Peyronie's Patients Research Articles

Surgical management of complex curvature in Peyronie’s disease

PurposeAbout 10% of Peyronie's patients are complex cases with severe curvature (>60 degrees), ventral plaque, multiplanar curvature, hour-glass/hinge deformity, notching deformity, and ossified plaque. In patients with complex Peyronie’s disease (PD), different techniques (shortening procedures, lengthening procedures, and penile prosthesis implantation (IPP)) may be necessary to achieve successful result. This review aims to analyze the various surgical techniques employed in the management of Peyronie's disease, with a specific focus on patients with complex deformity.MethodsArticles focusing on the surgical management of complex curvature in Peyronie’s disease were searched in MEDLINE and PubMed published between 1990 and 2023.ResultsShortening procedures are linked to penile shortening and are not recommended for complex cases such as notching, hour-glass deformity, or ossified plaque. Lengthening procedures are suitable for addressing complex curvatures without erectile dysfunction (ED) and are a more appropriate method for multiplanar curvatures. Penile prosthesis implantation (IPP), with or without additional procedures, is the gold standard for patients with ED and Peyronie's disease. IPP should also be the preferred option for cases of penile instability (hinge deformity) and has shown high satisfaction rates in all complex cases.ConclusionWhile surgical interventions for complex curvature in Peyronie's disease carry inherent risks, careful patient selection, meticulous surgical techniques, and post-operative care can help minimize complications and maximize positive outcome.

(PM-03) EPIDEMIOLOGICAL PROFILE OF PATIENTS UNDERGOING PENILE DOPPLER ULTRASOUND AT A FEDERAL UNIVERSITY HOSPITAL IN BRAZIL

Abstract Introduction Erectile Dysfunction (ED) refers to the inability to achieve or sustain a satisfactory erection for sexual intercourse. In Brazil, the estimated prevalence of ED among adults aged 40 to 70 years is 42.1%. For the evaluation of primary erectile dysfunction and preoperative assessment of Peyronie's disease, Penile Doppler ultrasound, involving drug-induced is recommended. This study aims to provide insights into the epidemiology of patients undergoing penile Doppler ultrasound at a Federal University Hospital. Methods This retrospective study gathered data from the electronic medical records of 179 patients who underwent the examination between March 2021 and March 2023, using the Phillips Affiniti 50G device. Pharmacological induction with 10 mcg/ml Alprostadil, 30 mg/ml Papaverine, and 1 mg/ml Phentolamine. Initially, 0.1 ml of this mixture was applied to the penile shaft, with subsequent adjustments made to achieve the best maximal erection. Results The participants ages ranged from 20 to 80 years, with an average of 59.8(±11,42) years. Marital status distribution showed 139 married and 40 were single. Ethnically, there were 57 white, 69 individuals of mixed race, and 39 black. The average Body Mass Index was 26.6(±4,13). The majority of patients identified as heterosexual (174 patients), with 51 cases of hypertension and 31 cases of diabetes. Additionally, 62 patients had radical prostatectomy. Out of the 134 patients that performed the exam with the report of erectile dysfunction, 54 were diagnosed with arterial insufficiency and 09 had venous leakage. Among the 42 exlcusive clinical report of Peyronie’s, 76% exhibited a uniplanar curvature located in the dorsal region. The average curvature angle was 47°(±19,5). Conclusion Erectile dysfunction was significantly more prevalent than Peyronie's disease. Among Peyronie's patients, uniplanar curvature, especially in the dorsal region, was the most common deformity type. Financing No conflict.

BMP4 and GREM1 are targets of SHH signaling and downstream regulators of collagen in the penis.

Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED), and the Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment. We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1) and examined the relationship between SHH, BMP4, GREM1, and collagen in penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4, and GREM1 treatment. Corpora cavernosa of Peyronie's disease (control), prostatectomy, and diabetic ED patients were obtained (N= 30). Adult Sprague Dawley rats (n = 90) underwent (1) CN crush (1-7days) or sham surgery; (2) CN injury and BMP4, GREM1, or mouse serum albumin (control) treatment via Affi-Gel beads or peptide amphiphile (PA) for 14days; (3) 5E1 SHH inhibitor, IgG, or phosphate-buffered saline (control) treatment for 2 to 4days; or (4) CN crush with mouse serum albumin or SHH for 9days. Immunohistochemical and Western analysis for BMP4 and GREM1, and collagen analysis by hydroxyproline and trichrome stain were performed. BMP4 and GREM1 proteins were identified in corpora cavernosa smooth muscle of prostatectomy, diabetic, and Peyronie's patients, and in rat smooth muscle, sympathetic nerve fibers, perineurium, blood vessels, and urethra. Collagen decreased 25.4% in rats with CN injury and BMP4 treatment (P = .02) and increased 61.3% with CN injury and GREM1 treatment (P = .005). Trichrome stain showed increased collagen in rats treated with GREM1. Western analysis identified increased BMP4 and GREM1 in corpora cavernosa of prostatectomy and diabetic patients, and after CN injury (1-2days) in our rat model. Localization of BMP4 and GREM1 changed with SHH inhibition. SHH treatment increased the monomer form of BMP4 and GREM1, altering their range of signaling. A better understanding of penile remodeling and how fibrosis occurs with loss of innervation is essential for development of novel ED therapies. The relationship between SHH, BMP4, GREM1, and collagen is complex in the penis. BMP4 and GREM1 are downstream targets of SHH that impact collagen and may be useful in collaboration with SHH to prevent penile remodeling and ED.

Sonic Hedgehog Signaling in Primary Culture of Human Corpora Cavernosal Tissue From Prostatectomy, Diabetic, and Peyronie's Patients

BackgroundCavernous nerve (CN) injury causes penile remodeling, including smooth muscle apoptosis and increased collagen, which results in erectile dysfunction (ED), and prevention of this remodeling is critical for novel ED therapy development. AimWe developed 2 peptide amphiphile (PA) hydrogel delivery vehicles for Sonic hedgehog (SHH) protein to the penis and CN, which effectively suppress penile distrophic remodeling (apoptosis and fibrosis), in vivo in a rat CN injury model, and the aim of this study is to determine if SHH PA can be used to regenerate human corpora cavernosal smooth muscle deriving from multiple ED origins. MethodsCorpora cavernosal tissue was obtained from prostatectomy, diabetic, hypertension, cardiovascular disease and Peyronie's (control) patients (n = 21). Primary cultures (n = 21) were established, and corpora cavernosal cells were treated with SHH protein, MSA (control), 5E1 SHH inhibitor, and PBS (control). Growth was quantified by counting the number of cells at 3–4 days. Statistics were performed by ANOVA with Scheffe's post hoc test. Concentration of SHH protein for maximal growth was optimized, and a more active SHH protein examined. OutcomesCultures were characterized by immunohistochemical analysis with ACTA2, CD31, nNOS and P4HB, and smooth muscle was quantified in comparison to DAPI. ResultsCultures established were >97% smooth muscle. SHH protein increased growth of smooth muscle cells from prostatectomy, diabetic, and Peyronie's patients in a similar manner (49%–51%), and SHH inhibition decreased growth (20%–33%). There was no difference in growth using 25 ug and 10 ug SHH protein, suggesting a threshold concentration of SHH protein above which smooth muscle growth is enhanced. A more active lipid modified SHH peptide further enhanced growth (15%), indicating a more robust growth response. SHH increased growth in smooth muscle cells from hypertension (37%) and cardiovascular disease (32%) patients. SHH protein increased growth under normal and high glucose conditions, suggesting that high glucose conditions that may be present in under controlled diabetic patients would not detract from SHH regenerative capacity. Clinical ImplicationsSHH PA would be beneficial to enhance smooth muscle regeneration in patients with ED of multiple etiologies. Strengths and LimitationsUnderstanding how human corpora cavernosal tissue responds to SHH treatment is critical for clinical translation of SHH PA to ED patients. ConclusionCorpora cavernosal smooth muscle from all ED patients responded to SHH treatment with increased growth.Stupp, SI. Sonic Hedgehog Signaling in Primary Culture of Human Corpora Cavernosal Tissue From Prostatectomy, Diabetic, and Peyronie's Patients. J Sex Med 2022;19:1228–1242.

Sonic hedgehog signaling in corpora cavernosal cells from prostatectomy, diabetic, hypertension and Peyronie's patients with erectile dysfunction

ABSTRACT Introduction Erectile dysfunction (ED) treatments are minimally effective in prostatectomy and diabetic patients due to injury to the cavernous nerve. With denervation the critical smooth muscle undergoes apoptosis and the penis becomes fibrotic, thus altering corpora cavernosal architecture. In order to devise novel ED therapies, prevention of corpora cavernosal remodeling is critical. Sonic hedgehog (SHH) treatment by peptide amphiphile (PA) nanofiber hydrogel, suppresses smooth muscle apoptosis and improves erectile function in a rat CN injury ED model. We examine if human corpora cavernosal smooth muscle responds in a similar manner to SHH treatment. Objective In this study we: 1.) Examine if human corpora cavernosal smooth muscle cells from primary culture of ED patient tissues, respond to Sonic hedgehog (SHH) treatment by increasing growth rate, as in our in vivo animal model. 2.) Determine if human corpora cavernosal cells from patients with differing underlying mechanisms of ED development (prostatectomy, diabetes, hypertension, cardiovascular disease), respond similarly to SHH treatment. 3.) Identify if organ culture conditions (glucose) affect growth of corpora cavernosal smooth muscle and the response to SHH signaling. 4.) Examine the vascular component of ED (hypertension and cardiovascular disease). Methods Human corpora cavernosal tissue was obtained from prostatectomy, diabetic, hypertension, cardiovascular disease and Peyronie's (control) patients (n=40) that were under going prosthesis implant to treat ED. Primary cultures (n=17) were established, and corpora cavernosal cells from passage 3-4 were treated with SHH protein, MSA (control), 5E1 SHH inhibitor, and PBS (control). Growth was quantified by counting the number of cells using a hemocytometer at 3-4 days. The concentration of SHH protein for maximal growth was examined, in addition to a lipid modified more active SHH peptide. Results SHH treatment increased smooth muscle growth in human corpora cavernosal cells from prostatectomy, diabetic, and Peyronie's patients in a similar manner (43-53%). SHH inhibition decreased smooth muscle growth (24-32%). There was no difference in growth using 25ug and 10ug SHH peptide. A more active (150X) SHH peptide further enhanced growth (20%). SHH protein increased growth more in diabetic smooth muscle under high glucose conditions. SHH inhibition was less effective under high glucose conditions. SHH treatment increased growth less in cells from hypertension and cardiovascular disease patients. Conclusion Corpora cavernosa smooth muscle from prostatectomy, diabetic, and Peyronie's patients increased in response to SHH treatment in a similar manner, suggesting that SHH treatment would be beneficial to enhance smooth muscle regeneration in patients with ED of multiple origins. There is a threshold concentration of SHH protein above which smooth muscle growth is enhanced. Lipid modified SHH engendered a more robust growth response. High glucose conditions that may be present in under controlled diabetic patients would not detract from SHH usefulness as a protectant for corpora cavernosal morphology. Understanding how human corpora cavernosal tissue responds to SHH treatment is critical for clinical translation to ED patients. Disclosure Work supported by industry: no.

Pathway enrichment analysis of microarray data from human penis of diabetic and Peyronie's patients, in comparison with diabetic rat erectile dysfunction models

ABSTRACT Introduction Erectile dysfunction (ED) is a debilitating medical condition in which current treatments are minimally effective in diabetic patients due to neuropathy of the cavernous nerve, a peripheral nerve that innervates the penis. Loss of innervation causes apoptosis of penile smooth muscle, remodeling of corpora cavernosa (penile erectile tissue) morphology, and ED. Objective In this study, microarray and pathway analysis were used to obtain a global understanding of how signaling mechanisms are altered in diabetic patients and animal models as ED develops, in order to identify novel targets for disease management, and points of intervention for clinical therapy development. Methods Human corpora cavernosal tissue was obtained from diabetic (n=4) and Peyronie's (control, n=3) patients that were undergoing prosthesis implant to treat ED. Rat tissue was obtained from BB/WOR diabetic (n=5) and diabetes resistant (n=5) rats. RNA was extracted using TRIzol, DNase treated, and purified by Qiagen mini kit. Microarray was performed using the Human Gene 2.0 ST Array. 1) Alterations in patient and diabetic rat pathway signaling were examined using several analytical tools (ShinyGO, Metascape, WebGestalt, STRING) and databases, 2) Strengths/weaknesses of the different pathway analysis tools were compared, and 3) Comparison of human and rat (BB/WOR and Streptozotocin) pathway analysis was performed. Two technical replicates were performed. P value (FDR) < 0.15 was used as threshold for differential expression. FDR<0.05 was considered significant. Results Microarray identified 182 differentially expressed protein-coding genes. Pathway analysis revealed similar enrichments with different analytical tools. Down regulated pathways include development, tubular structure, sprouting, cell death, ischemia, angiogenesis, transcription, second messengers, and stem cell differentiation. ED patients, who have diabetes, incur significant loss of normal regulatory processes required for repair and replacement of injured corpora cavernosal tissue. Combined with loss of apoptotic regulatory mechanisms, this results in significant architectural remodeling of the corpora cavernosa, and loss of regenerative capacity in the penis. Conclusions Penis from diabetic ED patients lacks capacity for maintenance of corpora cavernosal architecture and regeneration, which are critical points for intervention for therapy development. The analysis of tissue specific gene expression profiles provides a means of understanding drivers of disease and identifying novel pathways for clinical intervention. This first report of microarray and pathway analysis in human corpora cavernosa, is critical for identification of novel pathways pertinent to ED and for validating animal models. Disclosure Work supported by industry: no.

Sonic Hedgehog Signaling in Corpora Cavernosal Cells from Prostatectomy, Diabetic, Hypertension and Peyronie's Patients with Erectile Dysfunction

ABSTRACT Introduction Erectile dysfunction (ED) treatments are minimally effective in prostatectomy and diabetic patients due to injury to the cavernous nerve. With denervation the critical smooth muscle undergoes apoptosis and the penis becomes fibrotic, thus altering corpora cavernosal architecture. In order to devise novel ED therapies, prevention of corpora cavernosal remodeling is critical. Sonic hedgehog (SHH) treatment by peptide amphiphile (PA) nanofiber hydrogel, suppresses smooth muscle apoptosis and improves erectile function in a rat CN injury ED model. We examine if human corpora cavernosal smooth muscle responds in a similar manner to SHH treatment. Objective In this study we: 1.) Examine if human corpora cavernosal smooth muscle cells from primary culture of ED patient tissues, respond to Sonic hedgehog (SHH) treatment by increasing growth rate, as in our in vivo animal model. 2.) Determine if human corpora cavernosal cells from patients with differing underlying mechanisms of ED development (prostatectomy, diabetes, hypertension, cardiovascular disease), respond similarly to SHH treatment. 3.) Identify if organ culture conditions (glucose) affect growth of corpora cavernosal smooth muscle and the response to SHH signaling. 4.) Examine the vascular component of ED (hypertension and cardiovascular disease). Methods Human corpora cavernosal tissue was obtained from prostatectomy, diabetic, hypertension, cardiovascular disease and Peyronie's (control) patients (n=40) that were under going prosthesis implant to treat ED. Primary cultures (n=17) were established, and corpora cavernosal cells from passage 3-4 were treated with SHH protein, MSA (control), 5E1 SHH inhibitor, and PBS (control). Growth was quantified by counting the number of cells using a hemocytometer at 3-4 days. The concentration of SHH protein for maximal growth was examined, in addition to a lipid modified more active SHH peptide. Results SHH treatment increased smooth muscle growth in human corpora cavernosal cells from prostatectomy, diabetic, and Peyronie's patients in a similar manner (43-53%). SHH inhibition decreased smooth muscle growth (24-32%). There was no difference in growth using 25ug and 10ug SHH peptide. A more active (150X) SHH peptide further enhanced growth (20%). SHH protein increased growth more in diabetic smooth muscle under high glucose conditions. SHH inhibition was less effective under high glucose conditions. SHH treatment increased growth less in cells from hypertension and cardiovascular disease patients. Conclusions Corpora cavernosa smooth muscle from prostatectomy, diabetic, and Peyronie's patients increased in response to SHH treatment in a similar manner, suggesting that SHH treatment would be beneficial to enhance smooth muscle regeneration in patients with ED of multiple origins. There is a threshold concentration of SHH protein above which smooth muscle growth is enhanced. Lipid modified SHH engendered a more robust growth response. High glucose conditions that may be present in under controlled diabetic patients would not detract from SHH usefulness as a protectant for corpora cavernosal morphology. Understanding how human corpora cavernosal tissue responds to SHH treatment is critical for clinical translation to ED patients. Disclosure No

Pathway Enrichment Analysis of Microarray Data from Human Penis of Diabetic and Peyronie's Patients, in Comparison with Diabetic Rat Erectile Dysfunction Models

ABSTRACT Introduction Erectile dysfunction (ED) is a debilitating medical condition in which current treatments are minimally effective in diabetic patients due to neuropathy of the cavernous nerve, a peripheral nerve that innervates the penis. Loss of innervation causes apoptosis of penile smooth muscle, remodeling of corpora cavernosa (penile erectile tissue) morphology, and ED. Objective In this study, microarray and pathway analysis were used to obtain a global understanding of how signaling mechanisms are altered in diabetic patients and animal models as ED develops, in order to identify novel targets for disease management, and points of intervention for clinical therapy development. Methods Human corpora cavernosal tissue was obtained from diabetic (n=4) and Peyronie's (control, n=3) patients that were undergoing prosthesis implant to treat ED. Rat tissue was obtained from BB/WOR diabetic (n=5) and diabetes resistant (n=5) rats. RNA was extracted using TRIzol, DNase treated, and purified by Qiagen mini kit. Microarray was performed using the Human Gene 2.0 ST Array. 1) Alterations in patient and diabetic rat pathway signaling were examined using several analytical tools (ShinyGO, Metascape, WebGestalt, STRING) and databases, 2) Strengths/weaknesses of the different pathway analysis tools were compared, and 3) Comparison of human and rat (BB/WOR and Streptozotocin) pathway analysis was performed. Two technical replicates were performed. P value (FDR) < 0.15 was used as threshold for differential expression. FDR<0.05 was considered significant. Results Microarray identified 182 differentially expressed protein-coding genes. Pathway analysis revealed similar enrichments with different analytical tools. Down regulated pathways include development, tubular structure, sprouting, cell death, ischemia, angiogenesis, transcription, second messengers, and stem cell differentiation. ED patients, who have diabetes, incur significant loss of normal regulatory processes required for repair and replacement of injured corpora cavernosal tissue. Combined with loss of apoptotic regulatory mechanisms, this results in significant architectural remodeling of the corpora cavernosa, and loss of regenerative capacity in the penis. Conclusions Penis from diabetic ED patients lacks capacity for maintenance of corpora cavernosal architecture and regeneration, which are critical points for intervention for therapy development. The analysis of tissue specific gene expression profiles provides a means of understanding drivers of disease and identifying novel pathways for clinical intervention. This first report of microarray and pathway analysis in human corpora cavernosa, is critical for identification of novel pathways pertinent to ED and for validating animal models. Disclosure No

Pathway Enrichment Analysis of Microarray Data Fom Human Penis of Diabetic and Peyronie's Patients, in Comparison With Diabetic Rat Erectile Dysfunction Models

BackgroundErectile dysfunction (ED) is a debilitating medical condition in which current treatments are minimally effective in diabetic patients due to neuropathy of the cavernous nerve, a peripheral nerve that innervates the penis. Loss of innervation causes apoptosis of penile smooth muscle, remodeling of corpora cavernosa (penile erectile tissue) morphology, and ED. AimIn this study, microarray and pathway analysis were used to obtain a global understanding of how signaling mechanisms are altered in diabetic patients and animal models as ED develops, in order to identify novel targets for disease management, and points of intervention for clinical therapy development. Methods and OutcomesHuman corpora cavernosal tissue was obtained from diabetic (n = 4) and Peyronie's (control, n = 3) patients that were undergoing prosthesis implant to treat ED, and BB/WOR diabetic (n = 5) and resistant (n = 5) rats. RNA was extracted using TRIzol, DNase treated, and purified by Qiagen mini kit. Microarray was performed using the Human Gene 2.0 ST Array. (i) Alterations in patient and diabetic rat pathway signaling were examined using several analytical tools (ShinyGO, Metascape, WebGestalt, STRING) and databases, (ii) Strengths/weaknesses of the different pathway analysis tools were compared, and (iii) Comparison of human and rat (BB/WOR and Streptozotocin) pathway analysis was performed. Two technical replicates were performed. P value (FDR) < .15 was used as threshold for differential expression. FDR < 0.05 was considered significant. ResultsMicroarray identified 182 differentially expressed protein-coding genes. Pathway analysis revealed similar enrichments with different analytical tools. Down regulated pathways include development, tubular structure, sprouting, cell death, ischemia, angiogenesis, transcription, second messengers, and stem cell differentiation. ED patients, who have diabetes, incur significant loss of normal regulatory processes required for repair and replacement of injured corpora cavernosal tissue. Combined with loss of apoptotic regulatory mechanisms, this results in significant architectural remodeling of the corpora cavernosa, and loss of regenerative capacity in the penis. Clinical TranslationThis first report of microarray and pathway analysis in human corpora cavernosa, is critical for identification of novel pathways pertinent to ED and for validating animal models. Strengths and LimitationsThe analysis of tissue specific gene expression profiles provides a means of understanding drivers of disease and identifying novel pathways for clinical intervention. ConclusionPenis from diabetic ED patients lacks capacity for maintenance of corpora cavernosal architecture and regeneration, which are critical points for intervention for therapy development.Searl T, Ohlander S, McVary KT, et al., Pathway Enrichment Analysis of Microarray Data Fom Human Penis of Diabetic and Peyronie's Patients, in Comparison With Diabetic Rat Erectile Dysfunction Models. J Sex Med 2022;19:37–53.

084 Sonic Hedgehog Signaling in Corporal Cavernosal Cells from Prostatectomy, Diabetic, Hypertension and Peyronie's Patients with ED

Erectile dysfunction (ED) treatments are minimally effective in prostatectomy and diabetic patients due to injury to the cavernous nerve. With denervation the critical smooth muscle undergoes apoptosis and the penis becomes fibrotic, thus altering the corpora cavernosal architecture. In order to devise novel ED therapies, prevention of corpora cavernosal remodeling is critical. In this study we examine the response of human corpora cavernosal cells from several ED patient populations, to determine if ED deriving from other underlying mechanisms than prostatectomy, are responsive to SHH treatment, and we examine other potential signaling molecules critical for smooth muscle growth and regeneration.

Is high levels of vitamin D a new risk factor for Peyronie's disease?

The aim of this study is to investigate whether serum vitamin D level predicts the risk of Peyronie's disease. Calcium and inflammatory cytokines play an important role during fibrocalcification of the plaques in Peyronie's Disease. TGF-β1 is one of the most fibrogenic cytokines. Increasing serum vitamin D levels is considered that induce expression of TGF-β1. Serum vitamin D levels and TGF-β1 are related with calcifications of some soft tissues in previous studies. One hundred and three Peyronie patients and 162 healthy volunteers were included in the study. In both groups, demographic data, medical history, physical examination and erectile capacity were recorded. Serum 25-hydroxyvitamin D, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and testosterone levels were measured. The mean level of serum 25 (OH) D was significantly higher in men with Peyronie's disease compared with the controls (32.6±7.9ng/ml vs. 18.5±6.6ng/ml respectively. p<0.001). There is a relationship between Peyronie's disease and high serum vitamin D levels. Also, increased low-density lipoprotein and total cholesterol levels, diabetes mellitus, and cardiovascular diseases were associated with Peyronie's disease.

Levels of serum trace elements in patients with Peyronie

Aim: The etiology of the disease of Peyronie is not certainly known. However, penile micro traumas are thought to be important in the pathogenesis of Peyronie’s disease (PD) in genetically predisposed individuals. In this study, we aimed to determine the relationship of some trace element and heavy metals with PD.Material and methods: Thirty Peyronie patients and 26 healthy volunteers were included in the study. In individuals in both groups, levels of serum trace elements (Manganese [Mn], Cu, Cobalt (Co), zinc [Zn], Cd, and iron [Fe]) were determined separately by Atomic Absorption Spectrophotometer method in Yüzüncü Yıl University Central Research Laboratory.Results: Mn, Cu, Zn, and Fe levels in Peyronie patients were statistically significantly lower when compared to the healthy control group (p < .05). Cd and Co levels were similar for both groups but not statistically significant (p > .05).Conclusions: The changes in trace element levels are related to the etiopathogenesis of PD. We think that our study is the first from this aspect.

Peyronie’s disease: A “triple oxygenant therapy”

To evaluate the effects of upregulators of nitric oxide in one patient with Peyronie’s disease, after non significant improvement following intracavernosal verapamil. A 20-years-old Caucasian male presented with penile induration in flaccid state, persistent during erection and associated with mild pain at third middle of penis. After treatment with intracavernosal verapamil for 4 months with relief of penile discomfort, followed by counseling on the use of penile extender for at least 6 hours per day, he was prescribed pentoxifylline associated with tadalafil plus levo-arginine, propionil-carnitine and Vitamin B3. After almost 2 years, the septal thickness was reduced at ultrasound evaluation after this &ldquo;triple oxygenant therapy&rdquo;. NO-iNOS biology in Peyronie patients is the very protagonist in modulating penile fibrosis through up-regulation of NO-cGMP pathway that influences penile health by preventing and reversing fibrosis in the tunical albuginea.

The Clinical Characteristics of Peyronie’s Patients with Notching Deformity

Peyronie's patients with notching deformity represent a small percentage of disease population, and the features of these patients have not been well established yet. To analyze the characteristics of Peyronie's patients with notching deformity. Peyronie's patients with notching deformity were compared with those with other type of penile deformities with regard to clinical features. During a 13-year period, a total of 703 patients with Peyronie's disease were evaluated at our institution. The patients were divided into two groups: group I consists of Peyronie's patients with notching deformity (N = 89) and group II patients with any other kind of penile curvature (N = 614). The clinical characteristics, presence of co-morbidities including diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hypertension, and ischemic heart disease, erectile status, and penile deformities were compared between the two groups. Pure notching deformity was detected in 12.6% (N = 89) of the patients. The mean age of men was 53.1 +/- 10.2 and 52.7 +/- 10.7 years in groups I and II, respectively, (P = 0.8). The leading presenting symptom was erectile dysfunction (68.5%), followed by penile deformity (51.6%), and pain on erection (17.9%) in group I, while it was penile curvature (77.1%), erectile dysfunction (54.6%), and pain on erection (14.4%) in group II. In group I, 27 patients (30.3%) were diagnosed during a standard evaluation for erectile dysfunction. Hypertension was significantly higher in group I (25.8%) than in group II (15.4%) (P = 0.022); whereas hypercholesterolemia was more common in group II (P = 0.008). There was no significant correlation between the presence or the number of co-morbid conditions and the presence of the notching deformity. Combined injection and stimulation test revealed a diminished erectile capacity in 46.1% of the patients in group I, while it was 31.7% in group II (P = 0.008). In group I, 62.9% had unilateral notching deformity, 34.8% had hourglass deformity, and 2.2% had combined hourglass and notching deformity. Overall, the notching deformity was localized in the distal penile shaft in 50.5%, proximal shaft in 40.4%, and mid-shaft in 8.9% of the patients in group I. In this large-scale series, pure notching deformity was detected in about one-tenth of patients with Peyronie's disease. Patients presented at the first half of the sixth decade of life and more than half of the patients were in the acute phase of the disease. The most common presenting symptom was erectile dysfunction. The notching deformity was more frequently localized at the base and tip of the penis.

Incidentally diagnosed Peyronie's disease in men presenting with erectile dysfunction.

The aim of this study was to analyze characteristics of patients with Peyronie's disease (PD) diagnosed during a standard evaluation for erectile dysfunction (ED) and compare them with patients presenting with the classical complaints of PD. During a 10-y period, a total of 448 patients were evaluated at our two outpatient clinics, directed by the same author (AK). They were divided into two groups: group I consisted of patients, who presented with only ED and were unaware of their penile deformity, and group II consisted of patients with the classical features of the disease. The clinical characteristics, penile deformities, erectile status and the presence of comorbidities were determined in the two groups. Of 448 Peyronie's patients, 16% (n=71) were detected during diagnostic work-up for ED. In this group of patients, ED was the presenting symptom for a mean period of 31.3+/-9.7 months. The mean age of men was 57.54+/-8.75 and 52.21+/-10.27 y in groups I and II, respectively (P=0.0001). The mean degree of deformity was 31.5+/-12.66 degrees in group I and 41.16+/-19.14 degrees in group II (P=0.0001). In group I (n=71), 69% (n=49) of the patients had a poor erectile response to the combined injection and stimulation (CIS) test. Also, in this group, the mean degrees of deformity in CIS-positive and -negative patients were 27.05+/-12.50 and 33.80+/-12.03 degrees , respectively (P=0.033). Diabetes mellitus (40%) was the leading comorbidity in group I, while at least one comorbidity was observed in 73% of the cases (P=0.001). A remarkable percent of Peyronie's patients (16%) were detected during a standard evaluation for ED. This study analyzed, for the first time, the frequency and the characteristics of incidentally diagnosed Peyronie's patients who presented with only ED. Our data indicate that one should always consider the possibility of PD in older patients with diabetes, presenting with only ED.

Surgical approaches for advanced Peyronie's disease patients.

Surgical therapy for Peyronie's disease (PD) is reserved for patients with severe penile deformity that fails to improve with medical treatment and impedes sexual intercourse. The surgical treatment of PD consists of either correction of the penile deformity or insertion of a penile prosthesis in patients with concomitant erectile dysfunction (ED). Plaque incision/excision combined with grafting procedures or plication techniques are suitable in Peyronie's patients having an adequate penile vascular supply. When patients with Peyronie's disease have both penile deformity and ED, penile prosthesis implantation with or without excision or incision of the tunica is the current standard of care.

Epidemiology of Peyronie's disease.

Francois Gigot de la Peyronie, surgeon to Louis XV of France, has become synonymous with the rather enigmatic though not uncommon condition of Peyronie's disease (PD), a localized connective tissue disorder of the penile tunica albuginea. The true prevalence of Peyronie's disease is unknown. Therefore, we decided to perform an evaluation of existing epidemiological data. A prevalence rate of 3.2% was determined in male inhabitants of the greater Cologne area. This is much higher than revealed by the data reported up to now, thus rendering the accepted prevalence rates of 0.3% to 1% untenable. The actual prevalence of Peyronie's disease may be even higher, considering many patients' reluctance to report this embarrassing condition to their physicians. Along these lines, most clinicians note that the number of Peyronie's patients has increased since the advent of oral sildenafil. Comparably high prevalences are known for diabetes and urolithiasis, suggesting a greater frequency of this rare disease than formerly believed.

Peyronie's disease in men under age 40: characteristics and outcome.

Peyronie's disease is most commonly seen in the fifth decade of life. However, a wide range of age (20-83 y) is reported. During a 6-year period, men with Peyronie's disease presenting under the age of 40 were reviewed retrospectively and followed-up. The prevalence of Peyronie's patients presenting under age 40 was 8.2%. Their mean age was 32.47 +/- 5.37 (range: 23-39) y and 78.9% of them presented during the acute phase of the disease. Pain on erection was a part of presenting symptom complex in 52.6% and the majority (84%) had a degree of penile curvature < 60 degrees. Erectile dysfunction (ED) was present in 21% of patients, who responded well to intracavernous injection test. After a minimal 2-year follow-up, improvement in penile deformity was observed in 36.8%, and 42.1% had stable disease while 21% experienced deterioration of the penile curvature. The onset of Peyronie's disease is clinically more noisy and acute in patients presenting under age 40 and this forces the physicians to treat them more vigorously.

The genetics and immunology of Peyronie's disease.

Peyronie's disease (PD) is a condition characterized by localized and often progressive fibrosis and scarring of the penis. This condition has an unknown etiology although several hypotheses have been proposed. These include traumatic, immunologic and genetic causes. We studied the genetics and immunology of PD using both molecular biologic and molecular genetic techniques. Men (n=283) with PD were identified by retrospective chart review of one physician's office practice. These men were contacted by telephone and asked to submit to an interview and blood test for genetic studies. Simultaneously, tissue and cells collected in the laboratory were examined by Western and Northern blot analysis for examination of protein and RNA for expression of HLA. Of the first 107 men contacted, 24 were available and consented to interview and blood testing. The mean age was 60.3 y with an average duration of PD of 4.9 y. One patient had a family history of PD while no patients had Dupuytren's contracture. Twenty patients were considered to have primary disease while four were secondary. Eleven patients had tissue prepared for Northern blot analysis and nine patients were the subject of Western blot analysis. All tissue, both Peyronie's and control expressed class I MHC while no tissue expressed class II MHC. The expression of mRNA of class I MHC was equal for Peyronie's and control patients while the expression at the protein level was less in the PD patients. We conclude that PD may have multiple etiologic agents. One cannot exclude a class II MHC association but in our population, HLA DQ is not expressed. Class I MHC may be involved as the expression of class I MHC protein is different in Peyronie's patients than in controls. Genetic studies are ongoing. International Journal of Impotence Research (2000) 12, Suppl 4, S127-S132.

Treatment of Peyronie's disease with oral colchicine: long-term results and predictive parameters of successful outcome.

As recent clinical and animal studies have indicated, colchicine, with its anti-fibrotic, anti-mitotic and anti-inflammatory activities, has suppressive effects in the pathogenesis of Peyronie's disease. Oral colchicine treatment was initiated in 60 Peyronie's patients during their acute phase (mean duration of disease: 5.7 +/- 4.3 months). Long-term results, based on changes of subjective and objective criteria, were assessed and predictive factors of successful outcome were investigated. After a mean follow-up of 10.7 +/- 4.7 months, the penile deformity improved in 30%, remained unchanged in 48.3% and deteriorated in 21.7%. Pain resolved in 95%. Best results were obtained in those with no risk factor for vascular disease, presenting during the initial 6 months of disease, degree of curvature <30 degrees, no erectile dysfunction by history and positive response to combined injection and stimulation test. In conclusion since tunica albuginea is affected as a whole in Peyronie's disease, systemic oral agents, such as colchicine, may be preferred in the early phase of the disease.