Pathophysiology Of Peyronie's Disease Research Articles

Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets.

Penile induration disease, commonly known as Peyronie's disease (PD), is a connective tissue disorder that affects the penis, leading to the development of fibrous plaques, penile curvature, and erectile dysfunction. PD is a common male reproductive system disease with a complex etiology involving multiple genes, signaling pathways, and different phenotypes. The etiology and pathogenesis of PD remain poorly understood, hindering the development of effective treatment strategies. By understanding the underlying mechanisms of PD, we can pave the way for targeted therapies and improved patient outcomes. We reviewed the epidemiology and pathophysiology of PD. We performed database searches on Google Scholar, PubMed, Medline, and Web of Science from inception to September 2023. The literature reviewed included priapism guidelines, review articles, current trial studies, and various literature related to PD. This article provides a comprehensive overview of the current research progress on the disease, focusing on its genetic factors, signaling pathways, cellular mechanisms, phenotypic manifestations, and therapeutic targets. It can help identify individuals at higher risk, aid in early detection and intervention, and provide insights into fibrosis and tissue remodeling. It can also reveal potential therapeutic targets, guide accurate diagnoses and treatment strategies, and address the impact of the disease on patients' quality of life. By integrating insights from genomics, molecular pathways, clinical phenotypes, and therapeutic potentials, our research aims to achieve a deeper and more comprehensive understanding of PD, propelling the field toward innovative strategies that enhance the lives of those affected by PD. The complex manifestations and pathogenesis of PD necessitate the use of multiple treatment methods for personalized care.

(165) Role of Penile Veno-occlusive Dysfunction in Peyronie’s Disease Patients with Erectile Dysfunction

Abstract Introduction The incidence of Peyronie's disease (PD) is 4% in the U.S. male population. Many PD patients also suffer from erectile dysfunction (ED). The etiology of ED incidence in PD men is not known, although veno-occlusive dysfunction (VOD) is often suggested. It is important to appreciate the influence of VOD in PD patients with ED, especially in regard to successful PD treatment. Objective The main objective of this study is to assess the penile hemodynamic response to intracavernous injection (ICI) of a vasoactive agent in order to evaluate the incidence of VOD in PD patients with or without ED. Methods A total of 333 men, diagnosed either with PD (n=202) or ED (n=68) or both PD and ED (n=63), visiting our Andrology clinic were included in this study. Initial ED was determined by using the International Index of Erectile Function (IIEF) score, whereas patients with penile curvature ≥30° were categorized as having PD. Penile color duplex Doppler ultrasound (CDDU) data was retrospectively collected from these patients, and parameters such as peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were used for analysis. RI (=PSV-EDV/PSV) was calculated, and VOD was confirmed when PSV ≥30 cm/sec, EDV ≥6 cm/sec, and RI <0.8 based on previously published guidelines for standardization of penile CDDU parameters. Statistical analysis was performed using MedCalc statistical software version 20.019 (MedCalc Software bv, Ostend, Belgium). Results Table 1 summarizes the CDDU results of all 333 patients. Age of the study subjects was 55.6 ± 11.3 years, with no difference between groups. Incidence of penile VOD was higher in patients with ED without PD (58.8%) or with PD (52.4%) compared to PD alone (44.6%). RI values of PD patients without ED were higher (>0.8) compared to PD patients with ED having VOD (<0.7) (P<0.001). Conclusions The current study results indicate that lower RI values suggest a higher incidence of VOD in PD patients. VOD plays an important role in the onset of ED in men with PD. Furthermore, this demonstrates the importance of performing CDDU and diagnosing the presence of VOD in further understanding the pathophysiology of PD. Disclosure No

The Etiology of Peyronie's Disease: Pathogenesis and Genetic Contributions.

Peyronie's disease (PD) is a chronic fibrosing condition that contributes to penile deformity, curvature, and pain. Initial familial studies demonstrated potential genetic links to PD. Since that time, very few investigations have significantly advanced the science in this area. Hence, there is a large opportunity and significant need to better study the underlying genomics and pathogenesis of PD. To summarize the current genomic literature relevant to PD. A review was performed of all PubMed-indexed literature from 1970-2018 relating to the pathophysiology and genetics of PD. Key findings were categorically summarized to include epidemiology, risk factors, inheritance patterns, chromosomal instability, genetic associations, epigenetics, differential gene expression, and preclinical models of PD. Summary of the current literature on the genetics of PD. PD is a common condition and has several known risk factors and comorbid disease associations. Although men with PD are believed to be genetically predisposed, there are likely several subtypes of the condition, each with varied pathophysiological disorders and contributing factors. Available data suggest that PD is associated with underlying genetic instability, including dysregulation of genes relating to fibrosis and cellular degradation, thus, resulting in abnormal plaque development and penile deformity. Preclinical models, including cell cultures and rat models, demonstrate several consistencies with PD clinical and histopathologic characteristics; however, an ideal model with spontaneous development of PD is lacking. Based on limited data, PD likely represents a heterogeneous condition, with both heritable and environmentally-driven epigenetic factors contributing to its development and progression. However, there remains a significant gap in the literature on the underlying cause and pathophysiology of the condition, suggesting a substantial need for further investigation and study. Sharma KL, Alom M, Trost L. The Etiology of Peyronie's Disease: Pathogenesis and Genetic Contributions. Sex Med Rev 2020;8:314-323.

P-01-017 ED and peyronie disease, commonly seen in diabetic patients

58 y/o male presents with progressive penile deviation and painful erection for the past eight months as well as decreased penile rigidity and difficulty with intercourse. Patient states normal desire with frequency of having one to two intercourse every week. He denies any abnormal ejaculatory functions with IELT around 5 minutes. On Psychosocial history he confesses having good relationship with a 52 y/o partner whom they have been married and lived together for over 20 years. He denies any past insulting factors. On past medical history he states having diabetes mellitus for the past 6 years which he has been watching his diet and taking Metformin and Glibenclamide. He denies any peripheral neuropathy. He denies any coronary artery diseases, hypertension, nor thyroid diseases. He has been smoking tobacco x 10yr (quit 20 years ago). no alcohol on Exam, testicles were normal size and shape. Penis was in normal size. We found a 2 x 0.5 cm Peyronie plaque to mid penis. Routine labs ordered. All came back normal except for elevated FBS and HbA1c and slightly elevated lipid. Patient was educated regarding pathophysiology of Peyronie Disease and possible treatment options. Lekoptin injection advised every other week as well as oral treatment of tadalafil 5 mg daily and Co-Q 10 100mg daily. Patient received 6 injections in 3-month period and reported significant improvement in his deviation and rigidity. Another course of 3-month injection advised to patient, however, patient declined further injection.

Understanding the cellular basis and pathophysiology of Peyronie's disease to optimize treatment for erectile dysfunction.

Erectile dysfunction (ED) is a common condition that significantly impacts a man’s physical and psychological well-being. ED is often associated with Peyronie’s disease (PD), which is an abnormal curvature of the penis. Delayed treatment of or surgical invention for PD often results in ED and therefore unsatisfied patients. The pathophysiology of PD is incompletely understood, but has been studied extensively and based on our current understanding of PD physiology, many medical treatment options have been proposed. In this paper, we will review what is known about the pathophysiology of PD and the medical treatment options that have been trialed as a result. More investigations in regards to the basic science of PD need to be carried out in order to elucidate the exact mechanisms of the fibrosis, and propose new, more successful treatment options which should be implemented prior to the onset of ED.

La maladie de Lapeyronie

Lapeyronie's disease is a common condition affecting 3.4 to 9% of the male population. Knowledge of pathophysiology, natural history, and treatment outcomes can guide the care of patients. A literature review was carried out between 1940 and 2012 in Pubmed using the keywords: Lapeyronie's disease, Peyronie's disease (PD), pathophysiology of PD, surgical treatment for PD, medical treatment for PD. Seventy-five articles were selected, including original articles, reviews, and recommendations in English or French. Few studies available are of level 1 and most of them are of 2b and 3 level of evidence. The pathophysiology of Lapeyronie's disease is controversial. Medical treatments are ineffective. Surgery should be proposed when the curvature is stabilized, and the treatment of the concavity or convexity depends on the size of the erect penis, its curvature angle and erectile function. Penile implant must be proposed to patients when erectile dysfunction is combined with severe curvature.

Peyronie's disease: contemporary review of non-surgical treatment.

BackgroundPeyronie’s disease (PD) remains a therapeutic dilemma for the treating physician. This is in spite of a large array of treatments which have been used since the time of de la Peyronie in the mid 18th century. Part of this problem is due to an incomplete understanding of the etiopathophysiology of this scarring disorder. Having a better understanding of the how and why the scarring occurs may help prevent progression, but ultimately reversing the existing scar remains the real challenge.MethodsThis review discusses the current non-surgical treatment options for Peyronie’s disease. Published articles in peer-reviewed journals are used, recognizing that the majority of the published trials are compromised by being single-center studies without a placebo control.ResultsA variety of treatments options have emerged, most with limited and unreliable benefit, but a few treatments have shown a consistent albeit incomplete response rate. Could this suggest that all PD is not the same and that the heterogeneous nature of this scarring disorder may account for why some patients respond and others do not? Further investigation of this diverse response rate may yield insights into the pathophysiology of PD. In the meantime, there have been many oral treatments offered for PD. Currently the only scientifically sensible treatments appear to be pentoxifylline, L-arginine, and possibly the phosphodiesterase type-5 inhibitors. Intralesional injection has been used for many years. The current treatment options include verapamil and interferon, with reported benefit with respect to reduced deformity and improved sexual function. Intralesional clostridial collagenase is in the midst of phase 3 trial analysis by the FDA in the USA and may become the newest and only FDA approved treatment for Peyronie’s disease. External mechanical traction therapy has also recently emerged as a technique to reduce curvature, recover lost length, enhance girth, and possibly obviate surgery.ConclusionsIt appears at this time that there is no clear, reliable and effective non-surgical treatment for Peyronie’s disease, but it does appear from the published literature that several of the available treatments can result in reduction of deformity, improved sexual function, and may at a minimum stabilize the disease process so that deformity does not get worse particularly during the acute phase of this scarring disorder. Combination therapy in an effort to create a synergy between the chemical effects of oral and injectable drugs with the mechanical effects of external traction therapy may provide the best opportunity today for reduction of deformity in the man with Peyronie’s disease.

Current and emerging treatment options for Peyronie's disease

Peyronie’s disease (PD) is a condition of the penis, characterized by the presence of localized fibrotic plaque in the tunica albuginea. PD is not an uncommon disorder, with recent epidemiologic studies documenting a prevalence of 3–9% of adult men affected. The actual prevalence of PD may be even higher. It is often associated with penile pain, anatomical deformities in the erect penis, and difficulty with intromission. As the definitive pathophysiology of PD has not been completely elucidated, further basic research is required to make progress in the understanding of this enigmatic condition. Similarly, research on effective therapies is limited. Currently, nonsurgical treatments are used for those men who are in the acute stage of PD, whereas surgical options are reserved for men with established PD who cannot successfully penetrate. Intralesional treatments are growing in clinical popularity as a minimally invasive approach in the initial treatment of PD. A surgical approach should be considered when men with PD do not respond to conservative, medical, or minimally invasive therapies for approximately 1 year and cannot have satisfactory sexual intercourse. As scientific breakthroughs in the understanding of the mechanisms of this disease process evolve, novel treatments for the many men suffering with PD are anticipated.

The Prevalence of Peyronie's Disease in Japan: A Study in Men Undergoing Maintenance Hemodialysis and Routine Health Checks

The incidence of Peyronie's disease (PD) in the general population is believed to be as high as 20%. However, most of the data concerning the prevalence of PD have been obtained from Caucasian populations. The aim of this study was to examine the prevalence of PD in Asia and among men undergoing hemodialysis and discuss the pathophysiology of PD. A total of 1,090 men who received a routine health check at our hospital (control group) as well as 130 male patients undergoing maintenance hemodialysis were enrolled. The diagnosis of PD was based on a palpable penile plaque. Hemodialysis patients were asked about their sexual activity and completed the International Index of Erectile Function-5 questionnaires. The differences between patients' and hemodialysis-associated factors, comorbidities, and medications were statistically assessed for patients with and without PD. The prevalence of PD was significantly increased among hemodialysis patients (12 patients: 9.2%) relative the control group (six men: 0.6%) (P<0.0001, odds ratio: 18.4). In both groups, the plaques were primarily allocated dorsally. In the hemodialysis patients with PD, the frequency of masturbation (P<0.05) and the incidence of moderate or severe erectile dysfunction (P<0.01) were significantly higher than those among hemodialysis patients without PD. In comparison with patients without PD, the number of acetate dialysate users was significantly higher among patients with PD (P<0.05), and none of the PD patients used angiotensin-related antihypertensive drugs (P<0.05). The prevalence of PD in healthy Japanese men is low (0.6%), which suggests the existence of racial differences in the prevalence of PD. Moreover, these results indicate that hemodialysis increases the incidence of PD. The differences in the characteristics between male hemodialysis patients with and without PD provide new insights into the pathophysiology and therapeutic window of PD.

Treatment of Peyronie’s Disease: 2012 Update

Peyronie's disease (PD) is the occurrence of a fibrous inelastic scar of the tunica albuginea of the penis. It is a relatively common disorder among men, with a reported prevalence of 3% to 8%. It is often associated with penile pain, anatomical deformities in the erect state, and difficulty with intromission. Because the exact pathophysiology of PD remains unknown and standards for evaluating or reporting treatment outcomes are unclear, research on effective therapies has been limited. The benefits of nonsurgical treatment options are conflicting and further controlled studies are required before any therapy can be fully recommended. The success of surgery has been well documented; however, surgery is invasive and costly and carries potential side effects. Patients who report stable disease that has been present for longer than 12months and who experience penile deformity preventing satisfactory sexual intercourse are best suited for surgery. Additionally, failed conservative management and a patient's preference for definitive correction are important additional indications for surgical treatment.

Rat as an animal model for Peyronie's disease research: a review of current methods and the peer-reviewed literature.

While the exact mechanism of Peyronie's disease (PD) remains an enigma, the pathophysiology of PD is considered to be multifactorial, with interactions of genetic predisposition, trauma, tissue inflammation and aberrant wound healing. A non-systematic review of the existing English language literature pertaining to the use of rodent models in the evaluation of PD was performed using the Medline database. Multiple free-text searches were performed on key words: animal models of PD, transforming growth factor β1 (TGF β1), tunical and/or corporal fibrosis, subtunical injection and penile myofibroblasts. The most frequently reported models of PD can be classified as TGF β1, fibrin and surgical trauma-induced models. In vitro studies using Peyronie's fibroblast culture media have also provided further insights into cellular mechanism of PD. At the present time, the research in PD is hampered by the lack of universally accepted animal model and this is likely attributed to the limited insight into PD mechanisms and the difficulties faced by current animal models to truly represent the complexity and complete spectrum of human disease.

Significant alterations of serum cytokine levels in patients with Peyronie's disease

To determine the expression of the cytokines transforming growth factor-beta1 (TGF-beta1), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in serum from patients with Peyronie's disease (PD) compared to healthy controls. Ninety-one consecutive PD patients aged 20 - 74 years were included in this study. All patients were diagnosed with symptomatic PD for the first time and had a palpable penile plaque. The patients previously had the disease for 6 - 72 months. None of the patients had a severe infectious disease or known systemic illness. For cytokine analyses, peripheral venous blood samples were obtained before treatment. Fifty healthy male blood donors aged 22 - 64 years served as the control group. TGF-beta1, IFN-gamma, Il-6, and TNF-alpha were analyzed quantitatively with commercial immunoassays. Mean cytokine levels in serum from patients were increased for TGF-beta1 and IFN-gamma compared to healthy controls. The difference for TGF-beta1 was considered statistically significant (p < 0.001). IL-6 was not detectable in PD patients (p < 0.01) and TNF-alpha was decreased (p < 0.0001). The significantly elevated serum level of the profibrotic TGF-beta1 cytokine underscores the effect of cytokines in the pathophysiology of PD. The significantly decreased TNF-alpha serum level suggested no acute immunomodulatory process. Therefore, the relevance for therapeutic administration of TNF-alpha should be further investigated. Quantification of TGF-beta1 in serum of PD patients provides a possible diagnostic tool and target for therapy. The data on altered cytokine levels in PD patients also provide a new understanding for etiopathogenesis of PD, which warrants further investigation.

Conservative treatment for Peyronie's disease: an update

Many theories have been proposed to explain the cause of Peyronie's disease (PD); however, the true pathogenesis of PD remains an enigma. As a result, the treatment of PD remains a dilemma and new therapies continue to evolve. The last two decades have witnessed a phenomenal advance in the understanding of the pathophysiology and natural history of PD. The efficacy of conservative treatment for PD is not settled. In this update review the authors provide information of the status of conservative therapy for PD. Conservative treatment is always the initial treatment in most of the cases. This kind of therapy consists of different modalities of treatment such as oral, intralesional or topical therapy. Other treatments including iontophoresis, extracorporeal shock wave, radiotherapy, ultrasound and laser have also been reported.

Mechanisms of Disease: new insights into the cellular and molecular pathology of Peyronie's disease

Peyronie's disease (PD) is characterized by fibrotic plaques in the penile tunica albuginea that cause curvature of the erect penis, and is often accompanied by pain and/or erectile dysfunction. This condition affects up to 9% of men. Treatment is mainly surgical, as pharmacologic therapy has limited efficacy. The pathophysiology of PD is poorly understood, but development of two rat models, extrapolation of what is known about the molecular pathology of other fibrotic conditions, and emphasis on the role of myofibroblasts and adult stem cells are helping to clarify etiology and identify new pharmacologic targets. Recent studies demonstrate a role for oxidative stress and cytokine release-primarily transforming-growth-factor beta1-in development of PD fibrotic plaques. There is evidence indicating that these profibrotic factors interact with antifibrotic defense mechanisms, such as decrease of myofibroblast accumulation, elimination of reactive oxygen species by inducible nitric oxide synthase and neutralization of transforming-growth-factor beta1 by decorin, such that some plaques are in dynamic turnover. Injury to the erect penis is thought to trigger PD by inducing extravasation of fibrin and subsequent synthesis of transforming-growth-factor beta1. Despite the lack of statistical support for a causal association between trauma and PD, it is possible that undetected microtrauma is involved. It is not known whether ossification of PD plaques is linked to fibrosis progression or is a manifestation of an alternative pathway. Both processes seem to be related to activation of fibroblast/myofibroblast differentiation in the tunica albuginea and to osteogenic commitment of stem cells in this tissue.