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Pilot study of intra-cavernous injections of platelet-rich plasma (P-shot®) in the treatment of vascular erectile dysfunction
Abstract
Introduction
Intracavernosal injections of platelet-rich plasma (PRP) or P-shot® are increasingly proposed as a curative treatment for organic sexual dysfunction despite the lack of evidence of effectiveness.
Objectives
We conducted a pilot study to evaluate the safety and efficacy of intracavernous PRP injections in patients with vascular erectile dysfunction (ED).
Methods
Three intracavernosal injections of PRP were performed 15 days apart in 15 patients with vascular ED unresponsive to medical treatment with 5-phosphodiesterase inhibitors and/or prostaglandin E instillations or injections. Questionnaires assessing erectile function (IIEF-EF, EHS, SEP, Sexual discomfort score) were completed prior to treatment and 1, 3 and 6 months after the last injection.
Results
No side effects were noted during the study period. The IIEF-EF score was significantly improved after treatment (P < 0.001) with a gain of 5 points at 1 month, 4 points at 3 months and 3 points at 6 months (respectively P = 0.001, P = 0.003 and P = 0.022). The other questionnaires did not change significantly. In total, 20% of patients considered that the erection lasted long enough to have a sexual intercourse (SEP score) before P-shot® versus 26.7% after the treatment (P = 1).
Conclusion
This study suggests that the effect of P-Shot® remains moderate in cases of ED with vascular origin. Larger clinical studies are needed to determine the real effectiveness of this therapeutic strategy.
Level of proof
2.
... Finally, after reading the full text of the remaining 27 articles, we found that 17 articles did not meet the inclusion criteria and were excluded (reasons for exclusion included: mismatched study population, non-PRP treatment, lack of relevant outcome data). Ultimately, we included 10 literature references in this study (15)(16)(17)(18)(19)(20)(21)(22)(23)(24) (Figure 1). Among them, 7 articles were prospective non-randomized studies (6 single-arm studies and 1 double-arm study) (15,18,19,(21)(22)(23)(24), and 3 articles were RCTs (16,17,20). ...
... Ultimately, we included 10 literature references in this study (15)(16)(17)(18)(19)(20)(21)(22)(23)(24) (Figure 1). Among them, 7 articles were prospective non-randomized studies (6 single-arm studies and 1 double-arm study) (15,18,19,(21)(22)(23)(24), and 3 articles were RCTs (16,17,20). A total of 559 ED patients were analyzed. ...
... After evaluating with the MINORS scale, among the included 7 non-randomized studies, the scores of 6 singlearm studies ranged from 13 to 15 (15,18,19,21,22,24), and the score of 1 two-arm study was 22 (23), which was acceptable for our meta-analysis (Appendix 3, Table S3). Additionally, the 3 included RCT studies were assessed using the modified Jadad scale (16,17,20), with scores ranging from 6 to 7, indicating that they were all high- ...
Background
Erectile dysfunction (ED) is a prevalent condition in aging men. Meanwhile, platelet-rich plasma (PRP), an emerging treatment alternative, has demonstrated potential in mitigating symptoms associated with ED. Our research aimed to explore the safety and effectiveness of employing PRP as a treatment strategy for ED.
Methods
Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, our research involved a thorough search across multiple databases: PubMed, Web of Science, Embase, and the Cochrane Controlled Trials Register. To assess the methodological rigor of the studies selected, we applied the modified Jadad scale and the Methodological Index for Non-Randomized Studies (MINORS) scale as evaluation tools. Subsequent to these evaluations, data analysis was conducted.
Results
Our analysis included seven non-randomized studies and three randomized controlled trials (RCTs). These studies showed that the International Index of Erectile Function-Erectile Function (IIEF-EF) scores improved significantly after 1, 3, and 6 months of PRP treatment, with increases of 4.05 [95% confidence interval (CI): 2.42, 5.68; P<0.001], 3.73 (95% CI: 2.93, 4.53; P<0.001), and 3.92 (95% CI: 3.00, 4.85; P<0.001) respectively, compared to the baseline scores. Additionally, compared to the placebo group, the PRP group showed significantly higher IIEF-EF scores. PRP treatment also had a beneficial impact on minimal clinically important difference (MCID) and peak systolic velocity (PSV). However, no significant differences were found between the PRP and placebo groups in terms of erectile hardness score (EHS) [mean difference (MD) =0.63; 95% CI: 0.26, 0.99; P<0.001] or visual analog scale (VAS) pain scores (MD =0.24; 95% CI: −0.05, 0.54; P=0.11).
Conclusions
Our study results demonstrated significant efficacy and safety of PRP in treating ED. Due to the fact that most of the literature we included was single-arm studies, it was imperative for future research to provide higher-quality evidence for validation.
... We included a total of 21 articles in our analysis , comprising 11 controlled trials involving 991 patients [12][13][14][15][16][17][18][19][20][21][22]. These studies were geographically diverse, with three conducted in Italy [12,13], two in the USA [15,16] [27,28], and one each in Egypt [29], Turkey [30], China [31], and Morocco [32]. Among the single-arm trials, two studies combined PRP with another treatment modality [23, 24], while the rest focused solely on PRP therapy. ...
... Despite this, the statistical significance persisted even after sensitivity analysis, suggesting robust and stable results. In a single-arm experimental analysis of IIEF scores, Francomano, 2023 [27] emerged as the primary source of heterogeneity within the monotherapy subgroup. Upon its removal, the heterogeneity notably decreased, indicating a significant impact on the overall results, which demonstrated that the IIEF scores following PRP treatment remained statistically different from baseline scores (SMD = -0.78, ...
Background
Erectile dysfunction (ED) is a prevalent condition in urology, and studies on the effectiveness of platelet-rich plasma (PRP) for this condition have been conducted; however, the evidence remains inconclusive. This meta-analysis aimed to evaluate the effectiveness of PRP in treating ED.
Methods
On May 17, 2024, a literature search was performed and evaluated using the Cochrane method. The primary outcome measured was the International Index of Erectile Function (IIEF) score, while the secondary outcomes included Minimal Clinically Important Difference (MCID) and peak systolic velocity (PSV).
Results
A total of 12 controlled trials involving 991 patients and 11 single-arm trials with 377 patients were analyzed. The findings revealed that compared to the control group, the PRP group demonstrated better outcomes in terms of the IIEF score and MCID (SMD = 0.59 (95% CI: [0.34, 0.84]; RR = 1.94 (95% CI: [1.33, 2.83]), In the single-arm trials, a significant improvement in IIEF scores was observed following PRP treatment (SMD = -0.99 95% CI: [-1.53, 0.46]).
Conclusion
PRP appears effective in treating erectile dysfunction, but further high-quality, large-sample trials with longer follow-up are needed to fully understand its effects.
... Although these results seem encouraging, it must be stressed that the very high dosing of PDE5-Is is likely to account for at least part of the improvement as it represents a 50% increase from the previous dosing of the participants [18]. A study conducted by Schirmann et al. enrolled 15 patients affected by vascular ED who had not responded to previous treatments [24]. According to the protocol, in each of the three sessions conducted 15 days apart, the patients received a 3 mL injection of PRP Content courtesy of Springer Nature, terms of use apply. ...
... However, it is noteworthy that the EHS and SEP did not exhibit improvement following the treatment. [24]. The prospective non-randomized cohort study conducted by Francomano et al. aimed to assess the response to PDE5-Is before and after PRP injection in a cohort of 150 vasculogenic ED patients [25]. ...
Purpose
Platelet-rich plasma (PRP) as a regenerative therapy has gained interest in the field of andrology for the treatment of erectile dysfunction (ED) and Peyronie’s disease (PD). This systematic review aims to critically evaluate the current evidence on the use of PRP for these conditions.
Methods
We performed a systematic literature search according to the PRISMA guidelines using PubMed and Scopus databases in December 2023. Studies were included if they evaluated the effect of PRP therapy for ED or PD in humans.
Results
We identified 164 articles, 17 of which were included, consisting of 11 studies on ED, 5 studies on PD, and 1 study on both. We included four randomized controlled trials, 11 prospective cohort studies, and three retrospective cohort studies including a total of 1099 patients. The studies on ED and PD generally showed small to moderate benefits with mild and transient side effects and no major adverse events were reported. General limitations included variations in PRP protocols, small sample sizes, short follow-up periods, and lack of control groups except in the three randomized trials on ED and the one on PD.
Conclusion
The literature on PRP therapy in andrology is limited and difficult to interpret due to variations in protocols and methodological drawbacks. Further research is necessary to determine the optimal preparation and treatment protocols for PRP therapy and clarify its effectiveness in andrology.
... indicating a substantial enhancement in erectile function. These findings align with previous studies, such as Schirmannet al. (2022) and Shaher et al. (2023), which reported improved penile hemodynamics and increased patient satisfaction following PRP treatment [16,17] . Additionally, secondary outcomes highlighted improvements in metabolic parameters, including triglyceride and HDL levels, suggesting that PRP may exert systemic benefits beyond local tissue repair. ...
... For instance, a systematic review by Mohammad et al. demonstrated that PRP therapy could significantly enhance erectile function scores in men, paralleling the effects of other common ED treatments without accompanying systemic side effects [4]. Similarly, a review and study in 2022 consolidated evidence from multiple trials, underscoring the potential benefits of PRP injections in improving erectile function, particularly among patients with vasculogenic ED [5,6]. ...
Background
Among the emerging treatments for erectile dysfunction (ED), platelet-rich plasma (PRP), known for its ability to enhance tissue repair and regeneration, stands out as a promising therapeutic approach. In this innovative study, we aimed to assess the efficacy of intracavernous injections of platelet lysate (PL), a derivative of PRP, in improving erectile function among ED patients.
Methods
We enrolled twenty-six patients, aged between 35 and 70 years (mean age 51.6 ± 11.3 years), who had been experiencing ED for over six months and had an International Index of Erectile Function-5 (IIEF-5) score of 21 or less. Participants received autologous PL injections intracavernously every two weeks for a total of five administrations. We assessed Erection Hardness Score (EHS) and International Index of Erectile Function-5 (IIEF-5) bi-weekly for 16 weeks and conducted penile Doppler ultrasounds pre- and post-treatment to record peak systolic velocity (PSV) and resistance index (RI).
Results
Before treatment, the mean EHS was 2.15 ± 0.88 and IIEF-5 was 10.92 ± 5.28. Remarkable improvements were observed post-treatment, with the EHS significantly increasing to 3.15 ± 0.83 (p < 0.05) and IIEF-5 to 17.23 ± 5.26 (p < 0.05). Penile Doppler ultrasound exhibited an increase in both PSV and RI post-treatment, with the rise in RI being statistically significant.
Conclusions
Our findings indicate that intracavernous injections of PL substantially enhance erectile function, as evidenced by improvements in EHS, IIEF-5, and the RI of penile Doppler ultrasound, without hemorrhagic events or other adverse reactions apart from temporary pain at the injection site during the 16-week follow-up period. These encouraging results suggest that PL injections are a safe and effective treatment modality for patients with moderate ED, potentially providing a less invasive and more physiologically friendly alternative to current ED management strategies.
Trial registration
The study received approval from the Institutional Review Board of National Taiwan University Hospital (IRB Number 202008061RIPC, date of registration 08/28/2020).
... 2.5 ml is put into each side. 19 Schirman et al., 20 Every patient was administered a 2 mL solution of sodium citrate with a concentration of 3.13%, which was then combined with 23 mL of recently collected blood. In accordance with the kit instructions, Transferring the 25 mL mixture to the hourglass, it was centrifuged at 3000 rotations per minute for 3 minutes. ...
Background
Platelet-rich plasma (PRP) is a novel treatment for erectile dysfunction (ED) that is considered to be a cost-effective option. It has demonstrated positive outcomes and minimal adverse effects. By injecting PRP into the intracavernous tissue, it has the potential to promote angiogenesis and neuroregeneration, leading to a potential permanent improvement in erectile performance. The potency and safety as well as the variety of PRP administration protocols in the treatment of ED are the objectives of this paper.
Method
Using certain terms, a systematic search was done on three different databases: Science Directs, Scielo, and PubMed. Papers about PRP therapy for EDs within the last decade, be randomized controlled trials (RCTs), and be original studies with freely available full-text content were included in this study. This article omitted letters to the editor, reviews, and editorials regarding PRP and ED.
Results
Three RCT were included in this studies. The improvement is observed at one month, three months, and six months after the treatment, compared to the baseline. PRP group participants met the Minimal Clinically Important Difference (MCID) in the International Index of Erectile Function-Erectile Function (IIEF-EF) at a higher percentage than those in the placebo group at both one month and six months. Injection of PRP leads to a superior enhancement in the IIEF-EF score, compared to a placebo, in patients suffering from ED at one month, three months, six months.
Conclusion
PRP is a proven therapeutic technique that has been shown to greatly enhance ED. Yet, to establish uniform guidelines for PRP in treating erectile dysfunction, further investigation into PRP, particularly in protocol development, is imperative.
... However, overall, the existing evidence cannot conclusively determine the specific functions and mechanisms of action of PRP. Apart from these four RCTs, other relevant clinical studies that have been published have also not found any significant adverse reactions [41,42]. Although PRP itself is not problematic, some specific populations may not be suitable for PRP treatment. ...
Background
Erectile dysfunction (ED) is a common issue among males, and the use of platelet-rich plasma (PRP) therapy for treating ED has gained increasing attention, but there is still no conclusive evidence regarding its efficacy.
Aim
To evaluate the efficacy of PRP therapy for ED.
Methods
We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases up to November 2023 to identify randomized controlled trials (RCTs) on PRP therapy for ED. We used Review Manager version 5.4 for data analysis and management.
Result
After applying inclusion and exclusion criteria for screening, a total of 4 studies involving 413 patients were finally included in our meta-analysis. According to our analysis, the PRP group showed significant advantages over the placebo group in terms of MCID at the first month (p = 0.03) and sixth months (p = 0.008), while there was no significant difference between the two groups at the third month (p = 0.19). Additionally, in terms of IIEF, PRP showed significantly better efficacy than placebo at the first, third, and sixth months (p < 0.00001).
Conclusions
PRP shows more effectiveness in treating ED compared to placebo, offering hope as a potential alternative treatment for ED.
... Another pilot study was conducted recently, showing increased efficacy of PRP in the treatment of patients with ED not responding to any oral or ICI therapy. 32 Zaghloul et al 33 found that in patients with ED not responding to on-demand PDE5 inhibitor, PRP treatment in combination with daily tadalafil and on-demand vardenafil led to significant improvement in the IIEF-5 score, improved Erection Hardness Scale score, and penile duplex readings. Recently, a double-blind, sham-controlled RCT by Khalef et al 34 was published, but was not included in this review due to insufficient results presentation and a very small sham group (17 vs 42 patients). ...
Introduction:
There has been tremendous growth in regenerative medicine during the last decade. For erectile dysfunction (ED), after the inclusion of low-intensity shockwave therapy as a treatment modality for ED management by the European Association of Urology sexual health guidelines, intracavernosal injection of platelet-rich plasma (PRP) has gained popularity between urologists and patients as a novel ED therapeutic modality with initial promising results. However, limited clinical data exist regarding efficacy and safety in patients with ED. Furthermore, despite numerous preclinical studies in other tissues and organs, the mechanism of action for restoring erectile function remains undetermined.
Objectives:
This systematic review aims to present the current status of preclinical and clinical evidence regarding the use of PRP as treatment option for ED.
Methods:
A systematic literature search was conducted using PubMed, Cochrane, and ScienceDirect databases, until February 2023 for studies exploring the effect of PRP on ED.
Results:
We identified 517 articles, 23 of which were included in this review. These were 7 preclinical (of which 1 was a comparative trial and 6 were placebo-controlled randomized controlled trials) and 16 clinical studies (of which 1 was a comparative trial, 5 were randomized trials, and 2 were placebo-controlled randomized controlled trials). Preclinical data support the regenerative role of PRP in erectile tissue, in accordance with existing evidence in other tissues. Randomized clinical studies, as well as the first 2 available randomized, placebo-controlled clinical trials, showed promising efficacy and a lack of any adverse events.
Conclusion:
As PRP for ED is widely used worldwide, there is an urgent need for high-quality studies with long-term follow-up. Standardization of research protocols, especially on the quality of PRP preparation, is also needed.
... Another pilot study was conducted recently, showing increased efficacy of PRP in the treatment of patients with ED not responding to any oral or ICI therapy. 32 Zaghloul et al 33 found that in patients with ED not responding to on-demand PDE5 inhibitor, PRP treatment in combination with daily tadalafil and on-demand vardenafil led to significant improvement in the IIEF-5 score, improved Erection Hardness Scale score, and penile duplex readings. Recently, a double-blind, sham-controlled RCT by Khalef et al 34 was published, but was not included in this review due to insufficient results presentation and a very small sham group (17 vs 42 patients). ...
Penile concerns include erectile dysfunction (ED) and Peyronie disease (PD). Restorative therapies including Stem Cell Therapy (SCT) and Platelet Rich Plasma (PRP) injections are proposed to treat these concerns. SCT encompasses the harvesting and injection of mesenchymal stem cells or stromal vascular fractions from various tissue sources. PRP is derived autologously from a patient’s plasma and is then injected into the penile tissue. These therapies repair damaged penile tissue and promote both new cellular and vascular growth, as demonstrated in basic science studies. Human trials on SCT and PRP for both ED and PD and have yielded promising results with few side effects. While encouraging, small cohort size and lack of blinding or placebo control limit these studies’ external validity. Recently, the first double-blinded randomized controlled trial on PRP for ED was published, providing significant evidence of efficacy. With the rapid commercial availability of SCT and PRP for ED and PD, it is imperative to perform more randomized and placebo-controlled trials with standardized procedures and preparations to evaluate efficacy and safety. This narrative review will summarize the available literature on these penile restorative therapies to date.
Objective
Intracavernous injection might be offered to patients with erectile dysfunction (ED) who did not respond to the first-line oral treatment. Platelet-rich plasma (PRP) might offer improvement in erectile function since it contains numerous growth factors. This study aimed to evaluate the efficacy and safety of PRP intracavernous injection for patients with ED.
Methods
We conducted relevant literature searches on Cochrane Library, Medline, Scopus, and ClinicalTrials.gov databases using specific keywords. The results of continuous variables were pooled into the mean difference (MD) and dichotomous variables into the odds ratio along with 95% confidence interval (95% CI).
Results
A total of six studies were included. Our pooled analysis revealed that PRP intracavernous injection was associated with a significant increase in the erectile function domain of the International Index of Erectile Function at 1 month (MD 3.47 [95% CI 2.62–4.32], p<0.00001, I²=7%), 3 months (MD 3.19 [95% CI 2.25–4.12], p<0.00001, I²=0%), and 6 months (MD 3.21 [95% CI 2.30–4.13], p<0.00001, I²=0%) after the intervention when compared with baseline values. PRP was also superior to a placebo in terms of improvement in erectile function domain of the International Index of Erectile Function score at 1 month (MD 2.83, p<0.00001), 3 months (MD 2.87, p<0.00001), and 6 months (MD 3.20, p<0.00001) post-intervention. The adverse events from PRP injection were only mild without any serious adverse events.
Conclusion
PRP intracavernous injection may offer benefits in improving erectile function in patients with ED with a relatively good safety profile.
We aim to summarize the latest evidence on platelet-rich plasma (PRP) intracavernosal injections efficacy in men affected by primary organic erectile dysfunction (ED). We reviewed the literature for randomized controlled trials (RCTs) or prospective and retrospective comparative studies evaluating PRP alone or in combination for ED treatment. A comprehensive search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov was performed for English language full-text articles or conference abstracts. A qualitative and quantitative data synthesis was provided. Overall, seven records were included: three RCTs evaluated PRP vs. placebo, one study separately tested PRP and low-intensity shock wave therapy (Li-SWT), three studies compared Li-SWT or low-intensity pulsed ultrasound alone with their combination with PRP. Of 641 included patients, 320 received PRP. Despite the heterogeneity among inclusion criteria, dose and protocol of PRP administration, and outcomes measured, most studies independently reported better sexual outcomes in patients who received PRP, without significant severe side effects. In meta-analysis, where only placebo-controlled studies were included, patients treated with PRP showed higher International Index of Erectile Function (erectile function domain) score compared to patients who received placebo: pooled mean difference (95% Confidence Interval) of 2.99 (1.86, 4.13) after 1 month (209 patients) vs. 2.85 (1.61, 4.09) after 3 months (204 patients) vs. 3.21 (1.82, 4.60) after 6 months (199 patients) of follow-up. In men affected by primary organic ED, PRP intracavernosal injections demonstrated an objective improvement or at least a tendency in erectile function recovery. Patient numbers, and the short-term follow-up may limit the generalizability of these observations. High quality, large-scale, and standardized controlled trials are needed before recommending its definitive use in clinical practice.
Introduction
Platelet-rich plasma (PRP) is useful in the treatment of different conditions and diseases as it contains concentrated levels of many growth factors.
Aim
The aim of this study was to investigate the effectiveness of autologous PRP application in the treatment of erectile dysfunction (ED) in patients with metabolic syndrome.
Methods
In this prospective study conducted in June 2019, 31 patients with ED were included. The International Index of Erectile Function–Erectile Function domain (IIEF-EF) questionnaires were used to evaluate erectile function (EF). After administering the intracavernous autologous PRP 3 times with an interval of 15 days, IIEF-EFs were evaluated 1, 3, and 6 months later.
Main Outcome Measure
IIEF in the 1st, 3rd, and 6th months and adverse events.
Results
While the mean IIEF-EF was 18 before the application, the mean IIEF-EF was 20 in the first, third, and sixth months after the procedure (P < .001). However, even though IIEF-EF values increased numerically, median value remained within the mild-moderate classification (scores between 17 and 21). Postprocedure sexual satisfaction scores were significantly higher than preprocedure values (8 vs 6, respectively; P = .002). In the first follow-up of a patient after the 3rd injection, a 4-mm diameter fibrotic plaque was observed on the ventral side in the middle of the penis shaft.
Conclusion
In conclusion, our findings suggest that larger studies as well as placebo-controlled studies are needed to add PRP to the treatment protocol in ED.
T Taş, Çakıroğlu, E Arda, et al. Early Clinical Results of the Tolerability, Safety, and Efficacy of Autologous Platelet-Rich Plasma Administration in Erectile Dysfunction. Sex Med 2021; XX:XXX–XXX.
The overall increase of chronic degenerative diseases associated with ageing makes wound care a tremendous socioeconomic burden. Thus, there is a growing need to develop novel wound healing therapies to improve cutaneous wound healing. The use of regenerative therapies is becoming increasingly popular due to the low-invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining interest due to its potential to stimulate and accelerate the wound healing process. The cytokines and growth factors forming PRP play a crucial role in the healing process. This article reviews the emerging field of skin wound regenerative therapies with particular emphasis on PRP and the role of growth factors in the wound healing process.
Purpose:
Autologous platelet rich plasma (PRP) is used increasingly in a variety of settings. PRP injections have been used for decades to improve angiogenesis and wound healing. They have also been offered commercially in urology with little to no data on safety or efficacy. PRP could theoretically improve multiple urologic conditions, such as erectile dysfunction (ED), Peyronie's disease (PD), and stress urinary incontinence (SUI). A concern with PRP, however, is early washout, a situation potentially avoided by conversion to platelet rich fibrin matrix (PRFM). Before clinical trials can be performed, safety analysis is desirable. We reviewed an initial series of patients receiving PRFM for urologic pathology to assess safety and feasibility.
Materials and methods:
Data were reviewed for patients treated with PRFM at our center from November 2012 to July 2017. Patients were observed immediately post-injection and at follow-up for complications and tolerability. Where applicable, International Index of Erectile Function (IIEF-5) scores were reviewed before and after injections for ED and/or PD. Pad use data was collected pre/post injection for SUI.
Results:
Seventeen patients were identified, with a mean receipt of 2.1 injections per patient. Post-procedural minor adverse events were seen in 3 men, consisting of mild pain at injection site and mild penile bruising. No patients experienced complications at follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations.
Conclusions:
PRFM appears to be a safe and feasible treatment modality in patients with urologic disease. Further placebo-controlled trials are warranted.
Introduction:
Erectile dysfunction (ED) is an important health concern that can significantly affect a man's psychosocial well-being. ED has traditionally been considered a disease of old age; however, contemporary evidence suggests a growing incidence of ED in men younger than 40 years. The process of achieving an erection is multifaceted; there are many potential mechanisms that can be disrupted. It is critical to identify the specific causes of ED before proceeding with potentially costly and invasive therapeutic options. Advances in diagnostic and treatment modalities offer opportunities to identify and manage young men with ED.
Aim:
To provide an update on the prevalence and risk factors of ED in young men and to provide a framework to guide clinicians in identifying and managing the affected young man.
Methods:
Comprehensive review of the literature pertaining to ED in young men.
Main outcome measures:
ED in young men was assessed by outlining the prevalence according to recent epidemiologic studies. The pathophysiology, diagnostic considerations, risk factors, and etiologies were reviewed.
Results:
Large multinational studies have estimated the prevalence of ED in young men to be as high as 30%. Several studies have stratified the etiologies of ED into psychogenic and organic causes. Psychogenic etiologies of ED include depression, anxiety, and partner-related difficulties. These patients tend to experience sudden onset of symptoms, with decreased libido and good quality of spontaneous or self-stimulated erections. Organic etiologies include vasculogenic, endocrinologic, neurogenic, iatrogenic, and structural components. These patients usually experience gradual onset of symptoms and a low to normal libido. Conservative treatments such as phosphodiesterase type 5 inhibitors continue to be the mainstay treatment.
Conclusions:
ED in young men is an increasingly common condition. A careful diagnostic evaluation should focus on the identification of any underlying etiology to ensure appropriate management of patients. Nguyen HMT, Gabrielson AT, Hellstrom WJG. Erectile Dysfunction in Young Men-A Review of the Prevalence and Risk Factors. Sex Med Rev 2017;5:508-520.
Background/aim Significant biological differences in platelet-rich plasma (PRP) preparations have been highlighted and could explain the large variability in the clinical benefit of PRP reported in the literature. The scientific community now recommends the use of classification for PRP injection; however, these classifications are focused on platelet and leucocyte concentrations. This presents the disadvantages of (1) not taking into account the final volume of the preparation; (2) omitting the presence of red blood cells in PRP and (3) not assessing the efficiency of production.
Methods On the basis of standards classically used in the Cell Therapy field, we propose the DEPA (Dose of injected platelets, Efficiency of production, Purity of the PRP, Activation of the PRP) classification to extend the characterisation of the injected PRP preparation. We retrospectively applied this classification on 20 PRP preparations for which biological characteristics were available in the literature.
Results Dose of injected platelets varies from 0.21 to 5.43 billion, corresponding to a 25-fold increase. Only a Magellan device was able to obtain an A score for this parameter. Assessments of the efficiency of production reveal that no device is able to recover more than 90% of platelets from the blood. Purity of the preparation reveals that a majority of the preparations are contaminated by red blood cells as only three devices reach an A score for this parameter, corresponding to a percentage of platelets compared with red blood cells and leucocytes over 90%.
Conclusions These findings should provide significant help to clinicians in selecting a system that meets their specific needs for a given indication.
Background: Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction.
Methods: Seventeen men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5–18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study is registered with ClinicalTrials.gov, NCT02240823.
Findings: Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered their erectile function and were able to accomplish sexual intercourse. Post-hoc stratification according to urinary continence status was performed. Accordingly, for continent men (median IIEFinclusion = 7 (95% CI 5–12), 8 out of 11 men recovered erectile function (IIEF6months = 17 (6–23)), corresponding to a mean difference of 0.57 (0.38–0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5–6); mean difference 1 (95% CI 0.85–1.18), p > 0.9999).
Interpretation: In this phase I trial a single intracavernosal injection of freshly isolated autologous ADRCs was a safe procedure. A potential efficacy is suggested by a significant improvement in IIEF-5 scores and erectile function. We suggest that ADRCs represent a promising interventional therapy of ED following prostatectomy.
Funding: Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society.
Platelet-rich plasma (PRP) containing autologous growth factors is applied in regenerative medicine, but the lack of an optimized PRP preparation protocol causes unstable therapeutic effects. The aim of this study was to optimize the PRP preparation method and compare the effects of PRP from different preparation methods in restoration of erectile function in a rat model. The in vivo experiments used Sprague-Dawley male rats (n = 24), which were randomly divided into four groups of equal numbers: group I underwent sham operation, while the remaining three groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of general PRP, optimized PRP [with the largest amount of platelet-derived growth factor (PDGF)-AB] or normal saline-only injection in the corpus cavernosum, respectively. Four weeks later, erectile function was assessed by CN electrosimulation, and penile tissue was collected for histology. Results demonstrated that in the PRP group prepared with the ACD-A anticoagulant, chitosan and incubated at -20°C for 15 days had the largest amount of PDGF-AB and showed a synergistic effect on release (p < 0.05). Functional outcome measurement and immunofluorescence staining for the dorsal nerve revealed that improvement after bilateral CN injury occurred in the optimized PRP group (p < 0.05). It was concluded that optimized PRP with a high level of growth factors was more stable, and its injection into the corpus cavernosum facilitated recovery of erectile function. Copyright © 2013 John Wiley & Sons, Ltd.
Introduction. Neurogenic erectile dysfunction resulting from cavernous nerve (CN) injury is a major complication caused by radical prostatectomy. The use of platelet-rich plasma (PRP) on the nerve-injured site has shown promising results for the nerve regeneration. However, the effects of PRP injection in corpus cavernosum after bilateral CN injury have never been investigated.
Aim. To assess the neuroprotective effect of PRP injection in corpus cavernosum after bilateral CN injury.
Methods. Male Sprague-Dawley rats were randomly divided into three groups: Group I underwent sham operation, while the remaining two groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of PRP or normal saline only injection in the corpus cavernosum, respectively. Four weeks later, erectile function (EF) was assessed by CN electrosimulation, and CNs as well as penile tissue were collected for histology.
Main Outcome Measures. Intracavernous pressure (ICP) monitored during electrical stimulation of CNs; myelinated axons number of CNs and dorsal penile nerve; collagen type change, number of apoptotic cells, and mRNA expression of caspase-3 and transforming growth factor-β1 (TGF-β1) in the corpus cavernosum.
Results. Four weeks after surgery, in the vehicle-only group, the functional evaluation showed a lower mean maximal ICP than that in the sham group (P < 0.05). PRP treatments resulted in significant recovery of EF, as compared with the vehicle-only group (P < 0.05). Histologically, the PRP-treated group had a significant preservation of myelinated axons of CNs compared with the vehicle-only group (P < 0.05) and reduced the apoptotic index. The mRNA expression of TGF-β1 in the corpus cavernosum tissue was significantly decreased in the PRP group compared with the vehicle-only group (P < 0.05).
Conclusions. PRP injection in the corpus cavernosum increased the number of myelinated axons and facilitated recovery of EF in the bilateral CN injury rat model. Wu C-C, Wu Y-N, Ho H-O, Chen K-C, Sheu M-T, and Chiang H-S. The neuroprotective effect of platelet-rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med 2012;9:2838–2848.
Introduction
Animal studies postulate that platelet-rich plasma (PRP) injections improve key elements of the pathophysiologic mechanisms leading to erectile dysfunction (ED).
Objectives
To conduct the first double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of PRP injections in patients with mild and moderate ED.
Methods
Sixty sexually active patients with mild and moderate ED were randomly assigned to two sessions, with a one-month difference, of 10 mL PRP (n=30) or placebo (n=30) intracavernosal injections. An FDA-approved separation system was used. Patients were evaluated at one, three and six months after completion of the treatment protocol. A per-protocol analysis was applied. All participants withheld any ED treatment during the trial. The primary outcome was the achievement of minimal clinically important difference (MCID) in the International Index of Erectile Function – Erectile Domain (IIEF-EF) from baseline to six months after final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated.
Results
At six months, a MCID was achieved by 20/29 (69%) patients in the PRP group compared to 7/26 (27%) in the placebo group. The risk difference between the two groups was 42% (95%CI: 18-66), p<0.001 and the baseline-adjusted mean between-group-difference in the IIEF-EF score was 3.9 points (95%CI: 1.8-5.9). Similarly, a statistically significant difference of both the number of participants attaining a MCID and the IIEF-EF score was also observed at the one- and three-month evaluation between the two groups. Accordingly, patients receiving PRP were more satisfied with the treatment. No adverse events were observed during the study period.
Conclusions
Intracavernosal PRP injection therapy used as outlined in this trial appears to be a safe and effective short-term treatment for the management of mild to moderate ED. Therefore, it may be a promising addition to the urologist's armamentarium for the management of ED. Still, further high-quality studies are warranted to corroborate our findings.
Disclosure
Work supported by industry: no.
Introduction:
Erectile Dysfunction (ED) and Peyronie's Disease (PD) are debilitating medical conditions affecting patients' quality of life (QoL). Platelet-rich plasma (PRP) injections are one of the various emerging approaches proposed to treat these medical conditions.
Aim:
To describe the evidence of the potential role of PRP injections in ED and PD.
Methods:
The authors conducted a systematic review according to the PRISMA statement using the following databases in November 2019: The National Library of Medicine (PubMed), Ovid Medline, Cochrane, Scopus, Embase, and Embase classic. The search was performed using keywords drawn from studies on the use of PRP in ED and PD in clinical and preclinical studies.
Results:
Eighteen articles met the inclusion criteria for review, including 12 studies on the use of PRP in humans and 6 on the use of PRP in rats. Ten studies reported on the efficacy of PRP in ED exclusively, 7 in PD exclusively and one in both conditions. In humans, 6 and 3 studies showed promising results in PD and ED, respectively. No major complications were noted. Unwanted minor side effects were noted by studies reporting on PD, including mild penile bruising, ecchymosis, hematomas as well as transient hypotension noted in 2 out of 90 patients.
Conclusion:
PRP injections for the treatment of ED may be promising, but no recommendation can be made because of scarce evidence. Safety and effectiveness of this therapy in the treatment of ED and PD require further preclinical and clinical studies with standardized protocols to gain an adequate insight into its potential implications. Patients should be offered to be part of such trials to better understand PRP potential. MH Alkandari, N Touma, S Carrier, Platelet-Rich Plasma Injections for Erectile Dysfunction and Peyronie's Disease: A Systematic Review of Evidence. Sex Med Rev 2021;XX:XXX-XXX.
Background:
Animal studies postulate that platelet-rich plasma (PRP) injections improve key elements of the pathophysiologic mechanisms leading to erectile dysfunction (ED).
Aim:
To conduct the first double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of PRP injections in patients with mild and moderate ED.
Methods:
Sixty sexually active patients with mild and moderate ED were randomly assigned to two sessions, with a one-month difference, of 10 mL PRP (n = 30) or placebo (n = 30) intracavernosal injections. An FDA-approved separation system was used. Patients were evaluated at 1, 3 and 6 months after completion of the treatment protocol. A per-protocol analysis was applied. All participants withheld any ED treatment during the trial.
Outcomes:
The achievement of minimal clinically important difference (MCID) in the International Index of Erectile Function - Erectile Domain (IIEF-EF) from baseline to 6 months after final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated.
Results:
At 6 months, a MCID was achieved by 20/29 (69%) patients in the PRP group compared to 7/26 (27%) in the placebo group. The risk difference between the two groups was 42% (95%CI: 18-66), P < 0.001 and the baseline-adjusted mean between-group-difference in the IIEF-EF score was 3.9 points (95%CI: 1.8-5.9). Similarly, a statistically significant difference of both the number of participants attaining a MCID and the IIEF-EF score was also observed at the 1- and 3-month evaluation between the two groups. Accordingly, patients receiving PRP were more satisfied with the treatment. No adverse events were observed during the study period.
Clinical implications:
Intracavernosal PRP injection therapy used as outlined in this trial appears to be a safe and effective short-term treatment for the management of mild to moderate ED.
Strengths & limitations:
We conducted the first clinical trial exploring the role of PRP in the management of ED. Conversely, our findings lack external validity due to single-center design. Furthermore, our results cannot be extrapolated to other PRP separation systems.
Conclusions:
PRP intracavernosal injections may be a promising addition to the urologist's armamentarium for the management of ED. Still, further high-quality studies are warranted to corroborate our findings. Evangelos P, Mykoniatis I, Pyrgidis N, et al. Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2021;XX:XXX-XXX.
Introduction:
Platelet-rich plasma (PRP) found its use in treating different conditions and diseases, because concentrated plasma PRP consists of many growth factors. Their interaction with surrounding cells, intracellular matrix, and mediators at the site of injection leads to tissue regeneration. Angiogenic, vasculogenic, and regenerative effects of PRP may be used for erectile dysfunction (ED) and Peyronie's disease (PD) treatment.
Aim:
To present a current data review of preclinical and clinical trials on PRP use for treating ED and PD.
Methods:
Up-to-date literature on PRP use for ED and PD treatment was analyzed. The search was based on Pubmed, Cochrane Library, clinicaltrials.gov databases, with the following key words: "platelet-rich plasma" and/or "erectile dysfunction" and/or "Peyronie's disease" and/or "sexual dysfunction."
Main outcome measures:
The main outcome measures for preclinical trials on ED were erectile function, assessed with intracavernous pressure, and pathologic analysis of penile tissue. The main outcome measures for clinical trials on ED included penile duplex Doppler ultrasound scanning and validated questionnaires. The main outcome measures on PD were pathologic analysis of penile tissue for preclinical trials, as well as penile duplex Doppler ultrasound scanning, penile curvature angle measuring, and validated questionnaires for clinical trials.
Results:
4 preclinical and 6 clinical trials were described and analyzed in this article. Limitations for both preclinical and clinical trials included small groups, short follow-up periods, a lack of control groups or groups with placebo, and the lack of quality and quantity analysis of PRP.
Conclusion:
Available data show the lack of adverse reactions with PRP treatment. The studies that we found were limited by small groups. This is why the data on safety and effectiveness should be taken carefully. However, it is important to mention that PRP therapy has the potential for treating male sexual dysfunction and may be useful in andrology. Epifanova MV, Gvasalia BR, Durashov MA, et al. Platelet-Rich Plasma Therapy for Male Sexual Dysfunction: Myth or Reality? Sex Med Rev 2020;8:106-113.
Background: Platelet-rich plasma (PRP) injections have recently been marketed as a form of autologous cell therapy under the banner of regenerative medicine despite limited scientific evidence on its use for treating erectile dysfunction (ED). Aim: To evaluate the evidence on PRP treatment for ED and determine the current trends in provision of this treatment. Methods: A critical review of the literature on PRP using the PubMed and Embase databases. Outcomes: This narrative review focuses on the clinical use of, regulation of, and evidence for PRP in the treatment of ED. Results: There is a limited number of published peer-reviewed articles demonstrating clinical outcomes pertaining to the use of PRP for ED in human. The technique of PRP application for ED is currently patented, with a global total of 683 registered clinics. The majority of PRP clinics do not provide cost estimates on their websites. Conclusion: Despite a global presence of PRP clinics and ongoing active marketing and public interest in regenerative medicine, no scientific evidence has been published to establish an evidence-based risk-benefit profile for PRP use for ED in humans. Given the limited data on clinical efficacy and potential harmful side effects, there is a need for a proper clinical trial to examine the role of PRP before it is accepted as standard of care in treatment for ED. Scott S, Roberts M, Chung E. Platelet-Rich Plasma and Treatment of Erectile Dysfunction: Critical Review of Literature and Global Trends in Platelet-Rich Plasma Clinics. Sex Med Rev 2019;X:XXX–XXX.
Abstract
Objectives: This open label, phase I clinical trial (NCT02945462)
using 2 consecutive intracavernous autologous bone marrow-
derived mesenchymal stem cells (BM-MSCs) for the first
time in the treatment of diabetic patients with erectile dysfunction
(ED). The primary outcome is to assess the safety and
tolerability of intracavernous autologous BM-MSCs, the secondary
outcome is to assess efficacy of the procedure. Patients
and Methods: Four diabetic patients with refractory
ED were included. Two consecutive intracavernous autologous
BM-MSC injections were performed. Tolerability was assessed
immediately and at 24 h, safety was evaluated for
2 years. Efficacy was assessed using International Index of
Erectile Function-15 (IIEF-15) and Erection Hardness Score
(EHS) for 12 months. Results: procedure was well tolerated
and no patients reported significant adverse effects. There
was significant improvement of IIEF-15 and EHS; IIEF-15 ( p =
0.04), Erectile Function ( p = 0.03), Sexual Desire ( p = 0.04), Intercourse
Satisfaction ( p = 0.04), and Overall Satisfaction ( p =
0.04). Conclusion: This is the first human study with proven
tolerability, safety and efficacy of intracavernous autologous
BM-MSC injections for treatment of diabetic patients with ED.
We recently reported stage I of a phase 1/2 clinical trial of cell therapy to treat postradical prostatectomy erectile dysfunction (INSTIN, INtra-cavernous STem-cell INjection clinical trial, NCT01089387). In this first stage, four doses of intracavernous autologous bone marrow mononuclear cells (BM-MNCs) were tested in 12 patients. Here, we report the results of stage II, in which six additional patients received the optimal dose identified in stage I (10⁹ BM-MNCs), and the long-term results in the 12 patients included in stage I. The objectives were to assess the safety and efficacy of this new treatment. In stage II, no patients had side effects, and the erectile function improvements were similar to those seen in stage I: after 6 months, significant improvements versus baseline were noted in International Index of Erectile Function-15 intercourse satisfaction (7.8 ± 3.1 vs 2.2 ± 3.4, p = 0.033) and erectile function (18 ± 8.3 vs 3.7 ± 4.1, p = 0.035) domains. In stage I patients, after a mean follow-up of 62.1 ± 11.7 mo, there were no prostate cancer recurrences, and erectile function scores were somewhat lower compared with the 1-yr time point. These findings suggest that intracavernous BM-MNC injections are safe and improve erectile function. The decline in erectile function over time suggests a need for assessing repeated injections.
Patient summary
We report a phase 1/2 pilot clinical trial of cell therapy consisting in intracavernous injection of bone marrow mononuclear cells to treat postradical prostatectomy erectile dysfunction. Erectile function was improved after 6 mo in the patients given 1 × 10⁹ cells. No serious side effects (life threatening or requiring hospitalisation) occurred after a mean follow-up of 62.1 mo in the first 12 patients.
Unlabelled:
Evidence from animal models replicating postradical prostatectomy erectile dysfunction (pRP-ED) suggests intracavernous injection of bone marrow-mononuclear cells (BM-MNCs) as a promising treatment approach for pRP-ED. We conducted a phase 1/2 pilot clinical trial of intracavernous autologous BM-MNC injection to treat pRP-ED (NCT01089387). Twelve patients with localized prostate cancer and vasculogenic pRP-ED refractory to maximal medical treatment were divided into four equal groups treated with escalating BM-MNC doses (2×10(7), 2×10(8), 1×10(9), 2×10(9)). Tolerance was the primary endpoint. Secondary endpoints were the effects on erectile function and penile vascularization at 6 mo, as assessed using the International Index of Erectile Function-15 and Erection Hardness Scale questionnaires, and color duplex Doppler ultrasound. We measured the peak systolic velocity in cavernous arteries and assessed endothelial function using the penile nitric oxide release test. No serious side effects occurred. At 6 mo versus baseline, significant improvements of intercourse satisfaction (6.8±3.6, 3.9±2.5, p=0.044) and erectile function (17.4±8.9, 7.3±4.5, p=0.006) domains of the International Index of Erectile Function-15 and Erection Hardness Scale (2.6±1.1, 1.3±0.8, p=0.008) were observed in the total population. Spontaneous erections showed significantly greater improvement with the higher doses. Clinical benefits were associated with improvement of peak systolic velocity and of % penile nitric oxide release test and sustained after 1 yr. Our results need to be confirmed by phase 2 clinical trials.
Patient summary:
We report a phase 1/2 pilot clinical trial investigating cell therapy with injection of bone marrow mononucleated cells to treat postradical prostatectomy erectile dysfunction. No serious side effects occurred. Improvements of erectile function and penile vascularization were noted. Further studies are required to confirm these preliminary results.
IntroductionErectile dysfunction (ED) affects quality of life in patients treated by radical prostatectomy (RP). The Erection Hardness Score (EHS) is a single-item scale that has demonstrated good psychometric properties for assessing erectile function (EF) in patients treated by sildenafil, but its applicability to other treatment contexts has not yet been tested.AimThis study aims to test the validity and time and treatment responsiveness of the EHS to assess ED in men with post-RP ED treated with alprostadil injections.Methods
This is a 1-year follow-up cohort study of 75 patients treated by RP for localized prostate cancer in a urology department setting between January 2007 and December 2008. Data were prospectively collected at 6 and 12 months post-RP.Main Outcome MeasuresThe EHS, the International Index of Erectile Function (IIEF) reference questionnaire, the Global Assessment Questionnaire (GAQ), and Numeric Pain Scale (NPS) were collected. Convergent validity (Spearman correlation coefficients with IIEF domains), known-groups validity (comparing EHS scores across ED severity groups), time and treatment responsiveness (effect size with/without treatment and over the follow-up period), and predictive ability (area under the receiver operating characteristics curve [AUC-ROC]) were analyzed for this study.ResultsThe EHS showed good convergent validity (all Spearman coefficients significant at the P < 0.05 level), adequate known-groups validity (global differentiation between IIEF-EF severity groups; P < 0.001), and treatment responsiveness (effect size: +1.8 [6 months], +2.1 [12 months]), but limited time responsiveness and predictive ability of the EHS for a normal EF at 12 months follow-up when compared with the IIEF-EF domain (AUC-ROC: 0.72 vs. 0.85; P < 0.01).Conclusion
Our findings support the overall good psychometric properties of the EHS in patients with post-RP ED treated with alprostadil injections. However, evidence for limited predictive validity and responsiveness to change over time should be considered for its use in clinical follow-up in this population. Parisot J, Yiou R, Salomon L, de la Taille A, Lingombet O, and Audureau E. Erection hardness score for the evaluation of erectile dysfunction: Further psychometric assessment in patients treated by intracavernous prostaglandins injections after radical prostatectomy. J Sex Med **;**:**–**.
Erectile dysfunction (ED) is the most commonly studied sexual disorder. ED is defined by a consistent or recurrent inability to attain and/or maintain penile erection sufficient for sexual activity.
Medical literature was reviewed and combined with expert opinion of the authors.
A review of ED prevalence is less than 10% in men aged below 50, superior to 20% for men over 60. Age, cardiovascular diseases, diabetes, hypercholesterolemia, smoking, depression and psychiatric illness, psychological disorders, unfavorable socio-economic conditions are all risk factors for erectile dysfunction. Drug sexual side-effects must also be envisaged. Erectile dysfunction can be psychogenic, organic or a mix of both. The pathophysiological mechanisms are diverse and can implicate deterioration of the central or peripheral neural pathways, from the arterial supply to the penis, endothelial dysfunction, smooth muscle tone impairment, structural damage of the sinusoidal spaces of the erectile tissue, or even hormonal disorders. Psychological and sexological management can help some patients suffering from psychogenic erectile dysfunction, usually associated with pharmacological treatment. Phosphodiesterase type 5 inhibitors (PDE5i) on demand or daily are an efficient symptomatic treatment in two thirds of patients with all forms of erectile dysfunction. Diabetic patients, after radical prostatectomy and/or with severe cardiovascular diseases respond poorly to PDE5i. Intracavernous injections of PGE1 or vacuum pump provide second line treatment for most patients. Penile implants are third line treatment and when the indication is carefully established give excellent results.
ED work-up and treatment are highly standardized. Therapeutic success rates are high.
Intracavernous injection of cultured adipose-derived stem cells (ADSCs) effectively restores erectile function in cavernous nerve (CN)-injured rats when administered at the time of injury. However, culturing exposes ADSCs to the risk of contamination and dedifferentiation.
Explore the effect of uncultured autologous adipose-derived stromal vascular fraction (SVF) on improving erectile function in a rat model of CN injury when administered at the time of injury or 4 wk after injury.
Eighty-nine male Sprague Dawley rats were randomly divided into four groups. CN injury or sham surgery was performed at the start of the study, and rats were treated with either SVF or vehicle. Functional testing and histologic analysis were performed 12 wk after CN crush or sham surgery.
We used intracavernous injection of saline immediately after CN crush (n=23), intracavernous injection of SVF immediately after CN crush (n=17), intracavernous injection of SVF 4 wk after CN crush (n=23), or sham surgery (n=26). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied intracavernous pressure (ICP) response to CN electrostimulation and performed histologic examination of midpenile cross-sections. Data were analyzed using one-way analysis of variance followed by the Tukey-Kramer test.
Both immediate and delayed treatment with SVF resulted in a significantly increased ICP-to-mean arterial pressure ratio compared with the vehicle-treated group. Both immediate and delayed treatment with SVF significantly increased expression of neuronal nitric oxide synthase and neurofilament in dorsal penile nerves compared to the vehicle group. Furthermore, the smooth muscle-to-collagen ratio within the corpus cavernosum was significantly improved in both of the SVF groups compared to vehicle-treated rats. The main limitation of the study is the lack of determination of the SVF components.
Uncultured autologous SVF injected immediately or 4 wk after CN crush improved erectile function, promoted nerve regeneration, and prevented fibrosis of the corpus cavernosum following CN injury.
Despite widespread adoption of the six-item erectile function (EF) domain of the International Index of Erectile Function (IIEF) as a clinical trial end point, there are currently no objective data on what constitutes a minimal clinically important difference (MCID) in the EF domain.
Estimate the MCID for the IIEF EF domain.
Anchor-based MCIDs were estimated using data from 17 randomized, double-blind, placebo-controlled, parallel-group clinical trials of the phosphodiesterase type 5 inhibitor (PDE5-I) tadalafil for 3345 patients treated for 12 wk.
The anchor for the MCID is the minimal improvement measure calculated using change from baseline to 12 wk on IIEF question 7: "Over the past 4 weeks, when you attempted sexual intercourse how often was it satisfactory for you?" MCIDs were developed using analysis of variance (ANOVA)- and receiver operating characteristic (ROC)-based methods in a subset of studies (n=11) by comparing patients with and without minimal improvement (n=863). MCIDs were validated in the remaining six studies (n=377).
The ROC-based MCID for the EF domain was 4, with estimated sensitivity and specificity of 0.74 and 0.73, respectively. MCIDs varied significantly (p<0.0001) according to baseline ED severity (mild: 2; moderate: 5; severe: 7). MCIDs consistently distinguished between patients in the validation sample classified as no change or minimally improved overall and by geographic region, ED etiology, and age group. MCIDs did not differ by age group, geographic region, or ED etiology. Current analyses were based on 17 clinical trials of tadalafil. Results need to be replicated in studies using other PDE5-Is or in nonpharmacologic intervention studies.
The contextualization of treatment-related changes in terms of clinically relevant improvement is essential to understanding treatment efficacy, to interpreting results across studies, and to managing patients effectively. This analysis provides, for the first time, anchor-based estimates of MCIDs in the EF domain score of the IIEF.
Intracavernous (IC) injection of stem cells has been shown to ameliorate cavernous-nerve (CN) injury-induced erectile dysfunction (ED). However, the mechanisms of action of adipose-derived stem cells (ADSC) remain unclear.
To investigate the mechanism of action and fate of IC injected ADSC in a rat model of CN crush injury.
Sprague-Dawley rats (n=110) were randomly divided into five groups. Thirty-five rats underwent sham surgery and IC injection of ADSC (n=25) or vehicle (n=10). Another 75 rats underwent bilateral CN crush injury and were treated with vehicle or ADSC injected either IC or in the dorsal penile perineural space. At 1, 3, 7 (n=5), and 28 d (n=10) postsurgery, penile tissues and major pelvic ganglia (MPG) were harvested for histology. ADSC were labeled with 5-ethynyl-2-deoxyuridine (EdU) before treatment. Rats in the 28-d groups were examined for erectile function prior to tissue harvest.
IC pressure recording on CN electrostimulation, immunohistochemistry of the penis and the MPG, and number of EdU-positive (EdU+) cells in the injection site and the MPG.
IC, but not perineural, injection of ADSC resulted in significantly improved erectile function. Significantly more EdU+ ADSC appeared in the MPG of animals with CN injury and IC injection of ADSC compared with those injected perineurally and those in the sham group. One day after crush injury, stromal cell-derived factor-1 (SDF-1) was upregulated in the MPG, providing an incentive for ADSC recruitment toward the MPG. Neuroregeneration was observed in the group that underwent IC injection of ADSC, and IC ADSC treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum.
CN injury upregulates SDF-1 expression in the MPG and thereby attracts intracavernously injected ADSC. At the MPG, ADSC exert neuroregenerative effects on the cell bodies of injured nerves, resulting in enhanced erectile response.
Plasma rich in growth factors (PRGF-Endoret) is an endogenous therapeutic technology that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing and bone regeneration. This autologous biotechnology is designed for the in situ delivery of multiple cellular modulators and the formation of a fibrin scaffold, thereby providing different formulations that can be widely used in numerous medical and scientific fields including dentistry, oral implantology, orthopedics, ulcer treatment and tissue engineering among others. Here we discuss the important progress that has been accomplished in this field. Furthermore, a comprehensive outlook of the intriguing therapeutic applications of this technology is presented.
Platelet-rich plasma (PRP) promotes regeneration of bone, presumably through the action of concentrated growth factors. However, it is not clear how PRP affects the inflammatory response. The purpose of this study was to analyze the growth factors in PRP and to study the effects of PRP on monocyte cytokine release and lipoxin A(4) (LXA(4)) generation.
PRP was prepared from healthy donors. Platelet-derived growth factor (PDGF)-AB, PDGF-BB, transforming growth factor-beta1, insulin-like growth factor-I, fibroblast growth factor-basic (FGF-b), epidermal growth factor (EGF), vascular endothelial growth factor, interleukin-12 (p40/70), and regulated on activation, normal T-cell expressed and secreted (RANTES) levels were evaluated by enzyme-linked immunosorbent assay and bead-based multiplexing. Peripheral blood monocytes were isolated and cultured with or without PRP. Cytokine, chemokine, and LXA(4) levels as well as monocyte chemotactic migration were analyzed.
Growth factors were increased significantly in PRP compared to whole blood (WB) and platelet-poor plasma. Monocyte chemotactic protein-1 (MCP-1) was suppressed significantly by PRP, whereas RANTES was increased significantly in monocyte cultures. LXA(4) levels were significantly higher in PRP compared to WB. PRP stimulated monocyte chemotaxis in a dose-dependent fashion, whereas RANTES, in part, was responsible for PRP-mediated monocyte migration.
PRP is a rich source of growth factors and promoted significant changes in monocyte-mediated proinflammatory cytokine/chemokine release. LXA(4) was increased in PRP, suggesting that PRP may suppress cytokine release, limit inflammation, and, thereby, promote tissue regeneration.
Significant scientific advances during the past 3 decades have deepened our understanding of the physiology and pathophysiology of penile erection. A critical evaluation of the current state of knowledge is essential to provide perspective for future research and development of new therapies.
To develop an evidence-based, state-of-the-art consensus report on the anatomy, physiology, and pathophysiology of erectile dysfunction (ED).
Consensus process over a period of 16 months, representing the opinions of 12 experts from seven countries.
Expert opinion was based on the grading of scientific and evidence-based medical literature, internal committee discussion, public presentation, and debate.
ED occurs from multifaceted, complex mechanisms that can involve disruptions in neural, vascular, and hormonal signaling. Research on central neural regulation of penile erection is progressing rapidly with the identification of key neurotransmitters and the association of neural structures with both spinal and supraspinal pathways that regulate sexual function. In parallel to advances in cardiovascular physiology, the most extensive efforts in the physiology of penile erection have focused on elucidating mechanisms that regulate the functions of the endothelium and vascular smooth muscle of the corpus cavernosum. Major health concerns such as atherosclerosis, hyperlipidemia, hypertension, diabetes, and metabolic syndrome (MetS) have become well integrated into the investigation of ED.
Despite the efficacy of current therapies, they remain insufficient to address growing patient populations, such as those with diabetes and MetS. In addition, increasing awareness of the adverse side effects of commonly prescribed medications on sexual function provides a rationale for developing new treatment strategies that minimize the likelihood of causing sexual dysfunction. Many basic questions with regard to erectile function remain unanswered and further laboratory and clinical studies are necessary.
Platelet-rich plasma is defined as autologous blood with a concentration of platelets above baseline values. Platelet-rich plasma has been used in maxillofacial and plastic surgery since the 1990s; its use in sports medicine is growing given its potential to enhance muscle and tendon healing. In vitro studies suggest that growth factors released by platelets recruit reparative cells and may augment soft-tissue repair. Although minimal clinical evidence is currently available, the use of platelet-rich plasma has increased, given its safety as well as the availability of new devices for outpatient preparation and delivery. Its use in surgery to augment rotator cuff and Achilles tendon repair has also been reported. As the marketing of platelet-rich plasma increases, orthopaedic surgeons must be informed regarding the available preparation devices and their differences. Many controlled clinical trials are under way, but clinical use should be approached cautiously until high-level clinical evidence supporting platelet-rich plasma efficacy is available.
The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on cavernous nerve (CN) regeneration and functional status in a nerve-crush rat model. Twenty-four Sprague-Dawley male rats were randomly divided into three equal groups: eight had a sham operation, eight underwent bilateral nerve crushing with no further intervention and eight underwent bilateral nerve crushing with an immediate application of PRP on the site of injury. Erectile function was assessed by CN electrostimulation at 3 months and nerve regeneration was assessed by toluidine blue staining of CN and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. Three months after surgery, in the group that underwent bilateral nerve crushing with no further intervention, the functional evaluation showed a lower mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure (MAP) with CN stimulation than those in the sham group. In the group with an immediate application of PRP, the mean maximal ICP and maximal ICP/MAP were significantly higher than those in the injured control group. Histologically, the group with the application of PRP had more myelinated axons of CNs and more NADPH-diaphorase-positive nerve fibres than the injured control group but fewer than the sham group. These results show that the application of PRP to the site of CN-crush injury facilitates nerve regeneration and recovery of erectile function. Our research indicates that clinical application of PRP has potential repairing effect on CN and peripheral nerves.
To investigate the pathophysiology of postprostatectomy erectile dysfunction (pPED) in a rat model of bilateral cavernous nerve ablation (BCNA) and to assess the effects of local bone marrow mononuclear cell (BMMNC) injection on erectile dysfunction (ED) and cavernosal cellular abnormalities caused by BCNA.
This was an experimental study in Fisher rats with BCNA.
Intervention included BNCA, electrical stimulation of the pelvic ganglion, and local BMMNC injection.
Erectile responses to electric pelvic ganglion stimulation were studied. Cavernous tissue was examined to determine the cell types undergoing apoptosis and to detect changes in protein and gene expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) using real-time quantitative polymerase chain reaction (RTQ-PCR) and Western blotting. The effects of local BMMNC injection on these parameters were studied.
Diffuse apoptosis was noted in the connective tissue mesenchymal cells and vascular smooth muscle and endothelial cells. Compared with sham-operated controls, nNOS and eNOS levels were decreased after 3 wk and were normal (eNOS) or increased (nNOS) after 5 wk, suggesting spontaneous nerve regeneration. Despite nNOS recovery, erectile responses to electrical stimulation remained impaired after 5 wk, when mesenchymal cell apoptosis was the main persistent biologic abnormality. BMMNC injection decreased apoptotic cell numbers, accelerated the normalisation of nNOS and eNOS, and partially restored erectile responses at week 5.
Massive cell apoptosis may play a key role in the pathophysiology of pPED. In this animal model, apoptosis persisted despite spontaneous nerve regeneration, suggesting that the course of BCNA-induced cell dysfunction was independent of reinnervation. BMMNC improved erectile function by inhibiting apoptosis and may hold promise for repairing penile cell damage caused by radical prostatectomy (RP).
To develop a brief, reliable, self-administered measure of erectile function that is cross-culturally valid and psychometrically sound, with the sensitivity and specificity for detecting treatment-related changes in patients with erectile dysfunction.
Relevant domains of sexual function across various cultures were identified via a literature search of existing questionnaires and interviews of male patients with erectile dysfunction and of their partners. An initial questionnaire was administered to patients with erectile dysfunction, with results reviewed by an international panel of experts. Following linguistic validation in 10 languages, the final 15-item questionnaire, the international index of Erectile Function (IIEF), was examined for sensitivity, specificity, reliability (internal consistency and test-retest repeatability), and construct (concurrent, convergent, and discriminant) validity.
A principal components analysis identified five factors (that is, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) with eigenvalues greater than 1.0. A high degree of internal consistency was observed for each of the five domains and for the total scale (Cronbach's alpha values of 0.73 and higher and 0.91 and higher, respectively) in the populations studied. Test-retest repeatability correlation coefficients for the five domain scores were highly significant. The IIEF demonstrated adequate construct validity, and all five domains showed a high degree of sensitivity and specificity to the effects of treatment. Significant (P values = 0.0001) changes between baseline and post-treatment scores were observed across all five domains in the treatment responder cohort, but not in the treatment nonresponder cohort.
The IIEF addresses the relevant domains of male sexual function (that is, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), is psychometrically sound, and has been linguistically validated in 10 languages. This questionnaire is readily self-administered in research or clinical settings. The IIEF demonstrates the sensitivity and specificity for detecting treatment-related changes in patients with erectile dysfunction.
We aimed to determine whether erectile function (EF) and assessments of erection hardness correlate positively with measures of psychosocial outcomes (ie, emotional well-being, sexual satisfaction, and satisfaction with erectile dysfunction [ED] treatment) in men treated with sildenafil citrate (Viagra; Pfizer Inc, New York, NY). Data were collected from 33 worldwide phase 2, 3, and 4 sildenafil clinical trials, which included almost 10,000 men with ED. Most of these trials were randomized, double-blind, and placebo-controlled (n = 27) and were undertaken to assess doses of 50 mg adjustable to 25 mg or 100 mg, depending on efficacy and tolerability (n = 32). Doses were taken approximately 1 hour before anticipated sexual activity but not more often than once daily. EF was assessed with use of the EF domain of the International Index of Erectile Function (IIEF) and with assessments of erection hardness (Erection Hardness Grading Scale [EHGS] and IIEF Q2 [the frequency of erections hard enough for penetration]). Change (baseline to end point) in emotional well-being in men treated for ED was assessed with the Self-Esteem and Relationship (SEAR) questionnaire, which consisted of the Confidence domain (ie, the Self-Esteem subscale and Overall Relationship subscale) and the Sexual Relationship domain. End point treatment satisfaction (overall, speed of onset, and duration of action) was assessed with the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). The IIEF was used to assess change and end point sexual satisfaction by means of the Intercourse Satisfaction domain, Q7 (frequency of satisfactory sexual intercourse), and the Overall Satisfaction domain (ie, Q13, satisfaction with sex life, and Q14, satisfaction with sexual relationship). In men treated with sildenafil for ED, scores for measures of EF (IIEF EF domain, IIEF Q2) and the percentage of erections graded completely hard and fully rigid (EHGS grade 4) correlated positively with scores for measures of psychosocial outcomes (SEAR emotional well-being, IIEF sexual satisfaction, and EDITS ED treatment satisfaction), indicating that when EF improved and erection hardness increased, these measures of psychosocial function also improved.
Platelet activation and subsequent release of granules containing a variety of growth factors, at the site of injury, is crucial for the wound healing process. We postulated that a platelet-mediated paracrine effect may accelerate the healing process after myocardial infarction.
Allogenic platelet-rich and platelet-poor plasma (PRP and PPP) were collected from 15 healthy male Wistar rats. After thrombin activation, the level of vascular endothelial growth factor (VEGF) in PRP and PPP was measured by enzyme-linked immunosorbent assay. A rat model of myocardial infarction was induced by permanent ligation of the left anterior descending artery, and thrombin-activated PRP and PPP, respectively, were injected into the ischemic region. Seven days and 28 days after operation, surviving rats were killed. Ex-vivo left ventricular pressure-volume relationship was performed to evaluate passive diastolic function. Collagen analysis was performed by picrosirius red staining plus polarized microscopy. Angiogenesis and arteriogenesis were evaluated by immunofluorescent staining.
After thrombin activation, VEGF level in PRP was significantly higher than that in PPP (187.5+/-45.5 vs. 30.1+/-7.8 pg/ml, P<0.01). Injection of thrombin-activated PRP into the infarcted area resulted in improvement of ventricular remodeling and accelerated healing, as demonstrated by limitation of ventricular expansion, attenuation of myocardial hypertrophy in the noninfarct region, facilitation of angiogenesis and arteriogenesis in the infarct.
Injection of thrombin-activated PRP could modulate favorably the postinfarction remodeling process. Platelet-released VEGF may participate in this protective effect.
Biotherapies for erectile dysfunction and Peyronie's disease: Where are we now?
- Akakpo
Men's health: sexual dysfunction, physical, and psychological health-is there a link?
- H M Tan
- S F Tong
- Cck Ho
Tan HM, Tong SF, Ho CCK. Men's health: sexual dysfunction,
physical, and psychological health-is there a link? J Sex Med
2012;9(3):663-71.
Apoptosis and effects of intracavernous bone marrow cell +Model PUROL-2368
- P A Fall
- M Izikki
- L Tu
- S Swieb
- F Giuliano
- J Bernabe
Fall PA, Izikki M, Tu L, Swieb S, Giuliano F, Bernabe J, et al.
Apoptosis and effects of intracavernous bone marrow cell
+Model
PUROL-2368; No. of Pages 6
Biotherapies for erectile dysfunction and Peyronie's disease: Where are we now?
- W Akakpo
- A Schirmann
- L Ferretti
- K Ben-Naoum
- D Carnicelli
- J-P Graziana
Akakpo W, Schirmann A, Ferretti L, Ben-Naoum K, Carnicelli
D, Graziana J-P, et al. Biotherapies for erectile dysfunction and Peyronie's disease: Where are we now? Prog Urol
2020;30(16):1000-13.