Platelet-rich Plasma for the Treatment of Erectile Dysfunction: A Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial

You have accessJournal of UrologyAdult Urology30 Apr 2023Platelet-rich Plasma for the Treatment of Erectile Dysfunction: A Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial Thomas A. Masterson, Manuel Molina, Braian Ledesma, Isaac Zucker, Russell Saltzman, Emad Ibrahim, Sunwoo Han, Isildinha M. Reis, and Ranjith Ramasamy Thomas A. MastersonThomas A. Masterson *Correspondence: Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, 1120 NW 14th St, Suite 1563, Miami, FL 33136 telephone: 305-243-4562; E-mail Address: [email protected] https://orcid.org/0000-0001-5211-9271 Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida , Manuel MolinaManuel Molina Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida , Braian LedesmaBraian Ledesma Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida , Isaac ZuckerIsaac Zucker Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida , Russell SaltzmanRussell Saltzman Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida , Emad IbrahimEmad Ibrahim Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida , Sunwoo HanSunwoo Han Biostatistics and Bioinformatics Shared Resources, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida , Isildinha M. ReisIsildinha M. Reis Biostatistics and Bioinformatics Shared Resources, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida , and Ranjith RamasamyRanjith Ramasamy Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida View All Author Informationhttps://doi.org/10.1097/JU.0000000000003481AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Abstract Purpose: We assessed the safety and efficacy of 2 injections of platelet-rich plasma for treating mild to moderate erectile dysfunction by conducting a prospective, randomized, double-blind, placebo-controlled clinical trial. Materials and Methods: Men with mild to moderate erectile dysfunction (International Index of Erectile Function scores 11-25) were randomized to receive either 2 injections of platelet-rich plasma or placebo separated by 1 month. Primary outcome was percentage of men meeting minimum clinically important difference at 1 month after the second injection. Secondary outcomes were change in International Index of Erectile Function at 1, 3, and 6 months, and changes in penile vascular parameters and adverse events at 6 months. Results: We randomized 61 men: 28 into platelet-rich plasma and 33 into placebo. There was no difference between groups in percentage of men meeting minimum clinically important difference at 1 month: 14 (58.3%) in platelet-rich plasma vs 15 (53.6%) in placebo (P = .730). Mean International Index of Erectile Function–Erectile Function domain changed from 17.4 (95% CI 15.8-19.0) to 21 (17.9-24.0) at 1 month in men receiving platelet-rich plasma, vs 18.6 (17.3-19.8) to 21.6 (19.1-24.1) in the placebo group; however, there was no significant difference between groups (P = .756). There were no major adverse events and only 1 minor adverse event in each group. There were no changes in penile Doppler parameters from baseline to 6 months. Conclusions: The results of our prospective, double-blind, randomized, placebo-controlled clinical trial suggest that 2 injections of intracavernosal platelet-rich plasma separated by 1 month in men with mild to moderate erectile dysfunction is safe, but we found no difference in efficacy between platelet-rich plasma and placebo. Erectile dysfunction (ED) affects as many as 1 in 4 men, and the incidence appears to be increasing.1 Guideline-supported medical treatments for ED work through transient vasodilation by way of augmentation of the nitric oxide pathway.2 While these treatments are effective for many men suffering from ED, they are incapable of reversing the underlying pathology. Furthermore, many men will discontinue medical therapies due to lack of efficacy and side effects.3,4 Therefore, there is increasing interest in restorative therapies such as shock wave therapy and platelet-rich plasma (PRP) that may be capable of reversing underlying pathology and reestablishing natural spontaneous erections. PRP is an autologous blood product created by centrifugation and separation of whole blood. The PRP layer contains 5 times the concentration of platelets as whole blood and is injected into an area of pathology.5 PRP contains growth factors, including platelet-derived growth factor, transforming growth factor β, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor, and fibroblast growth factor.6 These growth factors are involved in complex healing processes, most notably neoangiogenesis, stimulation of cellular growth, and recruitment of immune cells. These properties have made PRP an attractive treatment for orthopedic injures and sports medicine, and it is widely used for treating osteoarthritis and cartilage defect.7 Preclinical studies also suggest that these growth factors may be beneficial in ED.8-10 Despite the hypothesized mechanisms and benefits that may make PRP an attractive treatment, there is remarkably little clinical evidence supporting its use in ED. Even without supporting data, numerous clinics in the largest metropolitan areas of the Unites States are charging patients for PRP treatments for ED.11 Our objective was to assess the safety and clinical efficacy of PRP for treating mild to moderate ED through a prospective, randomized, double-blind, placebo-controlled clinical trial. We hypothesized that PRP would improve erectile function in men with mild to moderate ED as compared to placebo. METHODS Study Design This study was a prospective, randomized, double-blind, placebo-controlled clinical trial performed at the outpatient clinic of the Desai Sethi Urology Institute, Miami, Florida. The study protocol was approved by our Institutional Review Board (IRB No. 20200373) and registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT04396795). This study was performed in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement, and all participants provided written informed consent before enrollment. Patients were recruited from May 2020 to August 2022, and the results were obtained in November 2022. Selection Criteria Eligible men were between age 30 and 75 (inclusive) with organic ED, defined as International Index of Erectile Function (IIEF) score of 11-25 (inclusive) for at least 6 months, with normal testosterone levels, and hemoglobin A1c less than 9%. Men using intracavernosal injections or urethral suppositories for ED treatment were excluded from participation due to severity of ED. Men were allowed to take and continue phosphodiesterase type 5 (PDE5) inhibitors at their same dosage if they were taking them during screening and asked to report either discontinuation or increase in dosage during as well at the end of the study period. No dosage adjustments were allowed during the study period. Men with suspected psychogenic ED based on clinical history as determined by the investigators, with any planned urological surgeries during the study period, or who were deemed unfit for the trial by the principal investigator were excluded. Study Protocol Men were prescreened with a thorough history and physical exam, IIEF-Erectile Function domain (EF) and Sexual Encounter Profile-3 questionnaires, and measurement of serum testosterone using liquid chromatography tandem mass spectrometry before 10 am, hemoglobin A1c, and complete blood count. Eligible men underwent a baseline penile duplex ultrasound to measure penile vascular parameters: peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index. After signing consent, participants were sequentially randomized 1:1 to receive treatment or placebo. Randomization was performed using RedCap. Only 1 member of the study team (MM) was aware of the treatment allocations, and that researcher was not involved with data collection and outcome analysis. This study member did not have access to pre- or posttreatment data. Regardless of randomization, patients underwent 2 sessions of intracavernosal injections separated by 28±7 days. Sessions began by obtaining 120 mL autologous blood via phlebotomy of the brachial vein. The blood was processed in a separate room using the Arthrex Angel PRP system. Arthrex Angel is an automated PRP system that contains an optical sensor to separate out the platelet-rich layer.5 Approximately 5 mL PRP was extracted from 120 mL whole blood. For the treatment group, the PRP was placed into two 5-mL syringes (2.5 mL PRP in each) covered with foil to maintain blinding (Supplemental Figure 1, https://www.jurology.com). In the sham group, the PRP was saved and frozen for future laboratory studies. To prepare for injection, the patient was positioned supine, and ice was applied to the penis for 5 minutes to reduce injection site pain prior to injection. A sterile field was created on the penis. A 1/4-inch Penrose drain was placed at the base of the penis to create a tourniquet and maintained in place under tension with a sterile clamp for 20 minutes. Approximately 2.5 mL PRP (treatment) or normal saline (sham) was injected into the right and left corpus cavernosum for a total of 5 mL (regardless of the amount of PRP that was obtained from 120 mL blood). After 20 minutes, the tourniquet was removed, and the subject released from the clinic. To ensure fair enrollment in the clinical trial, we provided men who were randomized to placebo during the trial with PRP free of charge after the 6-month follow-up time point. Outcomes Primary outcome was percentage of men attaining minimum clinically important difference (MCID) at 1 month after the second injection. MCID is an increase of 2 points for mild ED (starting IIEF-EF 17-25) and 5 points for moderate ED (starting IIEF-EF 11-16).12 We continued data collection out to 6 months to assess for safety and durability. Secondary outcomes were changes in IIEF-EF scores, changes in penile vascular parameters (PSV, EDV), and adverse events. Patients were followed at 1, 3, and 6 months after the last injection to assess long-term side effects and durability of response. Scientific Rigor and Reproducibility We employed a double-blind design to reduce bias and increase the validity of the results. Neither the participants nor the investigators knew the treatment assignment of the participants. To achieve this, we had only 1 person in the study team in charge of preparing both the PRP and placebo injections, that were then packaged and labeled in an identical-looking way that the investigators and participants were not able to identify the treatment group. The allocation of participants to the treatment or control groups was done by this same person using a computer-generated randomization schedule. Additionally, we took steps to ensure that the investigator who was blinded was not involved in the outcome analysis. This was accomplished by assigning the outcome assessment to an independent third party not aware of the participants' treatment assignment. This further helped to reduce bias and increase the validity of the results. Sample Size Calculation Previous studies on the effect of placebo show about 15% attaining MCID in men with mild to moderate ED.13 In the interventional PRP group, we expected 50% of patients would meet MCID. Sample size of 27 patients in each group achieves 80% power to detect a difference of 35% between PRP and placebo, using a 2-sided Z-test with pooled variance at 5% significance level. Assuming a 10% dropout rate, we planned to recruit a total of 60 subjects. Statistical Analysis Descriptive statistics were used to summarize demographic and baseline patient characteristics, and primary and secondary outcomes. In general, 2 groups were compared using χ2 test or Fisher's exact test for categorical variables, and 2-sample t-test or Wilcoxon rank-sum test for continuous variables; paired data in each group were compared using the paired t-test or the Wilcoxon signed-rank test for continuous variables, or the McNemar's test for categorical variables. The Wilcoxon signed-rank test was used for comparison of changes in penile vascular parameter PSV from baseline to 6-month follow-up visit in each group, while the Wilcoxon rank-sum test was used for comparisons between groups. Since the majority of values for EDV were value 0, we analyzed EDV as a categorical variable (0 vs >0) using the McNemar's test to compare proportions between baseline and 6 months in each group and the χ2 test to compare 2 proportions between groups at a specific time visit. For outcome IIEF-EF score, we also performed longitudinal data analysis using a linear mixed model for assessing effects of group, time, and their interaction (group × time), using residual maximum likelihood estimation and assuming any missing data are missing at random. We assumed an unstructured covariance for the time-correlated data structure. The statistical significance was set as P < .05, and analyses were performed in SAS 9.4. RESULTS We recruited and randomized 61 men: 28 into PRP and 33 into placebo. We had complete 1-month data for 24 men receiving PRP and 28 receiving placebo. Additionally, we had complete 6-month data for 20 men receiving PRP and 24 receiving placebo (Figure 1). There were no differences in baseline demographics or characteristics between men who received treatment and those who received placebo, except that there were more men with prediabetes receiving placebo compared to PRP (8 vs 1) despite similar median A1c level (Table 1). Figure 1. Patient flow diagram. FU indicates follow-up;IIEF, International Index of Erectile Function; PRP, platelet-rich plasma. Table 1. Baseline Characteristics Characteristic PRP Placebo Total patients, No. (%) 28 (100) 33 (100) Age, median (IQR), y 49 (38.5, 55) 46 (42, 56) BMI, median (IQR), kg/m2 27.9 (24.5, 30.3) 28.5 (25.7, 31.1) BMI, No. (%), kg/m2 <25 (healthy) 8 (28.6) 4 (12.1) 25-29.9 (overweight) 13 (46.4) 16 (48.5) ≥30 (obese) 7 (25) 13 (39.4) Not current smoker, No. (%) 26 (92.9) 33 (100) CAD, No. (%) 3 (10.7) 3 (9.1) HTN, No. (%) 8 (28.6) 10 (30.3) HLD, No. (%) 7 (25) 8 (24.2) DM, No. (%) 3 (10.7) 3 (9.1) Comorbidities, No. (%)a 0 14 (50) 18 (54.5) 1 7 (25) 10 (30.3) 2+ 7 (25) 5 (15.2) Hemoglobin A1c at baseline, median (IQR) 5.4 (5.2, 5.6) 5.3 (5.1, 5.7) Hemoglobin A1c at baseline, No. (%) <5.7% (normal) 24 (85.7) 24 (72.7) 5.7-6.4% (pre-diabetes) 1 (3.6) 8 (24.2) ≥6.5% (diabetes) 3 (10.7) 1 (3) T-level, median (IQR), ng/dL 493 (388.5, 605.5) 520 (383, 699) Erectile dysfunction, No. (%) Mild (IIEF-EF scores 17-25) 16 (57.1) 21 (63.6) Moderate (IIEF-EF scores 11-16) 12 (42.9) 12 (36.4) Abbreviations: BMI, body mass index; CAD, coronary artery disease; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; IIEF-EF: International Index of Erectile Function−Erectile Function domain; PRP, platelet-rich plasma; T-level, testosterone level. There were no significant differences between the 2 groups with respect to all baseline characteristics except for hemoglobin A1c at baseline as 3 categories (P = .046). Comorbidities included CAD, DM, HLD, and HTN. For primary outcome, there was no difference between groups in percentage of men attaining MCID at 1 month: 14/24 (58.3%) in the PRP group compared to 15/28 (53.6%) in the placebo group (P = .730). For secondary outcome, mean IIEF-EF score changes from baseline to 1 month were statistically significant in both groups (mean increases of 3.7, 95% CI 0.5-6.9, P = .026 in PRP vs 3.1, 95% CI 0.8-5.4, P = .009 in placebo), but there was no statistically significant difference between groups (P = .765). Means changes from baseline to 3 months were not statistically significant in each group, and there was no difference between groups at 3 months (P = .662). However, the mean changes from baseline to 6 months were statistically significant in both groups (mean increases of 5, 95% CI 1.9-8.1, P = .003 in PRP vs 2.2, 95% CI 0.1-4.3, P = .045 in placebo), but no difference between groups (P = .116; Table 2). Table 2. Minimum Clinically Important Difference, Erectile Dysfunction, and International Index of Erectile Function−Erectile Function Domain Scores Baseline 1 Mo 3 Mo 6 Mo PRP Placebo PRP Placebo PRP Placebo PRP Placebo MCID based on IIEF-EF, No. (%) Yes NA NA 14 (58.3) 15 (53.6) 10 (41.7) 13 (52) 12 (60) 10 (41.7) No NA NA 10 (41.7) 13 (46.4) 14 (58.3) 12 (48) 8 (40) 14 (58.3) P1 NA NA NA 0.730 NA 0.469 NA 0.226 ED, No. (%) No NA NA 7 (29.2) 9 (32.1) 7 (29.2) 6 (24) 7 (35) 4 (16.7) Mild 16 (57.1) 21 (63.6) 12 (50) 13 (46.4) 8 (33.3) 15 (60) 9 (45) 15 (62.5) Moderate 12 (42.9) 12 (36.4) 3 (12.5) 4 (14.3) 4 (16.7) 2 (8) 2 (10) 5 (20.8) Severe NA NA 2 (8.3) 2 (7.1) 5 (20.8) 2 (8) 2 (10) NA P1 NA 0.605 NA 0.989 NA 0.247 NA 0.152 IIEF-EF score No. 28 33 24 28 24 25 20 24 Mean (95% CI) 17.4 (15.8, 19.0) 18.6 (17.3, 19.8) 21 (17.9, 24.0) 21.6 (19.1, 24.1) 19.2 (15.9, 22.4) 20.6 (18.1, 23.2) 22.2 (18.9, 25.4) 20.5 (18.5, 22.6) Median (IQR) 18.0 (14, 20) 18.0 (15, 22) 23.5 (17.5, 26.5) 24.0 (17.5, 27.0) 21.5 (13, 26) 21.0 (17, 25) 24.0 (18.5, 28.0) 21.0 (17, 24) Mean diff (95% CI) NA −1.2 (−3.1, 0.8) NA −0.7 (−4.5, 3.2) NA −1.4 (−5.5, 2.6) NA 1.6 (−2.0, 5.2) P2 NA 0.231 NA 0.722 NA 0.466 NA 0.376 IIEF-EF score changes from baseline No. NA NA 24 28 24 25 20 24 Mean NA NA 3.7a 3.1a 1.4 2.2 5a 2.2a 95% CI NA NA (0.5, 6.9) (0.8, 5.4) (-1.6, 4.5) (−0.2, 4.6) (1.9, 8.1) (0.1, 4.3) Median (IQR) NA (NA) NA (NA) 4.5 (0.0, 8.5) 2.0 (−0.5, 8.0) 1.0 (−3.0, 7.5) 2.0 (−1.0, 6.0) 3.5 (0.0, 9.5) 2.0 (−2.5, 7.0) Mean diff (95% CI) NA NA NA 0.6 (−3.2, 4.4) NA −0.8 (−4.6, 2.9) NA 2.8 (−0.7, 6.4) P2 NA NA NA 0.765 NA 0.662 NA 0.116 Abbreviations: CI, confidence interval; diff, difference; ED, erectile dysfunction; IIEF-EF, International Index of Erectile Function−Erectile Function domain; IQR, interquartile range; MCID, minimum clinically important difference; NA, not applicable; P1, P value from χ2 test, P2, P value from 2-sample t-test; PRP, platelet-rich plasma. MCID based on IIEF-EF score was defined as an increase of ≥2 for patients with baseline mild ED (baseline IIEF-EF score of 17-25), and ≥5 for patients with baseline moderate ED (score of 11-16). ED categories based on the IIEF-EF score: no ED (26-30), mild (17-25), moderate (11-16), and severe (0-10). Significant difference from baseline (P < .05) from paired t-test in each group. Figure 2 reports the estimated mean of IIEF-EF score obtained from a linear mixed model including group, time, and their interaction effect. The estimated mean scores were very similar to the observed mean scores in Table 2. The interaction effect (P = .832) and the group effect (P = .512) were not statistically significant, while the time effect (P = .002) was significant. Pairwise mean comparison in each group indicated significant increase in IIEF-EF scores at 1- and 6-month follow-up visits relative to baseline. Figure 2. Estimated International Index of Erectile Function–Erectile Function domain (IIEF-EF) score means with corresponding 95% confidence intervals from longitudinal data analysis. Asterisks indicate statistically significant difference between baseline and a specific follow-up time in each group (P < .05). There were no significant differences between groups at any visit (P > .05). PRP indicates platelet-rich plasma. Supplemental Table 1 (https://www.jurology.com) reports scores for IIEF intercourse and overall satisfaction domains. There was no difference between groups in both satisfaction scores at any visit time or over time compared to baseline in each group. Incidence of anticipated adverse events in all patients was recorded during the study period. There were 2 minor adverse events: 1 patient with new plaque in the PRP group and 1 patient with hematoma in the placebo group. There were no differences in adverse events between groups, and importantly, there were no major adverse events (Table 3). Table 3. Adverse Events of Platelet-rich Plasma and Placebo Injections PRP Placebo No. 28 33 Mean pain with injection 1 (score 1-10) 3.7 3.5 Mean pain with injection 2 (score 1-10) 4.1 4 Adverse events, No. (%) Major (grade 3+) 0 0 Minor (grade 1-2) 1 (3.6) 1 (3.0) Hematoma 0 1 (3.0) New plaque 1 (3.6) 0 Abbreviation: PRP, platelet-rich plasma. No patient had any of the following per-protocol anticipated adverse events: infection, swelling, or local injection site reaction such as bruising, edema, or allergy. There were no significant changes in penile Doppler parameters between baseline and 6-month visit in each group (PRP: P = .927 for PSV and P = .059 for EDV; placebo: P = .210 for PSV, P = .655 for EDV). Note, however, that there was a statistically significant difference between groups in PSV at baseline (mean 47.2 in PRP group vs 40.5 in placebo group, P = .028), but the difference was not significant at 6 months posttreatment (mean 48.8 in PRP group vs 44.7 in placebo group, P = .366). There was no significant difference between groups in EDV at baseline (proportion with EDV >0 in PRP and placebo groups, respectively, of 21.4% vs 33.3%, P = .301) or at the 6-month assessment (37.5% vs 30.8%, P = .616; Table 4). Table 4. Penile Vascular Parameters PRP Placebo Baseline 6 Mo Change Baseline 6 Mo Change PSV No. 28 24 24 33 26 26 Mean (95% CI) 47.2 (42.1, 52.4) 48.8 (42.1, 55.4) 0.4 (−7.8, 8.5) 40.5 (36.9, 44.1) 44.7 (38.3, 51.1) 4.7 (−2.8, 12.2) Median (IQR) 44.2 (36.8, 58.0) 48.8 (42.5, 56.7) 0.8 (−9.6, 15.3) 37.6 (34.5, 44.6) 43.1 (36.5, 55.8) 1.5 (−3.4, 14.8) P1 (between groups) 0.028 0.366 0.425 NA NA NA P2 (change in a group) NA NA 0.927 NA NA 0.210 EDV 0, No. (%) 22 (78.6) 15 (62.5) NA 22 (66.7) 18 (69.2) NA >0, No. (%) 6 (21.4) 9 (37.5) NA 11 (33.3) 8 (30.8) NA P1 (between groups) 0.301 0.616 NA NA NA NA P2 (change in a group) NA NA 0.059 NA NA 0.655 Abbreviations: CI, confidence interval; EDV, end diastolic velocity; IQR, interquartile range; NA, not applicable; P1(between groups), P value from 2-sample t-test for PSV and from χ2 test for EDV; P2(change in a group), P value from paired t-test for PSV and from McNemar's test for EDV; PRP, platelet-rich plasma; PSV, peak systolic velocity. DISCUSSION We set out to determine if PRP is a safe and effective treatment for men with mild to moderate ED by performing a prospective, randomized, double-blind, placebo-controlled clinical trial. Our results suggest that PRP is safe as we had almost no adverse events. Importantly, however, we found no difference in efficacy between PRP and placebo. PRP is currently marketed online as a treatment for sports injury, facial aging, hair loss, and ED. Consequently, PRP may be offered in myriad clinical settings for multiple conditions regardless of the evidence.11 This has resulted in clinics offering PRP for ED long before clinical human studies supported its use or before validated treatment protocols were established. An unfortunate consequence of PRP's rapid adoption is an extreme heterogeneity in treatment protocols, all of which are unsupported by evidence.11 Therefore, studies such as this are critical to ensuring that men with ED are receiving treatments that are both safe and effective. The first human study of PRP for the treatment of ED in the United States was published by Matz et al in 2018. They assessed the safety of PRP in 17 patients with different urological complaints, including 5 with ED. While not powered to detect any changes in IIEF, their study found that none of the subjects reported worsening ED or adverse event.14 Since this observational study, there have been 2 additional clinical trials assessing the safety and efficacy of PRP in ED, both published in 2021. The first was a case series including 31 men with ED associated with metabolic syndrome by Tas et al.15 They assessed 3 injections of 3.0 mL intracavernosal PRP, administered at intervals of 15 days. At 6-month follow-up, 19 (61%) had improved IIEF-EF scores suggesting potential efficacy. Poulios et al published their double-blind, randomized, placebo-controlled clinical trial in Greece that included 60 men with mild to moderate ED randomized to either 2 intracavernosal injections of 10 mL PRP or 10 mL normal saline separated by 1 month.16 They found that 22/29 (76%) reached IIEF MCID in the PRP group, compared to only 7/28 (25%) in the placebo group at 6 months. Both studies reported only minor, and very few, adverse events. Based on these earlier studies, we were surprised to find that PRP was no different than placebo in our study. It is possible that differences in patient population and trial design led to these differences. For example, men in our trial were able to continue PDE5 inhibitors without dose modification throughout the trial to mimic real-world experience, whereas in the other trials, men had to discontinue PDE5 use. Additionally, we used a smaller volume of PRP, 5 mL × 2 treatments in our study, vs 6 mL × 3 treatments vs 10 mL × 2 treatments. To our knowledge, this is the first prospective, randomized, double-blind, placebo-controlled clinical trial conducted in the United States assessing the safety and efficacy of PRP for ED. We are also the first to utilize the Arthrex Angel centrifuge system, with its optical sensor, to create a more concentrated and less variable PRP product. Despite the strengths of our study, there are notable limitations. The first is the short duration of follow-up (6 months), which may be inadequate to assess long-term differences. We also had a dropout rate of nearly 15% for 1-month follow-up in a relatively small study, which may affect outcome data. Additionally, the protocol we utilized was based on prior PRP studies, and it is possible that our protocol of 2 injections, 1 month apart, will not yield optimal results. It is possible that more injections or a different interval between injections may yield greater changes in IIEF-EF. More research into patient selection, protocol optimization, and PRP dosing is needed. CONCLUSIONS The results of our clinical trial suggest that 2 injections of intracavernosal PRP separated by 1 month in men with mild to moderate ED is safe, but no more effective than a placebo. More research is needed into patient selection and treatment protocol to assess efficacy. REFERENCES 1. . Measurement of erectile dysfunction in population-based studies: the use of a single question self-assessment in the Massachusetts Male Aging Study. Int J Impot Res.2000; 12(4):197-204. Crossref, Medline, Google Scholar 2. . Erectile dysfunction: AUA guideline. J Urol.2018; 200(3):633-641. Link, Google Scholar 3. . Reasons and predictive factors for discontinuation of PDE-5 inhibitors despite successful intercourse in erectile dysfunction patients. Int J Impot Res.2014; 26(3):87-93. Crossref, Medline, Google Scholar 4. . Dropout in the treatment of erectile dysfunction with PDE5: a study on predictors and a qualitative analysis of reasons for discontinuation. J Sex Med.2012; 9(9):2361-2369. Crossref, Medline, Google Scholar 5. . Cellular components and growth factor content of platelet-rich plasma with a customizable commercial system. Am J Sports Med.2019; 47(5):1216-1222. Crossref, Medline, Google Scholar 6. . Platelet rich plasma: a short overview of certain bioactive components. Open Med.2016; 11(1):242-247. Crossref, Google Scholar 7. . Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review. Osteoarthritis Cartilage.2013; 21(11):1627-1637. Crossref, Medline, Google Scholar 8. . Neuroprotective and nerve regenerative approaches for treatment of erectile dysfunction after cavernous nerve injury. Int J Mol Sci.2017; 18(8):1794. Crossref, Medline, Google Scholar 9. . The effect of platelet-rich plasma on cavernous nerve regeneration in a rat model. Asian J Androl.2009; 11(2):215-221. Crossref, Medline, Google Scholar 10. . The neuroprotective effect of platelet-rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med.2012; 9(11):2838-2848. Crossref, Medline, Google Scholar 11. . Analysis of direct-to-consumer marketing of platelet-rich plasma for erectile dysfunction in the US. JAMA Netw Open.2022; 5(5):e2214187. Crossref, Medline, Google Scholar 12. . Minimal clinically important differences in the erectile function domain of the International Index of Erectile Function scale. Eur Urol.2011; 60(5):1010-1016. Crossref, Medline, Google Scholar 13. . A randomized, double-blind, placebo-controlled, parallel study to assess the efficacy and safety of once-a-day tadalafil in men with erectile dysfunction who are naive to PDE5 inhibitors. J Sex Med.2011; 8(9):2617-2624. Crossref, Medline, Google Scholar 14. . Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions. Investig Clin Urol.2018; 59(1):61-65. Crossref, Medline, Google Scholar 15. . Early clinical results of the tolerability, safety, and efficacy of autologous platelet-rich plasma administration in erectile dysfunction. Sex Med.2021; 9(2):100313. Crossref, Medline, Google Scholar 16. . Platelet-rich plasma (PRP) improves erectile function: a double-blind, randomized, placebo-controlled clinical trial. J Sex Med.2021; 18(5):926-935. Crossref, Medline, Google Scholar Submitted January 30, 2023; accepted April 7, 2023; published 000. Support: This work was supported by NIH Grant R01 DK130991 to RR. Conflict of Interest: The Authors have no conflicts of interest to disclose. Ethics Statement: This study received Institutional Review Board approval (IRB No. 20200373). Author Contributions: Research design: TM, RR, RS; Research performance: TM, MM, BL, IZ, EI; Data analysis: SH, IR; Manuscript composition: TM, BL, RR. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Supplementary Materials Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.Keywordsclinical trialerectile dysfunctionplatelet-rich plasmaMetricsAuthor Information Thomas A. Masterson Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida *Correspondence: Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, 1120 NW 14th St, Suite 1563, Miami, FL 33136 telephone: 305-243-4562; E-mail Address: [email protected] More articles by this author Manuel Molina Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida More articles by this author Braian Ledesma Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida More articles by this author Isaac Zucker Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida More articles by this author Russell Saltzman Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida More articles by this author Emad Ibrahim Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida More articles by this author Sunwoo Han Biostatistics and Bioinformatics Shared Resources, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida More articles by this author Isildinha M. Reis Biostatistics and Bioinformatics Shared Resources, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida More articles by this author Ranjith Ramasamy Desai Sethi Urology Institute, Miller School of Medicine, University of Miami, Miami, Florida More articles by this author Expand All Submitted January 30, 2023; accepted April 7, 2023; published 000. Support: This work was supported by NIH Grant R01 DK130991 to RR. Conflict of Interest: The Authors have no conflicts of interest to disclose. Ethics Statement: This study received Institutional Review Board approval (IRB No. 20200373). Author Contributions: Research design: TM, RR, RS; Research performance: TM, MM, BL, IZ, EI; Data analysis: SH, IR; Manuscript composition: TM, BL, RR. Advertisement Advertisement PDF downloadLoading ...