- Psychological Impact
- Diagnosis and Treatment Guidelines
- Presentation and Epidemiology
- Etiology and Pathophysiology
Demographics and mental health status of men with Peyronie’s disease: an Association of Peyronie’s Disease Advocates (APDA) study.
Christian J Nelson, Stan Hardin, Marti McKown, Laurence A Levine, John P Mulhall
Presented at the American Urological Association Annual Meeting, May 21 – 26, 2006, Atlanta, Georgia, USA
Introduction and Objective: Peyronie’s disease (PD) has been reported to be associated with reduction in quality of life and clinical experience supports these reports. APDA (Association of Peyronie’s Disease Advocates) is a nonprofit organization whose website obtains 40,000+ hits per month. The association’s vision is to be a bridge between the public and the medical community, with a view to support PD patients and contribute to the discovery of a cure. In association with the medical advisory board, members were encouraged to complete an internet-based survey to define demographics and mental health status of PD sufferers.
Methods: Members of APDA were encouraged to complete the internet-based survey present at www.peyroniesassociation.org. Data was fashioned into a database and descriptive and logistic regression analyses were conducted.
Results: 434 men completed the web-based survey. Mean age was 51.4±12.4 years. 73% were married and 88% were Caucasian. Mean partner age was 49.2±11.6 years. 40% diagnosed PD themselves prior to physician confirmation, 14% were diagnosed by a primary care physician, and 45% were diagnosed by a urologist. 74% reported the presence of a palpable plaque, 91.5% reported penile curvature. 41% had curvature <30 degrees, 42% 31-60 degrees and 16% >60 degrees. 49.5% reported penile indentation. 9% reported pain in the flaccid state, 39% when erect. 56% reported having problems with erections since the onset of PD. 63% reported they have difficulty penetrating and 15% report that penetration caused their partner pain. 12% reported that they became depressed after PD onset, and 4% reported developing an anxiety disorder after PD onset. The most common treatments reported were the use of Vitamin E (35%), Potaba (19%) and transdermal verapamil (12%). On multivariate analysis, no significant predictors of depression or anxiety were identified.
Conclusions: These data demonstrate a number of interesting findings including 40% of men self-diagnosing, more than half complaining of ED, and most significantly 12% self-reporting depression (4 times greater incidence than the general population). Additionally, more than 10% of men had used transdermal verapamil despite the absence of efficacy data.
Impact of Peyronie’s disease on sexual and psychosocial functioning: qualitative findings in patients and controls.
Rosen R, Catania J, Lue T, Althof S, Henne J, Hellstrom W, Levine L
J Sex Med. 2008;5(8):1977-1984
Introduction: There are no validated scales for assessing the psychosocial impact of Peyronie’s disease (PD), which affects approximately 5-10% of men over age 50.
Aim: To develop a psychometrically valid outcome measure for assessing psychosocial and sexual consequences of PD. To conduct a qualitative study of men with PD and age-matched controls, and design a new patient-reported outcome measure of PD.
Methods: An expert advisory panel identified relevant topics and conceptual areas to be addressed based on clinical experience and literature reviews. A conceptual model was developed to serve as a discussion guide for qualitative interviews with geographically and ethnically diverse PD subjects and controls. Interviews were conducted in a focus-group format by a trained interviewer and were recorded and transcribed for qualitative analysis according to grounded theory concepts.
Main Outcome Measure: Focus-group interviews.
Results: Focus-group interviews were conducted with 64 men (28 PD patients, 36 controls) in 13 separate focus groups over a 3-month period. Blinded analysis of the interview transcripts identified four core domains: (i) physical appearance and self-image; (ii) sexual function and performance; (iii) PD-related pain and discomfort; and (iv) social stigmatization and isolation. Based on feedback from participants and experts, a new outcome questionnaire was developed to assess core domain responses in a structured, self-report format.
Conclusions: This qualitative study helped to refine and broaden the focus of the conceptual model for further assessment. It also confirmed that PD has a major impact on sexual and psychological function in these patients.
The chronology of depression and distress in men with Peyronie’s disease.
Nelson CJ, Diblasio C, Kendirci M, Hellstrom W, Guhring P, Mulhall JP
J Sex Med. 2008;5(8):1985-1990
Introduction: For the practicing clinician, appreciating Peyronie’s disease (PD) significant negative psychological impact is apparent. Despite this, there exists not a single study using validated instruments assessing this issue.
Aim: To document the effect of PD on the psychosocial status of men.
Main Outcome Measures: The Center for Epidemiological Studies Depression scale (CES-D) for evaluation of depression and the SF-36 for quality of life assessment.
Methods: Men (N = 92; 54 +/- 11 years of age) presenting for PD evaluation completed the CES-D, Short Form-36 (SF-36), and an inventory regarding PD. Partners were not assessed.
Results: A vast majority of men (88%) had a partner with a mean partner age of 49 +/- 11 years. The median duration of PD at presentation was 12 (1-360) months. As a whole, 48% were classified as depressed on the CES-D (26% moderate, 21% severe). These subjects were then placed into groups according to the length of time since diagnosis of PD. Length-of-time groups were: 0-6 months, 6-12 months, 12-18 months, and >18 months. The percent of men scoring above the CES-D cutoff for depression remained consistently high with no significant difference across time since diagnosis groups. These results are supported by data from the Mental Health subscale (MHS) of the SF-36 (lower scores indicate lower mental heath). For the entire sample, the MHS standardized mean of 46.80 was significantly lower (P < 0.05) than the general male population standardized mean of 50. The MHS means stayed consistently low (no statistical difference) across time since diagnosis groups.
Conclusions: Using validated instruments, we have demonstrated that 48% of men with PD have clinically meaningful depression that would warrant medical evaluation. This high level of depression stayed consistent across time since diagnosis. These data suggest that most men do not psychologically adjust to their diagnosis of PD and all men with PD should be considered appropriate mental health screening.
Diagnosis and Treatment Guidelines
Summary of the recommendations on sexual dysfunctions in men.
Montorsi F, Adaikan G, Becher E, et al
J Sex Med. 2010; 7(11):3572-3588
Introduction: Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being.
Aim: To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men.
Methods: An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area.
Main Outcome Measures: New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations.
Results: Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men’s and women’s individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie’s disease; and priapism.
Conclusions: Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.
The management of Peyronie’s disease: evidence-based 2010 guidelines.
Ralph D, Gonzaez-Cadavid N, Mirone V, Perovic S, Sohn M, Usta M, Levine L
J Sex Med. 2010;7(7):2359-2374
Introduction: The field of Peyronie’s disease is evolving and there is need for a state-of-the-art information in this area.
Aim: To develop an evidence-based state-of-the-art consensus report on the management of Peyronie’s disease.
Methods: To provide state-of-the-art knowledge regarding the prevalence, etiology, medical and surgical management of Peyronie’s Disease, representing the opinion of leading experts developed in a consensus process over a 2-year period.
Main Outcome Measures: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate.
Conclusions: The real etiology of Peyronie’s disease and the mechanisms of formation of the plaque still remain obscure. Although conservative management is obtaining a progressively larger consensus among the experts, surgical correction still remains the mainstay treatment for this condition.
Presentation and Epidemiology
Predicting delay in presentation in men with Peyronie’s disease.
Mulhall JP, Alex B, Choi JM
J Sex Med. 2010;7(6):2226-2230
Introduction: Many men with Peyronie’s disease (PD) delay presentation to a urologist. The reasons for this are unclear.
Aim: To define the differences in men who present early compared to those presenting in a delayed fashion and to determine predictors of delayed presentation.
Methods: A retrospective analysis of all patients presenting for the first medical evaluation of PD. All patients underwent a standard history and physical examination and had a standardized deformity assessment. Demographic and PD parameters were recorded.
Main Outcome Measures: Statistical comparison was used to define factors that were different between early and delayed presenters and multivariable analysis was used to define predictors of presentation >12 months.
Results: 482 patients were analyzed, 61% presenting ≤12 months, 39% >12 months. Mean patient age was 52 ± 13 years and mean duration of PD was 17 ± 30 months. Mean measured curvature was 42° ± 19°. Multivariable analysis revealed that delayed presentation patients were significantly more likely to be older (odds ratio [OR] = 4.0), to be in long-term relationships (OR = 3.6), to have dorsal curvature (OR = 2.5), to have curvature <45° (OR = 3.3), to be heterosexual (OR = 2.0), and to have simple deformity (OR = 1.5).
Conclusions: One-third of men with PD presented in a delayed fashion and they tended to be older, to be in long-term relationships, to have dorsal curvature, or to have simple deformity.
Etiology and Pathophysiology
p53-Associated Parkin-like cytoplasmic protein (Parc) short-interfering RNA (siRNA) alters p53 location and biology of Peyronie’s disease fibroblasts.
Mulhall JP, Barnas J, Kobylarz K, Mueller A
BJU Int. 2010; 106(11):1706-1713
Objective: To evaluate the impact of p53-associated Parkin-like cytoplasmic protein (Parc) short-interfering RNA (siRNA) on the location of p53 as well as the biology of Peyronie’s disease (PD) plaque-derived fibroblasts after Parc knockdown.
Patients and Methods: Plaque tissue was excised from men with stable PD undergoing penile reconstructive surgery and used to produce cultured PD plaque-derived fibroblasts. Immunofluorescence (IF) and reverse transcription-polymerase chain reaction (RT-PCR) were then used to define the location of p53 and Parc before and after siRNA. Nuclear fractionation studies were used to assess the chronology of translocation of p53 from cytoplasm to nucleus on Parc knockdown. The terminal transferase dUTP Nick end labelling (TUNEL) assay was used to assess the apoptotic indices of the PD fibroblasts after Parc knockdown.
Results: IF and PCR showed high cytoplasmic levels of p53 and Parc before siRNA. On IF, there was little or no p53 present within the nucleus before Parc knockdown. After Parc siRNA, IF showed translocation of p53 to the fibroblast nucleus, while Parc levels dropped significantly, but what Parc remained was confined to the cytoplasm with none present in the nucleus. Nuclear fractionation studies using RT-PCR confirmed this translocation phenomenon and showed the chronology of the event. All p53 had moved from the cytoplasm to the nucleus within 16 h of Parc siRNA. On TUNEL assay, apoptotic indices increased dramatically after Parc siRNA.
Conclusions: These data prove that Parc is a cytoplasmic anchor for p53 in PD plaque-derived fibroblasts and may be the primary cause of the stabilization and defunctionalization of p53 in these cells. These findings support Parc as a novel target for PD pharmacotherapy, perhaps using human siRNA technologies once commercially available.
Treatment — Pharmacologic
Intralesional verapamil prevents the progression of Peyronie’s disease.
Bennett NE, Guhring P, Mulhall JP
Objectives: To define the impact of intralesional verapamil injection therapy on penile deformity in men with Peyronie’s disease.
Methods: Patients underwent a total of 6 intralesional injections of verapamil. Penile deformity was assessed at baseline and 3 months after the last intralesional injection of verapamil during penile erection after the administration of intracavernosal medication. Measurement was recorded using a goniometer at maximum penile rigidity. Endpoints included change in magnitude of curvature, stretched penile length, penetration ability, and resolution of pain.
Results: Ninety-four consecutive patients met all inclusion criteria. Mean (+/- standard deviation) patient age and duration of Peyronie’s disease at time of baseline deformity assessment were 44 +/- 18 years and 5.2 +/- 2.7 months, respectively. At baseline 86% had dorsal and 14% lateral curvature. The mean curvature and stretched flaccid length were 50 degrees +/- 28 degrees and 12.6 +/- 3.1 cm, respectively. At the follow-up evaluation, patients were 5.2 +/- 1.8 months after their last ILV injection and were 11.7 +/- 4.2 months after the onset of Peyronie’s disease. Eighteen percent of patients had improvement of curvature, 60% were unchanged, and 22% worsened. Pain resolved in 100% of patients.
Conclusions: In response to intralesional verapamil, a minority of men experienced improvement in penile deformity; however, the majority of patients had stabilization of their deformity. This information may permit clinicians to give realistic expectations to patients considering intralesional verapamil therapy.
Treatment — Devices and Other Physical Interventions
The impact of shock wave therapy at varied energy and dose levels on functional and structural changes in erectile tissue.
Müller A, Akin-Okugbade Y, Devici S, Donohue JF, Tal R, Kobylarz KA, Palese M, Mulhall JP
Eur Urol. 2008;53(3):635-642
Objective: Only minimal literature exists on consequences of shock wave therapy (SWT) on erectile function in treatment of Peyronie’s disease (PD). This study was undertaken to define SWT impact at varied energy/dose levels at different time points on functional and structural changes in erectile tissue.
Methods: In 45 rats 2000 shock waves (sw) at 2 BAR were applied to the penis weekly sorted by one, two, and three sessions (high-dose/energy level, HD-1, HD-2, HD-3). Each group was followed for 1, 7, or 28 d before measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Fifteen control animals (C1, C7, C28) underwent anesthesia alone. Another 15 animals were exposed to three SWT sessions applying 1000 sw at 1 BAR and analyzed identically (low-dose/energy level, LD-3-1, -7, -28). Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling assay was used to define the apoptotic index (AI) and Masson’s trichrome (MT) staining was prepared to evaluate smooth muscle-to-collagen ratios.
Results: ICP/MAP ratios for all C groups displayed a mean of 64%. All SWT groups demonstrated significantly reduced ICP/MAP ratios compared to their corresponding C groups (p<0.05). The LD-3 groups showed a trend toward improved ICP/MAP ratios. LD-3-28 demonstrated significant recovery compared to HD-3-28 (55+/-8% vs. 41+/-10%, p=0.004), but remained reduced compared to C28 (63+/-5%, p=0.03). No statistical differences were seen for MT staining in SWT groups compared to C (p>0.05). AIs for the LD-3 groups were significantly lower compared to the HD-3 groups (p<0.001), but all AIs were significantly increased compared to C groups (p<0.01).
Conclusions: Overall, at both energy/dose levels, SWT resulted in a time- and treatment-dependent reduction of ICP/MAP ratios, which might be mediated partly through apoptosis and collagenization of corporal smooth muscle.
Treatment — Surgery
Inflatable penile prosthesis placement in men with Peyronie’s disease and drug-resistant erectile dysfunction: A single-center study.
Levine LA, Benson J, Hoover C
J Sex Med. 2010;7(11):3775-3783
Introduction: Erectile dysfunction (ED) frequently accompanies Peyronie’s disease (PD) and changes the therapeutic approach.
Aim: To evaluate a single-center experience with inflatable penile prostheses (IPP) in men with medication refractory ED and PD.
Methods: Ninety men underwent placement of an IPP with straightening maneuvers as necessary to address their deformity and ED.
Main Outcome Measures: Preoperative assessment included International Index of Erectile Function-erectile function domain (IIEF-EF) and duplex ultrasound to confirm ED and measure erect deformity. Postoperative assessment included a modified Erectile Dysfunction Index of Treatment Satisfaction (EDITS) questionnaire, as well as office visits at 1, 6, and every 12 months thereafter.
Results: Complete chart review was performed with mean follow-up of 49 months. Mean preoperative IIEF-EF score was 11. Full rigidity was not obtained in any patient during duplex ultrasound. Mean curvature at maximum erection was 53°. There were seven mechanical failures requiring device replacement, two revision surgeries for pump or reservoir malposition, one infected device, and two corporoplasties for distal tunica erosion. Postoperative office assessment revealed a functionally straight (i.e., <20°) erect penis and a properly positioned as well as operational device in all patients. The modified EDITS questionnaire was returned by 56 (62%). Overall, 84% of patients were satisfied with their outcome, yet only 73% were satisfied with their straightness. Patient perceived postoperative curvature correction stabilized quickly and was complete by 3 months in 84% of patients. Satisfaction with ease of inflation, deflation, and concealability was 84%, 71%, and 91%, respectively. Coital activity was reported by 91% of men in this group.
Conclusion: In men with PD and ED, IPP placement allowed reliable and satisfactory coitus for the great majority of men. Mechanical failure was 7%. Men with PD undergoing IPP placement should be counseled regarding potential penile length loss and residual curvature, neither of which appeared to interfere with coitus but may reduce satisfaction.
Penile shortening after radical prostatectomy and Peyronie’s surgery.
Benson JS, Abern MR, Levine LA
Curr Urol Rep. 2009;10(6):468-474
Penile shortening following radical prostatectomy and straightening procedures for Peyronie’s disease can be a devastating and unwelcome side effect of these operations. The majority of men undergoing radical prostatectomy for prostate cancer have a measured loss of penile length, which also can occur in men with Peyronie’s disease and may be exacerbated by surgery. Recent studies have investigated the mechanisms resulting in penile shortening, and various treatments have emerged to prevent and treat postoperative penile shortening. This article reviews the recent literature on penile length loss after radical prostatectomy and following correction of penile deformity for Peyronie’s disease.
Get more from APDA