madman
Super Moderator
ABSTRACT
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 the final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated.
Results: At 6 months, an 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 were 3.9 points (95%CI: 1.8-5.9). Similarly, a statistically significant difference in both the number of participants attaining an 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 the 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.
INTRODUCTION
Vasculogenic erectile dysfunction (ED) is a complex, multidimensional disorder that predominantly manifests due to reduced penile blood flow, arterial insufficiency or stenosis, as well as endothelial dysfunction.1 Most recommended treatments improve erectile function by enhancing penile hemodynamics without reversing the pathophysiologic mechanisms leading to ED.2
Platelet-rich plasma (PRP) is an autologous plasma fraction produced from the centrifugation of whole blood that contains a 3- to 7-times higher mean platelet concentration compared to whole blood.3 Due to the beneficial properties of growth factors contained in high concentrations in this fraction, numerous medical specialties have included PRP injections in the quiver of their offered treatment options.4−9 Recently, PRP intracavernosal injections emerged as a promising, angiogenic, vasculogenic and regenerative treatment modality for ED.10 Animal studies postulate that PRP injections may improve key elements of the pathophysiologic mechanisms leading to ED through antiinflammatory, reparative, neuroprotective and neurotrophic effects.11−14 Still, these mechanisms are yet neither adequately explored nor completely understood.
Despite the favorable outcomes of PRP and the exploding interest in regenerative medicine, limited data support its use as part of the established ED therapeutic algorithm.15−17 Given the paucity of human clinical trials, there is currently an unmet need for high-quality studies exploring the use of PRP for the management of ED.18 In this scope, we conducted the first double-blind, randomized, placebo-controlled clinical trial aiming to assess the efficacy and safety of PRP injections versus placebo in patients with non-severe ED.
DISCUSSION
Our findings demonstrate that intracavernosal injections with PRP is a safe and effective treatment modality for the management of non-severe ED. Based on our results, two sessions of PRP led to a statistically significant improvement of the erectile function compared to placebo and this effect was maintained for 6 months. More than two-thirds of participants in the active arm presented an MCID in the IIEF-EF scale at all follow-up evaluations, demonstrating that the improvement in erectile function may be clinically important. Furthermore, no major or minor adverse events occurred during the treatment and follow-up period. Of note, subjects receiving PRP displayed higher satisfaction rates compared to placebo, while subjects receiving placebo injections reported more pain during treatment.
Still, the findings of the present study should be interpreted with caution in the context of some limitations. First of all, our results lack external validity as we performed a single-center clinical trial with strict eligibility criteria, a relatively small number of participants, and a rather short follow-up. It should be stressed that the five dropouts, although not related to the study, might still have affected our findings. Since we could not handle missing data by applying the last-observation-carried-forward method due to the early time point of most dropouts or by performing a multiple imputation method due to the relatively small number of participants, we undertook a per-protocol analysis. Of interest, given that the sample size of our study was estimated based on the total number of participants with non-severe ED expected to attain an MCID in the IIEF-EF, our study was underpowered to perform any comparisons in patients with different degrees of ED (mild, mild to moderate, moderate). Moreover, it should be highlighted that the concentration of platelets and growth factors in a PRP fraction is predominantly based on the system used for its preparation.23 Since we performed all PRP preparations with the Magellan Autologous Platelet Separator, our results cannot be extrapolated to other PRP separation systems. Accordingly, even though we performed a quality control analysis of all PRP samples, we did not evaluate the qualitative or quantitative composition of growth factors, cytokines, or other molecules with regenerative properties. Therefore, the exact mechanism through which PRP improves erectile function remains unknown.
Indeed, to date, no consensus exists regarding the optimal platelet concentration in the PRP.25 Some studies report that the therapeutic effect of PRP requires platelet concentrations greater than 200,000/ mL, while others greater than 1,000,000/ mL.26 Based on the previous notion, PRP separation systems are divided into high- (platelet concentrations about 750,000/ mL) and low- (platelet concentrations about 500,000/ mL) yielding devices.27 The Magellan Autologous Platelet Separator used in our trial is considered a high-yielding device and, therefore, produces higher concentrations of platelets and, in turn, molecules with regenerative properties.23
*The beneficial effect of PRP in the regenerative and wound healing process is predominantly exerted through high concentrations of platelets and growth factors.28,29 In particular, platelets contain multiple regenerative molecules such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF-1), and fibroblast growth factor (FGF), that improve angiogenesis stimulation, stem cell recruitment, and inflammatory.30
CONCLUSION
Our findings demonstrate that two PRP intracavernosal injections within a one-month interval were safe and effective for the improvement of erectile function in patients with mild and moderate ED. Overall, PRP intracavernosal injection treatment, as a new representative of the flourishing field of regenerative medicine, seems to be a promising addition to the urologist’s armamentarium. Nevertheless, before it is accepted as part of the ED algorithm, further high-quality studies are warranted to corroborate our findings.
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 the final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated.
Results: At 6 months, an 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 were 3.9 points (95%CI: 1.8-5.9). Similarly, a statistically significant difference in both the number of participants attaining an 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 the 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.
INTRODUCTION
Vasculogenic erectile dysfunction (ED) is a complex, multidimensional disorder that predominantly manifests due to reduced penile blood flow, arterial insufficiency or stenosis, as well as endothelial dysfunction.1 Most recommended treatments improve erectile function by enhancing penile hemodynamics without reversing the pathophysiologic mechanisms leading to ED.2
Platelet-rich plasma (PRP) is an autologous plasma fraction produced from the centrifugation of whole blood that contains a 3- to 7-times higher mean platelet concentration compared to whole blood.3 Due to the beneficial properties of growth factors contained in high concentrations in this fraction, numerous medical specialties have included PRP injections in the quiver of their offered treatment options.4−9 Recently, PRP intracavernosal injections emerged as a promising, angiogenic, vasculogenic and regenerative treatment modality for ED.10 Animal studies postulate that PRP injections may improve key elements of the pathophysiologic mechanisms leading to ED through antiinflammatory, reparative, neuroprotective and neurotrophic effects.11−14 Still, these mechanisms are yet neither adequately explored nor completely understood.
Despite the favorable outcomes of PRP and the exploding interest in regenerative medicine, limited data support its use as part of the established ED therapeutic algorithm.15−17 Given the paucity of human clinical trials, there is currently an unmet need for high-quality studies exploring the use of PRP for the management of ED.18 In this scope, we conducted the first double-blind, randomized, placebo-controlled clinical trial aiming to assess the efficacy and safety of PRP injections versus placebo in patients with non-severe ED.
DISCUSSION
Our findings demonstrate that intracavernosal injections with PRP is a safe and effective treatment modality for the management of non-severe ED. Based on our results, two sessions of PRP led to a statistically significant improvement of the erectile function compared to placebo and this effect was maintained for 6 months. More than two-thirds of participants in the active arm presented an MCID in the IIEF-EF scale at all follow-up evaluations, demonstrating that the improvement in erectile function may be clinically important. Furthermore, no major or minor adverse events occurred during the treatment and follow-up period. Of note, subjects receiving PRP displayed higher satisfaction rates compared to placebo, while subjects receiving placebo injections reported more pain during treatment.
Still, the findings of the present study should be interpreted with caution in the context of some limitations. First of all, our results lack external validity as we performed a single-center clinical trial with strict eligibility criteria, a relatively small number of participants, and a rather short follow-up. It should be stressed that the five dropouts, although not related to the study, might still have affected our findings. Since we could not handle missing data by applying the last-observation-carried-forward method due to the early time point of most dropouts or by performing a multiple imputation method due to the relatively small number of participants, we undertook a per-protocol analysis. Of interest, given that the sample size of our study was estimated based on the total number of participants with non-severe ED expected to attain an MCID in the IIEF-EF, our study was underpowered to perform any comparisons in patients with different degrees of ED (mild, mild to moderate, moderate). Moreover, it should be highlighted that the concentration of platelets and growth factors in a PRP fraction is predominantly based on the system used for its preparation.23 Since we performed all PRP preparations with the Magellan Autologous Platelet Separator, our results cannot be extrapolated to other PRP separation systems. Accordingly, even though we performed a quality control analysis of all PRP samples, we did not evaluate the qualitative or quantitative composition of growth factors, cytokines, or other molecules with regenerative properties. Therefore, the exact mechanism through which PRP improves erectile function remains unknown.
Indeed, to date, no consensus exists regarding the optimal platelet concentration in the PRP.25 Some studies report that the therapeutic effect of PRP requires platelet concentrations greater than 200,000/ mL, while others greater than 1,000,000/ mL.26 Based on the previous notion, PRP separation systems are divided into high- (platelet concentrations about 750,000/ mL) and low- (platelet concentrations about 500,000/ mL) yielding devices.27 The Magellan Autologous Platelet Separator used in our trial is considered a high-yielding device and, therefore, produces higher concentrations of platelets and, in turn, molecules with regenerative properties.23
*The beneficial effect of PRP in the regenerative and wound healing process is predominantly exerted through high concentrations of platelets and growth factors.28,29 In particular, platelets contain multiple regenerative molecules such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF-1), and fibroblast growth factor (FGF), that improve angiogenesis stimulation, stem cell recruitment, and inflammatory.30
CONCLUSION
Our findings demonstrate that two PRP intracavernosal injections within a one-month interval were safe and effective for the improvement of erectile function in patients with mild and moderate ED. Overall, PRP intracavernosal injection treatment, as a new representative of the flourishing field of regenerative medicine, seems to be a promising addition to the urologist’s armamentarium. Nevertheless, before it is accepted as part of the ED algorithm, further high-quality studies are warranted to corroborate our findings.
