Abstract
Purpose
Erectile dysfunction (ED) significantly impacts quality of life and intimate relationships. ED results from a complex interaction of physiological, psychological, and lifestyle factors. While conventional treatments focus on symptom management, regenerative therapies like platelet-rich plasma (PRP) aim to address underlying causes, offering curative potential. However, evidence for PRP’s efficacy in vasculogenic ED remains inconclusive. This systematic review and meta-analysis (SRMA) evaluates the effectiveness of penile PRP injections for vasculogenic ED and updates clinical guidelines based on recent evidence.
Materials and Methods
Conducted per MOOSE guidelines and registered with PROSPERO (CRD42023430295), this SRMA included observational studies and randomized controlled trials (RCTs) assessing PRP for vasculogenic ED. The PECOS framework guided eligibility, focusing on RCTs comparing PRP to placebo for meta-analysis. Data on study characteristics, PRP protocols, and outcomes using validated erectile function measures and penile Doppler parameters were extracted. Quality was assessed using Cochrane risk of bias and CONSORT guidelines. Statistical analysis employed random or fixed-effects models based on heterogeneity, with publication bias evaluated via funnel plots.
Results
Of 111 abstracts screened, 28 met inclusion criteria, and 3 RCTs alongside 2 observational comparative studies were reviewed. Meta-analysis of the RCTs showed significant improvement in erectile function for PRP versus placebo (mean difference 3.28, 95% confidence interval 1.46–5.11, p<0.001). Sensitivity analysis confirmed result's robustness, and no publication bias was detected. Side effects were rare, with isolated cases of plaque formation and hematoma. Studies combining PRP with low-intensity shock wave therapy showed enhanced efficacy.
Conclusions
PRP therapy appears promising for vasculogenic ED, but additional research is necessary to establish definitive clinical guidelines.
Keywords: Erectile dysfunction, Meta-analysis, Platelet-rich plasma, Regenerative medicine, Systematic review
INTRODUCTION
Erectile dysfunction (ED) is a common medical condition characterized by the inability to achieve or maintain an erection sufficient for satisfactory sexual performance [1,2]. This disorder significantly impacts an individual's quality of life and intimate relationships [3,4]. The prevalence of ED is predicted to rise to nearly 322 million cases globally by 2025 [5]. ED is a multifactorial condition that can result from a diverse interplay of physiological, psychological, and lifestyle determinants. Key contributors include vascular pathologies, such as atherosclerosis; endocrine disruptions like hypogonadism; neurogenic disorders, including diabetic neuropathy; adverse effects of pharmacological agents; and psychosocial stressors that may exacerbate underlying vulnerabilities. The intricate interrelationship between these factors necessitates a comprehensive and individualized diagnostic approach to manage and treat ED effectively.
ED management encompasses a spectrum of therapeutic approaches, each tailored to the severity of the condition and patient response. A structured, stepwise strategy is advised, beginning with first-line oral pharmacotherapy using phosphodiesterase type 5 inhibitors (PDE-5is) [6]. For patients who do not achieve satisfactory results with oral agents, escalation to more invasive treatments is recommended. These include the use of vacuum erection devices [7], intracavernosal injection therapy [8], and, for refractory cases, surgical interventions such as penile prosthesis implantation [9]. Each modality offers distinct benefits and considerations, necessitating a personalized approach to optimize outcomes. Despite the current evidence, contemporary ED medical treatments do not have a role in reversing the cause underlying ED and require on-demand or daily use.
Recent advancements in regenerative medicine have introduced innovative therapeutic modalities, such as penile low-intensity shock wave therapy (Li-ESWT) [10] and penile platelet-rich plasma (PRP) injections [1]. These approaches are based on a potential regenerative effect on the cavernous tissue and, consequently, on the erectile mechanism, and they could become promising alternatives to conventional treatments for male sexual dysfunction.
Only a few studies are available on PRP, and these are characterized by a high degree of variability in their protocols, including the volume of plasma used, the number of injections, and the timing of intracavernosal injections.
Although a few recent randomized controlled trials (RCTs) have been published, no conclusive recommendations can be drawn about the actual effect of penile PRP in vasculogenic ED. The European Association of Urology (EAU) guidelines recommend that further studies are needed for PRP and stem cell therapy (SCT) to achieve adequate evidence-based and clinically reliable recommendation grades [2]. However, the European Society for Sexual Medicine position statements indicate that PRP should always be used within clinical trials for vasculogenic-based ED [11].
The present systematic review and meta-analysis (SRMA) aims to rigorously evaluate and synthesize the current evidence regarding the efficacy of penile PRP injections in vasculogenic ED, providing an up-to-date guideline for clinicians on their clinical use.
MATERIALS AND METHODS
1. Protocol and registration
This SRMA was performed following the Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE) guidelines [12]. This systematic review was registered a priori with the PROSPERO database (CRD42023430295). The Global Andrology Forum Internal Review Board approved this study.
2. Study design and eligibility
This SRMA encompassed human observational studies (including case-control and cohort studies) and RCTs investigating the outcomes of PRP injection in sexually active adult men diagnosed with vasculogenic ED. A specific population (P), intervention (I), comparator (C), outcome (O) and study design (S) (PICOS) framework was used to define study eligibility (Supplement Table 1).
All studies assessing the impact of PRP on men with vasculogenic ED were incorporated into the systematic review, irrespective of patient characteristics, PRP preparation protocols, dosage, injection techniques, or concomitant adjuvant therapies. However, for the meta-analysis, only RCTs that compared PRP injections with placebo were included to maintain a rigorous evaluation of efficacy.
3. Study outcomes
The primary outcome of the study was the change in erectile function from baseline using the following validated questionnaires:
• International Index of Erectile Function-Erectile Function (IIEF-EF) [13]
• Erection Hardness Score (EHS) [14]
• Sexual Encounter Profile Diary (SEP) Q2 and Q3 [15]
• Global Assessment Questions (GAQ) [16]
• Sexual health inventory for men (SHIM) [17]
The secondary outcomes included any vascular parameter variation during penile duplex ultrasound, treatment-related pain defined as a quantitative assessment using visual analog scale (VAS) score [18], adverse events related to PRP injection and long-term results of PRP therapy.
4. Exclusion criteria
We excluded articles published as abstracts, conference papers, case reports, case series, reviews, book chapters, and animal studies.
5. Search strategy
A comprehensive systematic search was conducted via Scopus and PubMed databases using a combination of Medical Subject Heading (MeSH) terms and free words. An initial keyword string was created on Scopus: "TITLE-ABS-KEY (erectile dysfunction OR erectile function) AND (platelet rich plasma) AND (LIMIT-TO (DOCTYPE, "ar")). For PubMed, the following keyword string was used ((((((platelet rich plasma ) AND ((dysfunction, erectile[MeSH Terms]) OR (erection, penile[MeSH Terms]) OR (erectile function))))) NOT (Peyronie disease[MeSH Terms]). The databases were searched for studies published until June 2024. All English and non-English articles were included in the search. The search was filtered for males and humans. After removing duplicates, investigators (VK, JFS, TM, MDD) independently screened the titles and abstracts of identified records for eligibility following inclusion/exclusion criteria and the PICOS model. The full texts of all potentially eligible records were then screened by two independent investigators (HK, MP). Disagreements were resolved by discussing or consulting a third investigator (MF).
6. Data extraction
Data were extracted for potentially eligible articles whose full text was available. In the case of missing data, the original study's authors were contacted.
The extracted data included the following:
• Study characteristics (author’s name, journal, year of publication, study design, sample size [total and by group])
• Baseline demographic and clinical characteristics of the participants (age; medical comorbidities; unique habits, e.g., smoking; duration of ED; ED scores using different tools, e.g., IIEF-EF, IIEF-5, SEP, SHIM, and EHS; and penile Doppler parameters, e.g., peak-systolic velocity [PSV], end-systolic velocity [EDV], and resistance index [RI])
• Details of PRP therapy (indication for PRP, duration of PRP, dose of PRP injected, number of PRP sessions, adverse effects, long-term results of PRP, follow-up duration)
• Adjuvant therapies (e.g., PDE-5i or others)
• Post-intervention parameters (ED scores using different tools, e.g., IIEF-EF, IIEF-5, SEP, SHIM, and EHS; and penile Doppler parameters, e.g., PSV, EDV, and RI)
7. Assessment of quality of included studies
The quality of the included RCTs was assessed using the Cochrane risk of bias [19] and CONSORT guidelines [20]. Two independent investigators (HK, MP) assessed each study's quality scores. Disagreements were resolved by discussing or consulting a third investigator (MF).
8. Statistical analysis
The results of the studies evaluating PRP injections in men with vasculogenic ED were pooled via meta-analysis. The mean difference (MD) was used as the effect size of the meta-analysis.
The I2 statistic and the Cochrane Q test evaluated the in-between study heterogeneity. Moderate heterogeneity was considered if the I2 was >40%, and a p-value of <0.1 was considered significant heterogeneity. Random and fixed effects models were used for high and low heterogeneity, respectively. The restricted maximum-likelihood estimator was used to calculate the in-between study variance (τ2), and the inverse variance method was used to pool the effect size. Publication bias was assessed using the funnel plot. Sensitivity analysis was performed by excluding one study at a time (leave-one-out method) and observing the changes in the pooled effect size. A study is sensitive when it significantly changes the pooled effect size when it is removed. The statistical analysis was performed using the R programming language R version 4.1.2 (https://www.r-project.org/) with a p-value of <0.05, considered statistically significant for the overall difference between groups.
RESULTS
1. Results of the literature search
By applying the aforementioned search strategy, 111 abstracts were identified. After removing duplicates and screening records from titles and abstracts, 28 articles were deemed eligible and were reviewed. The full texts of all potentially eligible records were then reviewed. Finally, 3 RCTs [21,22,23] and 2 observational comparative studies [24,25] met the inclusion criteria and were included in the systematic review process. Only 3 RCT articles were considered for meta-analysis. The Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) flowchart summarizing the literature search and article selection is shown in Fig. 1.
Fig. 1. PRISMA flowchart summarizing the literature search and article selection. RCT: randomized controlled trial.
2. Quality of the included studies
Table 1 summarizes the quality check of the RCTs using the Cochrane risk of bias and CONSORT guidelines.
Table 1. Quality checklist of randomized controlled trials (Cochrane and CONSORT checklist).
3. Patient features and basic erectile function parameters
Table 2 summarizes the extracted data of the 3 RCTs included in the meta-analysis. Additionally, two observational comparative studies were included in the systematic review.
Table 2. Summary of the extracted data from the systematic review and meta-analysis.
| Study | Country | Study design | Study period | Treatment | No. of patients | Age (IQR) | ED duration (IQR) | IIEF-EF pre (SD) | SEP Q2 pre (yes, %) | SEP Q3 pre (yes, %) | Doppler US pre (cm/sec) | Follow up (mo) | IIEF-EF post (SD) | SEP Q2 post (yes, %) | SEP Q3 post (yes, %) | Doppler US post (cm/sec) | VAS scale | Adverse event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Poulios et al [21] | Greece | Prospective double-blind RCT | 2019–2020 | Group A: PRP | Total: 60 | Total: NA | Total: 66 (48–120) | Group A: 20.4 (2.9) | NA | Group A: 47.5 (20.1) | NA | 6 mo | Group A: 23.9 (1)* | NA | Group A: 68 (5)* | NA | Group A: 2.2 (SD 0.6) | None |
| Group B: placebo (saline) | Group A: 30 | Group A: 58 (51.5–62) | Group A: 78 (48–120) | Group B: 19.4 (3.7) | Group B: 45.8 (22.8) | Group B: 19 (1) | Group B: 39 (4.5) | Group B: 2.6 (SD 0.4) | ||||||||||
| Group B: 30 | Group B: 59 (53.5–61) | Group B: 60 (39–117) | ||||||||||||||||
| Masterson et al [22] | USA | Prospective double-blind, placebo, RCT | 2020–2022 | Group A: PRP | Total: 61 | Total: NA | - | Group A: 17.4 (1.6) | NA | NA | Group A: PSV 47.2 (42.1– 52.4) | 6 mo | Group A: 22.2 (3.2)* | NA | NA | Group A: PSV 48.8 (42.5–56.7) | Group A: 4.1 | Group A: 1 case of new plaque |
| Group B: placebo (saline) | Group A: 28 | Group A: 49 (38.5–55) | Group B: 18.6 (1.3) | Group B: PSV 40.5 (36.9–44.1) | Group B: 20.5 (2)* | Group B: PSV 44.7 (36.5–55.8) | Group B: 4 | Group B: 1 case of hematoma | ||||||||||
| Group B: 33 | Group B: 46 (42–56) | |||||||||||||||||
| Shaher et al [23] | Egypt | Prospective double-blind RCT | 2020–2021 | Group A: PRP | Total: 100 | Total: NA | Total: 43.5 (34.2–53) | Group A: 18 (17–22) | Group A: 12 (24) | Group A: 0 | Group A: PSV 19 (16–23), EDV 6 (5–7) | 6 mo | Group A: 22 (19.7–24.2)* | Group A: 37 (74)* | Group A: 33 (66)* | Group A: PSV 33 (30–35.2)*, EDV 1 (0–2.25)* | Group A: 1.52 (SD 1.2) | None |
| Group B: placebo (saline) | Group A: 50 | Group A: 57 (46–65) | Group A: 44.5 (33–53.3) | Group B: 19 (17–22) | Group B: 15 (30) | Group B: 0 | Group B: PSV 19.5 (16–24), EDV 6 (5–7) | Group B: 19 (17–22) | Group B: 11 (22) | Group B: 0 | Group B: PSV 20 (16–23.2), EDV 6 (5–7) | Group B: 1.54 (SD 1.3) | ||||||
| Group B: 50 | Group B: 54 (45–64) | Group B: 41.5 (35–53.5) | ||||||||||||||||
| Geyik et al [24] | Türkiye | Retrospective comparative study | 2015–2020 | Group A: Li-ESWT | Total: 184 | Total: NA | Group A: 47.64 (SD 35.64) | Group A: 14.33 (4.39) | NA | NA | NA | 6 mo | Group A: 17.82 (3.44)* | NA | NA | NA | NA | Group A: 0 |
| Group B: Li-ESWT + PRP | Group A: 93 | Group A: 51.28 (SD 11.43) | Group B: 47.64 (SD 31.68) | Group B: 17.82 (3.44) | Group B: 26.3 (2.55)* | Group B: 24 (26.4%) Mild penile bruising after the injection |
||||||||||||
| Group B: 91 | Group B: 46.7 (SD 11.86) | |||||||||||||||||
| Sajjad et al [25] | Pakistan | Prospective comparative study | 2019–2020 | Group A: Li-ESWT | Total: 60 | Total: NA | NA | NA | NA | NA | NA | 3 mo | Group A: 20.21* | NA | NA | NA | NA | NA |
| Group B: PRP | Group A: 30 | Group A: 42.56 (SD 7.44) | Group B: 21.26* | |||||||||||||||
| Group B: 30 | Group B: 45.89 (SD 9.11) |
ED: erectile dysfunction, IIEF: International Index of Erectile Function, EF: erectile function domain (of IIEF), IQR: interquartile range, SD: standard deviation, SEP: sexual encounter profile, Q: question, US: ultrasound scan, VAS: visual analog scale, RCT: randomized controlled trial, PRP: platelet-rich plasma, Li-ESWT: low-intensity shock wave therapy, PSV: peak systolic velocity, EDV: end-diastolic velocity, NA: not available.
*Statistically significant p-values compared to baseline.
Three prospective, double-masked RCTs comparing PRP injections to placebo (saline solution injections) with a minimum follow-up period of 6 months were included in the SRMA. On the other hand, the two comparative observational studies that considered a combination of regenerative therapies (PRP with Li-ESWT vs Li-ESWT) were included in the systematic review process only.
Overall, most of the patients' basic features and erectile function parameters were found to be sporadic and inconsistent among the studies. ED duration was reported in 2 studies only [21,23], with a range of 43.5 to 66 months. The pooled estimate was not significantly different between the compared groups (MD 3.58, 95% confidence interval [95% CI] -0.1–7.3; p=0.06).
All three RCT studies reported baseline and posttreatment IIEF-EF [21,22,23]. The pooled estimate was not significantly different between the compared groups (MD -0.6, 95% CI -1.8–0.54; p=0.3). The meta-analysis included 107 and 113 patients in the PRP and placebo groups. The pooled estimate was significantly greater in the PRP group (MD 3.28, 95% CI 1.46–5.11; p<0.001; Fig. 2). No publication bias was found in the qualitative analysis, as supported by the symmetry of the funnel plot (Fig. 3). Sensitivity analysis revealed that no studies influenced the pooled estimate when removed (Fig. 4).
Fig. 2. Forest plot of IIEF-EF after PRP and placebo. SD: standard deviation, MD: mean difference, CI: confidence interval, IIEF-EF: International Index of Erectile Function-Erectile Function, PRP: platelet-rich plasma.
Fig. 3. Funnel plot of IIEF-EF after PRP and placebo. IIEF-EF: International Index of Erectile Function-Erectile Function, PRP: platelet-rich plasma.
Fig. 4. Sensitivity analysis of IIEF-EF after PRP and placebo. MD: mean difference, CI: confidence interval, IIEF-EF: International Index of Erectile Function-Erectile Function.
Concerning baseline and post-treatment SEP Q2 and SEP Q3 analyses, the number of studies reporting value was <2; therefore, no meta-analysis was performed. Side effects were reported in all the studies [21,22,23]. However, only Masterson et al [22] described a single case of new plaque formation in the PRP group (without further information) and one case of hematoma in the placebo group. The other authors did not report any adverse events in their series.
The results of the comparative study of PRP with Li-ESWT treatment were consistent with the adjuvant role of the combination of PRP and Li-ESWT.
DISCUSSION
When applied to ED, the goal of regenerative therapies is to improve the quality of erectile tissue in order to achieve long-term improvement and restoration of erectile function [1,26]. PRP is an autologous regenerative therapy derived from the patient whole blood and contains a concentrated supraphysiological mixture of platelets (>106 U/mL), growth factors and other proteins (cytokines and chemokines) [27]. PRP originated in the 1970s and has been utilized across various medical specialties for its potential to accelerate tissue repair, promote angiogenesis, and stimulate cellular proliferation and regeneration as a promising avenue in regenerative medicine. Early on, hematologists recognized the potential of platelets for tissue repair, leading to the development of methods to isolate and concentrate platelets from whole blood. Since the 1990s and 2000s, advancements in PRP technology have continued to refine its therapeutic potential. Preclinical and clinical studies have increasingly explored the mechanisms of action of PRP, with a focus on its ability to release growth factors and cytokines to foster cellular proliferation and tissue repair. Today, PRP therapy stands as a widely used, minimally invasive treatment option for musculoskeletal, dental, dermatological, and, recently, gynecologic conditions like endometrial disease and premature ovarian failure [28,29].
Refinements in PRP preparation techniques and an expanding body of research have bolstered its efficacy in stimulating tissue regeneration. Current research is investigating its potential applications in addressing vascular disorders such as vasculogenic ED [30].
The beneficial effect of PRP in the regenerative and wound healing process is predominantly exerted through high concentrations of platelets and growth factor injected into injury sites [21,31]. Platelets play a crucial role in coagulation and wound healing following injury and contain multiple regenerative molecules, including cytokines and adhesion proteins, which are responsible for initiating the hemostatic cascade, synthesizing new connective tissue, and revascularization [32,33].
Among the growth factors locally released by PRP administration, angiopoietin-2, vascular endothelial growth factor, platelet-derived growth factor, endodermal growth factor, transforming growth factor-β1, insulin-like growth factor-1 and fibroblast growth factor improve angiogenesis stimulation, stem cell recruitment, neuronal regeneration, modulate the inflammatory response and promote connective tissue healing by drawing cells into the newly created extracellular matrix [34,35]. These compounds have enhanced erectile function in preclinical and clinical trials [36,37].
In a rat model, Wu et al [38] showed the impact of PRP on the recovery of erectile function following bilateral cavernous nerve damage (decreased apoptotic markers and fibrosis). In another rat model of ED linked to hyperlipidemia, Huang et al [39] examined the effectiveness of PRP therapy for compromised penile hemodynamics. They reported significantly increased eNOS protein levels, increased anti-rat endothelial cell antigen-1 staining in the corpus cavernosum, decreased intracorporal oxidative stress and apoptotic indices, and increased intracavernous pressure in the PRP group. Ding et al [40] revealed that PRP administration results in a significantly greater mean maximal intracavernosal pressure (ICP) and maximum ICP/MAP (mean arterial pressure) ratio. Furthermore, from a histological point of view, the PRP group presented more myelinated axons. While preclinical studies in animal models have demonstrated promising results for PRP in treating ED, a significant gap in successfully translating these findings to human clinical studies. This disconnect can be attributed to several factors: differences in physiology and anatomy (variations in structure and function of penile tissues); differences in disease etiology and progression (animal models frequently use induce ED that does not encompass the full spectrum of the disease's causes and progression in humans); different dosing and treatment duration (in animal models the protocols are often optimized for rapid observation of effects which may not align with the response in human tissues).
In general, all three RCTs [21,22,23] highlighted a beneficial effect of PRP therapy on erectile function compared with placebo treatment, demonstrating a significant improvement in the IIEF-EF questionnaire scores between pre-and post-treatment values. This finding has also been confirmed by other recently published SRMAs on the topic [35,41]. Specifically, Poulios et al [21] reported a MD IIEF-EF, compared with placebo, of 4.9 (95% CI 4.39–5.41). Masterson et al [22] reported a MD of 1.7 (95% CI 0.33–3.07) between the IIEF-EF scores of the placebo and PRP groups. These studies had a similar population of 29 and 28 participants receiving PRP, respectively. A more extensive study by Shaher et al [23] with 50 participants each receiving PRP and placebo showed a MD of 3 (95% CI 2.07–3.93) in their IIEF-EF scores after treatment. Our meta-analysis showed a MD of 3.28 (95% CI 1.46–5.11) in the IIEF-EF scores when comparing 107 patients receiving PRP and 113 patients receiving placebo. The results supporting the effect of PRP compared to placebo are confirmed up to 6 months of follow-up, and data indicated that the improvement in erectile function following PRP treatment appeared to become more pronounced over time [35,41]. Regarding satisfaction assessed with the SEP Q3, a significant difference was reported after PRP treatment versus placebo.
Moreover, two studies [22,23] reported the vascular data from dynamic penile Doppler ultrasound before and after PRP treatment. Shaher et al [23] reported a significant increase in the caliber of the cavernous artery, PSV, and end-diastolic velocity post-PRP therapy compared with those in the placebo group.
Concerning the safety profile, no major or minor adverse events occurred during the treatment follow-up period. Additionally, there was no significant difference in the VAS score between the studied groups [22,23]. In a single case, Masterson et al [22] reported asymptomatic plaque formation in one patient after PRP; this outcome was not observed in other groups treated with PRP, therefore, a definitive causal link between PRP injection and penile plaque formation cannot be established. While PRP therapy is generally safe, specific patient populations may not be appropriate candidates for this treatment. Studies have shown that individuals with platelet dysfunction, unstable hemodynamics, anticoagulation therapy, or sepsis should avoid PRP therapy [42]. Nonetheless, the exact histological and biomolecular pathway changes are yet to be determined. Clinical governance and regulation are important aspects that will be developed in the coming years.
To date, major scientific societies have interpreted the available data on the use of PRP in clinical practice in a non-uniform manner, as summarized in Table 3. However, all societies agree that further well-conducted and reliable studies are needed to draw definitive conclusions.
Table 3. Recommendations from scientific society about PRP injections and clinical application.
| Scientific society | Recommendation | Strength rating | Level of evidence |
|---|---|---|---|
| European Association of Urology (EAU) (2024) | Intracavernous injections of PRP have led to a mild improvement of EF among patients with organic ED, but the available evidence is still insufficient to provide a recommendation regarding its use | NA | NA |
| European Society for Sexual Medicine (ESSM) (2024) | Cell therapy for male sexual dysfunction and should be considered a treatment under investigation and should not be offered outside of clinical trials approved by an ethics committee | Good Clinical Practice Statement | NA |
| International Society for Sexual Medicine (ISSM) (2021) | Additional research (further high-quality studies) should focus on PRP protocols for ED treatment and whether PRP would be suitable as a single therapy or as a part of combination approach | NA | NA |
| American Urological Association (AUA) (2018) | For men with ED, PRP therapy should be considered experimental (in the context of an Institutional Review Board-approved experimental clinical research protocol) | Expert opinion | NA |
PRP: platelet-rich plasma, EF: erectile function domain (of IIEF), ED: erectile dysfunction, NA: not available.
Among novel regenerative therapies for ED, SCT has also emerged as a promising approach. PRP and SCT aim to address the underlying pathophysiological mechanisms of ED, but they do so through different mechanisms. As previously discussed, PRP therapy primarily releases growth factor and cytokines that promote healing and angiogenesis. In contrast, SCT involves the transplantation of stem cells that have the potential to differentiate into various cell types (multipoint cells), potentially leading to more comprehensive tissue repair and regeneration [43].
Compared to PRP, SCT may provide more robust and longer-lasting effects due to its ability to directly replace or repair damaged tissues and promote a more extensive regenerative response. Despite these potential advantages, SCT is often associated with higher costs, more complex preparation and administration protocols, and more significant regulatory challenges than PRP [43]. Moreover, while both therapies have shown promising results in preclinical studies, the clinical evidence is still evolving, with a growing body of clinical data supporting PRP use while limited evidence for SCT efficacy and safety in human populations.
Table 2 also reports the initial experiences of using PRP compared to and combined with Li-ESWT. In these series, the erection parameters evaluated with the IIEF-EF questionnaire show better post-treatment results, especially when the two therapies are combined [24,25]. These data, if confirmed after better-designed RCTs, might lay the groundwork for a synergistic approach of combined therapies for managing patients with vasculogenic ED, aiming to achieve a significant and lasting improvement in erectile function.
Studies have shown notable improvements in ED symptoms following PRP treatment, highlighting its effectiveness as a complementary or alternative approach to traditional therapies like PDE-5i or surgical interventions. These results suggest that the healing and regenerative properties of PRP might offer a promising avenue for enhancing erectile function in men with vasculogenic ED without significant severe side effects.
Among the various non-randomized series about PRP therapy for ED, the Francomano et al [44] series is particularly noteworthy. In this series, the effectiveness of PRP treatment was evaluated in a challenging cohort of ED patients unresponsive to PDE-5i. PRP therapy led to significant short-term (after one month) improvements in erectile function, with 80% of patients recovering responsiveness to PDE-5i. The study, moreover, noted an almost 7-point increase in the IIEF-5 score and enhancements in penile vascular parameters as assessed by Doppler ultrasound (PSV). Notably, the study also explored the predictive value of mean platelet volume (MPV), finding that MPV may be a valuable biomarker for assessing treatment outcomes, identifying an MPV <8.96 fL as an optimal threshold for predicting favorable clinical responses to PRP therapy [44].
Interpreting all studies' findings warrants caution due to several inherent limitations.
Notably, many advanced PRP separation systems on the market utilize calcium chloride or thrombin during preparation to activate platelets, thereby promoting the release of growth factors before intracavernous injection [36]. The efficacy of PRP is highly dependent on the platelet concentration achieved during the preparation phase, which introduces variability [30]. A significant limitation within the current literature, and consequently within this SRMA, is the lack of standardization across multiple critical variables: selection of separation kits, PRP preparation methodologies, qualitative evaluation of the PRP, and protocols for injection.
Comparing the three RCTs [21,22,23] included in this analysis regarding the preparation and administration protocol reveals some non-negligible differences.
Masterson et al [22] prepared PRP using the Arthrex Angel PRP system, an automated device with an optical sensor, to yield a highly concentrated and consistent PRP product. 120 mL of autologous blood was drawn from each patient, and approximately 5 mL of PRP was extracted following centrifugation. The PRP was administered via intracavernosal injection in two sessions, separated by a 1-month interval. The PRP was divided into two 2.5 mL syringes in each session before administration. In contrast, Shaher et al [23] employed a manual preparation method using standard centrifugation techniques. In this protocol, 30 mL of autologous blood was drawn from each patient, and the PRP was prepared through a two-step centrifugation process: 5 minutes at 2,500 RPM followed by 10 minutes at 3,500 RPM. The final volume of PRP obtained was 6 mL, which was injected into each corpus cavernosum (3 mL per side) across three different injection sites. The injections were administered in three sessions with a 15-day interval between each.
The study by Poulios et al [21] did not specify the details of the PRP preparation method but described a protocol involving two intracavernosal injections of PRP, each consisting of 10 mL, with a 1-month interval between injections. The lack of detailed information on the preparation technique limits direct comparison with the other two studies; however, the total volume of PRP used per injection was significantly higher than that in the studies by Masterson et al [22] and Shaher et al [23]. These differences in PRP preparation methods, including the volume of blood drawn, centrifugation techniques, and injection protocols, likely contribute to the variability in clinical outcomes observed across the studies.
Moreover, more consensus remains to be reached regarding the optimal number of injections, the volume administered per session, or the intervals between injections, all of which further complicate the reproducibility and generalizability of results [45].
Therefore, the need for uniformity in the concentration of PRP and the separation system used among the included studies is a limiting factor of this review. Further studies are warranted to optimize PRP preparation and administration protocols for ED treatment.
In addition to these intrinsic limitations related to PRP preparation, other structural limitations of the different series should be considered, such as patient heterogeneity, small sample sizes, lack of control groups, single-center experiences and limited follow-up periods, which do not allow for long-term conclusions on the sustained efficacy of PRP treatment (Supplement Fig. 1). Given the current limitations in the literature, the EAU [2] and the American Urological Association [46] indicate that PRP administration should be applicable only within study protocols approved by an Institutional Review Board.
Moreover, future studies should analyze the efficacy of PRP as part of monotherapy or combination treatment for ED. This includes evaluating PRP compared with PDE-5i and Li-ESWT and trials assessing the synergistic effect of PRP with such recommended treatments.
Our SRMA’s rigorous methodology and a summary of international society recommendations present a unified perspective beyond the conclusions of other recently published SRMAs on the same topic.
CONCLUSIONS
The limited current data suggests that PRP may be useful in treating some cases of vasculogenic ED. However, the injected dose, preparation technique, time interval between injections, and clinical utility need further validation through larger RCTs. Further studies are warranted to validate the results of the present SRMA.
Acknowledgements
The authors wish to thank the following experts for offering valuable comments on our manuscript: Prof. Eric Chung (Australia), Prof. Selahittin Cayan (Turkey), and Dr. Germar-M Pinggera (Austria).
Footnotes
Conflict of Interest: The authors have nothing to disclose.
Funding: None.
- Conceptualization: MF.
- Statistical analysis: AMH.
- Supervision: MF, RS, AA.
- Writing – original draft: MP, HK, JFSV, RB, TM, MDD, VK, RP, TS, AHI, AB.
- Writing: all authors.
- Review and editing: MF, RS, AA.
- All authors have read and agreed to the published version of the manuscript.
Supplementary Materials
Supplementary materials can be found via https://doi.org/10.5534/wjmh.240310.
SWOT analysis of systematic review and meta-analysis on PRP. SRMA: systematic review and metaanalysis, PRP: platelet-rich plasma.
Population, Intervention, Comparator, and Outcomes (PICO) model of the current study
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
SWOT analysis of systematic review and meta-analysis on PRP. SRMA: systematic review and metaanalysis, PRP: platelet-rich plasma.
Population, Intervention, Comparator, and Outcomes (PICO) model of the current study