generally increased as the duration of PD increased; 38% of men with PD lasting less than 6 months were depressed compared with 56% of those with PD for greater than 18 months. Aside from the effects of PD on intimacy and comfort, men with PD have described the condition as a “freakish” one, which they did not know existed until diagnosis.

The rate of “emotional difficulty” may be even higher. Most recently, in a study of 245 patients with PD, 81% reported having emotional difficulty because of their condition and 54% had relationship problems. Emotional difficulty and relationship problems were determined by asking patients if PD had affected their emotional well-being or their relationship with their sexual partner.³⁰ Factors that were significantly associated with “emotional problems” included relationship problems from PD (P <.001) and loss of penile length (P = .02), whereas those associated with “relationship problems” were emotional difficulties related to PD (P <.001) and the ability to have intercourse (P = .004). These results suggested that treatments aimed at improving penile length or ED may improve psychologic outcomes.

Based upon the hypothesis that PD affects various domains of psychophysical functioning, a recent qualitative study set out to evaluate 28 men with PD and 36 age-matched controls and determine major themes and patterns of response relating to the effects of PD on 4 areas of concern: (1) sexual function and desire; (2) physical appearance and body image; (3) pain and bother (distress); and (4) interpersonal function and relationships. The study consisted of 13 focus groups conducted across 6 US cities (New York, Chicago, Los Angeles, Norfolk, San Francisco, and West Palm Beach).³¹ Men with PD were interviewed separately from men without PD in groups of 2 to 6 people, and focus groups were led by an experienced moderator who assured the participants that the information shared would be held in confidence. They stressed the need for openness and used a structured guide to lead the discussion in an open-ended format for approximately 2 to 2.5 hours.

Results from this analysis showed that the majority of interviewees with PD were concerned about 6 key areas: (1) physical appearance; (2) sexual self-image; (3) loss of sexual confidence and feelings of attractiveness; (4) sexual function and performance; (5) performance anxiety and partner’s sexual dissatisfaction; and (6) social stigmatization and isolation. Men reported a variety of penile deformities including abnormal curvature, bending, and distortion, with deformities that had mostly worsened since diagnosis.³¹ A common concern was the inability to initiate sex with a partner. Many men had lost interest in sexual activity or dating since their diagnosis because of a loss of perceived sexual attractiveness. Still, most men in the study continued to have some degree of sexual activity but complained that sex had changed after the diagnosis of PD because of problems with specific sexual positions, loss of erection, and a reduced ability to ejaculate. A mostly universal comment from respondents was the feeling of social stigmatization manifested by the difficulty in discussing PD-related issues and concerns with their partners or healthcare providers. Specific comments from respondents included, “This is a tragic deformity. Who wants to be considered less of a man?” and “It has been depressing…I’ve resigned myself to it. It’s disgusting and embarrassing.” Considering the deleterious effects on emotional well-being, patients with PD should be offered referral to a counselor early on in the disease course and should be made aware of online patient-centric resources, such as the Association of Peyronie’s Disease Advocates website (http://www.peyroniesassociation.org).³²

Identifying and Managing Patients With PD

A diagnosis of PD is typically apparent from the history and physical examination, during which the physician should try to determine onset, pain, duration, degree of deformity, and if the patient also suffers from ED.^33,34 Nonphysical symptoms such as distress or depression should also be considered and addressed during diagnosis. Of note, the physician should ask patients how the disease has impacted their life and their partner; they should also assess treatment expectations.⁷ Penile plaques are generally palpable and are mostly located on the dorsal side of the penis in two-thirds of men affected.³⁵ The consistency of the plaque (ie, soft, tender, firm, likely calcified) should be noted, as it will help guide therapy; however, plaque measurement is inaccurate using any modality and so it is not a reliable assessment to guide treatment.^2,33 The stage of disease can be predicted by the presence of pain, which is typically only manifested during erection and is more common during the inflammatory/acute stage of disease. Deformities are most apparent during erection, so the use of home photographs or an intracavernosal injection with a vasoactive agent can be helpful to determine the severity of any abnormalities; the latter modality has been described as the most accurate approach. It is important to recognize that the severity of the curvature does not predict the degree of patient distress. Patients with lesser degrees of curvature may be just as bothered as those with more advanced curvature deformity.³¹ A dynamic duplex Doppler ultrasound is not necessary but can be used to assess plaque calcification, objectively measure deformity, and measure vascular flow.³³ Unfortunately, because PD is not well understood, patients are often misdiagnosed (eg, with ED), and time from initial presentation to diagnosis and treatment can be lengthy.

At this time, there are no US Food and Drug Administration—approved treatment options for patients with PD. During the acute phase, treatment is nonsurgical and mostly consists of oral and injectable medications used off label with the goal of reducing the acute phase of disease to reduce plaque formation in the hopes of minimizing disease progression.^28,36 Nonsurgical therapies include oral/systemic therapy (vitamin E, potassium aminobenzoate, colchicine, tamoxifen, acetyl-L-carnitine), intralesional injection therapy (verapamil, collagenase, interferons), extracorporeal shockwave therapy, and penile traction devices.^7,28 Unfortunately, the available evidence shows that oral therapies are generally not effective for reducing penile deformities, although the standard of care still involves the use of such therapies.³⁶

Surgical therapy is typically reserved for patients whose plaques have stabilized, are having difficulty with intercourse, and have a curvature greater than 30°, and may include those with intractable ED.^7,8,28 Surgical techniques include penile plication (shortening the side of the penis opposite to the curvature to straighten out the penis), incision and grafting, and implanting prostheses.^3,28 Prior to any surgical procedure, penile length must be measured so that the patient understands that loss of length is most likely due to the disease process and not the surgery.³³

Unmet Needs in PD

The advancement of PD treatment and diagnosis relies on acquiring a better understanding of the multiple unmet needs facing this patient group. To begin, improvement in physician education on the subject of PD may improve outcomes since many physicians have incorrect assumptions about PD. LaRochelle and colleagues reported that many patients receive outdated or incorrect information regarding PD from their physician. Because of this, these investigators surveyed primary care physicians (PCPs) and urologists who were most likely to encounter patients with ED to determine their understanding and experience with PD.³⁷ More than 500 surveys containing multiple choice and true/false questions regarding PD were mailed out to PCPs and urologists in Illinois and Wisconsin. The surveys were designed to assess physician experience treating PD, their understanding of the disorder, awareness regarding treatment modalities, and their opinions regarding the seriousness of PD and the need for treatment.

Results of the survey showed that nearly all physicians believe PD is a psychologically distressing disorder. However, the survey showed that physicians believe the rate of PD is less than 1% (based on previous reports that PD is a rare disorder). The survey also noted that 44% of PCPs and 17% of urologists do not examine the penis during a routine physical examination, which can be useful in detecting penile plaques and can offer the patient an opportunity to discuss any concerns regarding his sexual health.³⁷

Of note, many physicians still believed that PD is mostly a self-limiting or spontaneously resolving disease, which may result in unrealistic expectations from patients with regard to prognosis. Furthermore, despite a lack of data supporting its use, the most common treatment prescribed was vitamin E in patients whose deformities were not severe enough to recommend surgery. It was assumed that vitamin E was a popular treatment choice because it is most likely believed to confer no harm.³⁷

Because the field of medicine is constantly growing, a substantial amount of new information must be communicated regularly to healthcare providers to ensure that clinicians remain aware of the newest practice changes and updates. To this end, a recent study was designed to evaluate the effects of a sustained educational program among members of the Consortium for Improvement in Erectile Function (CIEF) compared with nonmembers.³⁸ The goals of this study were to evaluate the impact of continuing medical education (CME) on attitudes and knowledge of study participants and to compare outcomes between urologists and PCPs. Results from the study showed that knowledge increased as the number of CIEF CME activities taken increased and that the knowledge base of PCPs who took more CIEF CMEs than their counterparts was almost equal to that of the urologists. A trend was also observed suggesting that ED education positively affects the physician attitude toward having ED-related discussions with their patients. Overall, long-term CME efforts had a positive effect on the knowledge and practice patterns of doctors that hopefully will be translated to enhanced clinical outcomes in the patient setting.

Conclusion

The pathophysiology of PD remains poorly understood, but it is thought to relate to the interplay of microtrauma and wound-healing disruptions. Because of the pain, disfigurement, and ED that is often associated with PD, men with this disorder frequently have distress and depression or experience greater emotional difficulties compared with men without PD. PD is not a cosmetic defect, but rather a tunical deformity which can significantly impact patients, resulting in loss of psychosexual well-being and normal sexual function. Importantly, the severity of a patient’s curvature deformity may not predict the extent of their distress. Because of knowledge deficits among the medical profession regarding PD, increased medical education is needed to increase awareness regarding the prevalence and psychological effects of PD, facilitate its diagnosis, and encourage more open communication between healthcare providers and patients. At this time, there is a lack of effective pharmacologic therapy to treat men who suffer from PD. Surgical intervention is not ideal, and only a small percentage of US surgeons perform PD surgery, presenting another barrier to PD management. A team-based approach that includes psychosocial assessment and appropriate referrals may improve outcomes. It is hoped that as the mechanisms of PD become more completely elucidated, novel treatments will become available to more effectively treat patients who suffer from PD.Author affiliation: Professor of Urology, RUSH University Medical Center, Chicago, IL.

Funding source: This supplement was supported by Auxilium Pharmaceuticals, Inc.

Author disclosure: Dr Levine reports serving as a consultant/advisory board member for Actient Pharmaceuticals, Auxilium Pharmaceuticals, Inc, and Coloplast. He also reports receipt of honoraria and lecture fees from Auxilium Pharmaceuticals, Inc, and Coloplast.

Authorship information: Concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.

Address correspondence to: Laurence A. Levine, MD, FACS, 1725 W Harrison St, Ste 352, Chicago, IL 60612. E-mail: drlevine@hotmail.com.

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