|Year : 2021 | Volume
| Issue : 4 | Page : 171-176
A short term follow up for intracavernosal injection of platelet rich plasma for the treatment of erectile dysfunction
Shin-Mei Wong1, Bing-Juin Chiang2, Hui-Chun Chen3, Yi-No Wu4, Ying-Hung Lin5, Chun-Hou Liao6
1 Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan
2 Division of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei City; Department of Life Science, College of Science, National Taiwan Normal University, Taipei; School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
3 Department of Nursing, Chang Gung University of Science and Technology, New Taipei City, Taiwan
4 School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
5 Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, New Taipei City, Taiwan
6 Division of Urology, Department of Surgery, Cardinal Tien Hospital; School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
|Date of Submission||24-Jan-2021|
|Date of Decision||16-Apr-2021|
|Date of Acceptance||01-Jun-2021|
|Date of Web Publication||14-Dec-2021|
Prof. Chun-Hou Liao
Divisions of Urology, Department of Surgery, Cardinal Tien Hospital, No. 362, Zhong-Zheng Road, XinDian District, New Taipei City 23148
Assoc. Prof. Ying-Hung Lin
Graduate Institute of Biomedical and Pharmaceutical Science, Fu-Jen Catholic University, No. 510 Zhongzheng Road, Xinzhuang District, New Taipei City 242
Source of Support: None, Conflict of Interest: None
Purpose: The objective of this study was to investigate the safety and efficacy of intracavernosal platelet-rich plasma (PRP) injection in patients with erectile dysfunction (ED). Materials and Methods: Between September 2018 and September 2020, thirty participants with ED were enrolled in this prospective single-arm study. All participants received three sessions of intracavernosal PRP injection. Oral phosphodiesterase type 5 (PDE5) inhibitors or testosterone replacement therapy (TRT) without a change in dosing was permitted during the treatment period. Efficacy was assessed using the International Index of Erectile Function-5 (IIEF-5), Erectile Hardness Score (EHS), Sexual Encounter Profile (SEP) 2 and 3, and Global Assessment Question, every 2 weeks after each treatment session. Any adverse events were recorded. Results: The mean age of participants was 54.93 years. Oral PDE5 inhibitors were prescribed to 76.7% of participants (n = 23), and 50% of participants (n = 15) received concurrent TRT. A significant improvement in erectile function was measured by an average of 4.556 points in IIEF-5 (P < 0.001) and 0.72 points in EHS (P < 0.001). In total, 4 (13.3%) and 15 (50%) participants reported “no” to “yes” in SEP2 and SEP3 questions after therapy, respectively. Overall, 82.8% of participants agreed that the study therapy improved erectile function. No significant adverse events were reported. Conclusion: This single-arm prospective study revealed that preliminary experience with penile PRP significantly improves erectile function without obvious adverse events.
Keywords: Erectile dysfunction, intracavernous platelet-rich plasma, platelet-rich plasma
|How to cite this article:|
Wong SM, Chiang BJ, Chen HC, Wu YN, Lin YH, Liao CH. A short term follow up for intracavernosal injection of platelet rich plasma for the treatment of erectile dysfunction. Urol Sci 2021;32:171-6
|How to cite this URL:|
Wong SM, Chiang BJ, Chen HC, Wu YN, Lin YH, Liao CH. A short term follow up for intracavernosal injection of platelet rich plasma for the treatment of erectile dysfunction. Urol Sci [serial online] 2021 [cited 2022 Aug 13];32:171-6. Available from: https://www.e-urol-sci.com/text.asp?2021/32/4/171/332408
| Introduction|| |
Erectile dysfunction (ED) is a common, multifaceted sexual dysfunction that strongly affects the quality of life in men, both personally and socially. ED incidence increases with age. In 1994, the Massachusetts Male Aging Study, a cross-sectional, multidisciplinary epidemiologic survey of ED, revealed a 52% prevalence among individuals aged 40–70 years. The causes of ED vary and may include drugs, neuropathy, corpora cavernosa disease, psychological disorders, surgeries, aging, renal insufficiency, diabetes, smoking, and metabolic syndrome.,,,, The 2018 American Urological Association guidelines recommend personalized treatment for ED. For patients with comorbid health conditions or modifiable risk factors, lifestyle change is always the first step of the approach. Oral phosphodiesterase type 5 (PDE5) inhibitors remain the mainstay of ED treatment. Typically, 70% of patients who receive PDE5 inhibitors achieve successful sexual intercourse. For patients with hypogonadism-related ED, several testosterone preparations can provide better sexual satisfaction and increase libido. Alternative treatments, such as vacuum erection devices, intraurethral or intracavernous alprostadil, shockwave therapy, and prosthesis implantation, can help patients who do not respond to pharmacotherapeutic options.
Endothelial cells, cavernous smooth muscle, cavernosal nerve, and nitric oxide levels in the corpora cavernosa play the most important roles in normal erectile function. Approximately 80% of ED has organic causes, according to the literature. The most common organic causes of ED are vascular abnormalities, especially cavernosal veno-occlusive dysfunction, which accounts for 67%–75% of cases of ED cases, venous leakage, and aging.
Cell therapy is a promising field of research in regenerative medicine. Several stem cell studies in animals have focused on the treatment of diabetes, aging, cavernous nerve injury, and Peyronie's disease-induced ED. Stem cells can differentiate into new cells and produce growth factors through paracrine effects. These effects could improve the function of cavernosal smooth muscle cells (CSMCs), repair damaged nerves, and normalize nitric oxide levels. However, autologous stem-cell transplantation could increase the risk for the development of neoplasms.
For decades, various branches of medicine have used autologous platelet-rich plasma (PRP). Autologous PRP contains platelet concentrations that exceed physiological standards by threefold to sevenfold, which is rich in growth factors, chemokines, and angiogenic factors. For decades, various branches of medicine have used autologous platelet rich plasma (PRP) as a therapeutic agent to enhance the recovery of damaged tissue, emphasizing regulating inflammation and promoting tissue regeneration. The PRP also plays a crucial role in the regeneration of nerve cells, myelination of axons, homing and migration of progenitor cells, and prevents fibrosis and apoptosis of damaged cavernous nerve cells in corporal tissues. Autologous PRP is reportedly safe and effective in promoting wound healing, soft tissue reconstruction, bone reconstruction, and augmentation by releasing several growth factors, including platelet-derived growth factor, transforming growth factor-beta, fibroblast growth factor, insulin-like growth factors 1 and 2, vascular endothelial growth factor, and epidermal interleukin-8, keratinocyte growth factor, and connective tissue growth factor. Autologous PRP is a novel potential therapy for the restoration of erectile function.
Despite the recent application of intracavernosal PRP in clinical practice, clinical evidence in the available literature reviews remains scarce. Therefore, we conducted a prospective study to investigate the safety and efficacy of intracavernosal PRP injection in patients with ED.
| Materials and Methods|| |
Study design and participants
A single-arm prospective study was performed at a single regional teaching hospital. The study included heterosexual men 30–75 years of age diagnosed with ED more than 6 months earlier and who did not respond to conservative treatment to achieve desired therapeutic outcomes. The study excluded patients who had previously received androgen deprivation therapy, had a history of penile surgery or penile disorders, such as priapism or Peyronie's disease, or had a severe systemic disease or local skin infection. Participants with hypogonadism who received testosterone replacement therapy (TRT) or were prescribed PDE5 inhibitors could continue treatment during the study period. However, they could not change their dosage and treatment frequency of TRT or PDE5 inhibitors during the study period. All participants were initially evaluated to ascertain their comprehensive medical and sexual history.
Each participant received a penile injection of PRP every 3 weeks three times. Participants were assessed with the International Index of Erectile Function-5 (IIEF-5) scores, Erectile Hardness Score (EHS), Sexual Encounter Profiles 2 and 3 (SEP2 and SEP3), and Global Assessment Questionnaire 1 (GAQ1) at baseline and 2 weeks after each injection session. Before injection therapy, all participants were informed of the effectiveness and possible complications of treatment.
The primary objective was to assess the safety of intracavernous PRP therapy. Any adverse events were recorded. The secondary objective was to evaluate the effects of PRP injection on sexual function. Our institutional ethics committee approved the study (CTH-106-2-1-072), and all participants provided written informed consent.
Intervention and platelet-rich plasma intervention
During each intervention, 30 mL of peripheral blood was drawn from all patients. Pure PRP was prepared by the double spinning technique at 500 G and 1500 G for 15 min. Three blood product components were obtained: the first layer, consisting of platelet poor plasma; the second layer, containing PRP; and the third layer, containing white blood cells. We obtained 1–2 mL of PRP from the second layer and drew it into the syringe for later use. One urologist administered intracavernous injections to all patients through a 27-gauge needle in accordance with a sterile protocol. The injection was delivered into the corpus cavernosum; equal volumes were administered at bilateral sites of the penile shaft.
We used the Statistical Package for the Social Sciences for Windows (SPSS) version 22.0 (IBM Corporation, Armonk, NY, USA) to perform statistical analyses. Data were calculated as means ± standard deviations or as percentages. Repeated-measures analyses of variance analyzed the IIEF-5 and EHS outcomes. We used Cochran's Q-test to compare data for dichotomous dependent variables. P < 0.05 was considered statistically significant.
| Results|| |
Primary and secondary outcomes
The thirty participants were between 35 and 74 years of age, with a mean of 54.93 ± 8.31 years. The duration of ED had been approximately 25.74 months. One participant dropped out of this study after two sessions of therapy because the treatment was ineffective. [Table 1] lists the baseline characteristics of the thirty participants. No cases of hematoma, signs of infection, or pain were noted after PRP treatments were completed. Two participants reported a small induration at the injection site after the first injection, but both also reported no hindrances in sexual intercourse. ED improvement was assessed according to the IIEF-5 score, EHS, SEP2, SEP3, and GAQ1. The mean IIEF-5 score at the start of the study was 12.034 ± 5.10 and increased to 16.59 ± 5.5 after treatment was completed (P < 0.001; 95% confidence interval, 3.130–5.973) [Figure 1]. Moderate-to-severe ED was recorded in 17 patients (57%) initially and 6 (20%) after treatment. The EHS scores increased significantly by an average of 0.72 [P < 0.001; 95% confidence interval = 0.457–0.991; [Table 2]. Furthermore, in four participants who had previously reported inability to achieve an erection, good rigidity for penetration was achieved after PRP treatment, according to the SEP2 [Figure 2]a. EHS at baseline was significantly different from EHS after three treatment sessions (P = 0.028); 24 participants (80%) reported that the erection was hard enough for a satisfactory sexual experience. Only nine participants had reported “yes” on the SEP3 at the beginning of the study [P < 0.001; [Figure 2]b]. Of the 30 participants, 24 agreed that PRP treatment improved erections [Figure 2]c.
|Table 2: Changes in sexual function scores after intracavernous injection of platelet-rich plasma|
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|Figure 1: A trend of improving International Index of Erectile Function(a) and Erectile Hardness Score(b) scores as the number of injections increase|
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|Figure 2: (a) Positive response rate to the Sexual Encounter Profile-2 question “Were you able to insert penis into partner's vagina?” at the baseline and after first, second and third PRP treatments session are 76%, 86%, 86%, and 89% respectively. Cochrane's Q test indicates significant differences among baseline and after third session of treatment (Cochran's Q = 9, P = 0.029). (b) Positive response rate to the Sexual Encounter Profile-3 question “Do you have the ability to achieve successful intercourse?” are 31%, 55%, 69%, and 82% accordingly. (c) 83% participants suggested platelet rich plasma treatment is effective in Global Assessment Questionnaire-1|
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| Discussion|| |
ED is a sexual disorder that is common among men after the fifth decade of life. The causes of ED include various organic problems related to arterial–venous insufficiency and to endocrine, neurogenic, and psychological conditions. No current treatment regimens are curative or can be administered in a single session for all patients. This study included participants with ED due to varying causes. Some of them had received high-intensity focused ultrasound treatments and laparoscopic radical prostatectomy for prostate cancer. Only one participant discontinued the study after completing two sessions of PRP treatment because it was ineffective; he had reported an IIEF-5 score of 0 and an EHS score of 2 at baseline, which were unchanged after two sessions of therapy. Two participants reported small indurations at the injection site after the first injection. Although penile fibrosis may be a complication of intracavernosal therapy, the incidence ranged from 0.76% to 2.1% in a previous study; both patients who reported indurations reported no hindrances in sexual intercourse and no further progression of the indurations. No intervention was required for adverse events during the study period. For all patients who completed three sessions of intracavernous PRP injection within 9 weeks, the IIEF-5, EHS, SEP2, SEP3, and GAQ1 results improved significantly. Initially, no participant reported an EHS score of 4; however, at treatment completion, 9 of the remaining 29 patients achieved full rigidity and complete hardness. Satisfaction was reflected in self-reported performance according to the SEP2, SEP3, and GAQ1 after 9 weeks of treatment. Overall, 24 of the 30 patients indicated that PRP treatment was highly efficacious.
The causes of ED might be multifactorial and become more prevalent with age. Testosterone deficiency plays a role in ED. Hypogonadism contributes to decreased libido and vascular endothelial dysfunction due to a decrease in elastic fibers of the tunica albuginea and smooth muscle in the corpus cavernosum, which is responsible for poor erections reduced compliance with medication regimens. Furthermore, aging increases oxidative stress, which leads to endothelial dysfunction and CSMC apoptosis. Dysfunction of CSMCs causes poor relaxation of the sinusoidal smooth muscle. Apart from apoptosis, an animal study revealed that inducible nitric oxide synthase immunoreactivity was stimulated under oxidative stress promoted by macrophages and Kupffer cells, which resulted in a high concentration of nitric oxide, which in turn caused cell injury. PDE5 is a phosphodiesterase found predominantly in CSMCs, which degrade cyclic guanosine monophosphate (cGMP) into guanosine-5'-monophosphate. Thus, PDE5 inhibitors decrease the degradation of cGMP, thereby enhancing the effects of nitric oxide and augmenting relaxation of CSMCs and leading to vasocongestion. Of interest is that 60%–65% of men with ED respond to PDE5 inhibitors initially, whereas 30%–40% of patients experience treatment failure. McMahon et al. suggested that underlying reasons for the failure of PDE5 inhibitor treatment include worsening of endothelial dysfunction, the progression of atherosclerosis, and the development of tachyphylaxis.
PRP therapy has become popular in regenerative medicine and other specialties since the earliest reports of its clinical use in the 1980s and 1990s; it has been applied in cardiology, dentistry, dermatology, and maxillofacial surgery. Applications of PRP in the medical field have gained rapid momentum in recent decades because of their potential benefits and influence on repairing injured tissue. In various growth factors, activated platelets can promote regeneration and facilitate tissue renewal and repair. Growth factors can be administered conveniently and noninvasively, are inexpensive, and produced few adverse effects; therefore, they are of great interest in the field of ED therapy because they may promote tissue regeneration, as well as healing. Growth factors stimulate tissue repair mechanisms, including chemotaxis, cell proliferation, and angiogenesis; hence, PRP treatment aims to restore blood flow and stabilize the composition of the extracellular matrix and CSMCs.
Moreland demonstrated an association between corporal smooth muscle atrophy and connective tissue degeneration in the pathophysiology of ED. PRP promotes the possible recovery of erectile function by regulating inflammation and promoting recovery. To the best of our knowledge, randomized controlled clinical investigations of PRP application in human ED are lacking, although several animal studies have revealed that PRP facilitates ED recovery. Wu et al. and Ding et al. demonstrated neuroprotective and neuromodulatory effects of PRP, accompanied by decreased fibrosis and increased myelinated axons, in a cavernous nerve injury rat model. Moreover, Ding et al. suggested that growth factors and platelet gel in PRP positively affect CSMC regeneration and functional recovery.
The limitation of these two studies was that they were animal investigations. To date, limited evidence supports the use of PRP in human ED. Matz et al. reviewed a series of patients receiving PRP treatment for urological issues, which appeared to be safe and well-tolerated in patients with ED, stress urinary incontinence, and Peyronie's disease. They found that in patients with ED, the average improvement in IIEF-5 score was approximately 4.14 points, which was quite similar to our finding. In another randomized controlled trial in humans, Epifanova et al. suggested that the mechanism of erectile function recovery after autologous PRP therapy could be attributed to the active substances in autologous PRP.
To the best of our knowledge, our investigation is one of only a few prospective studies of PRP applied in human ED. Despite the small sample size, we observed no significant adverse events. Most patients tolerated the PRP injection well, completing the course of three injections. Sexual performance tended to improve significantly during the period after injection. In most participants, PRP was effective and safe. However, proper protocols for PRP preparation and injection remain unknown. Because the data are limited, randomized controlled trials and clinical studies are warranted to determine the therapeutic effect of PRP before it is accepted as standard treatment. Based on our preliminary results, we believe that intracavernous PRP injection is a safe treatment for ED.
This study was limited by the small number of participants, a sham control group, and a short follow-up period. In addition, our results included only patient-reported outcomes. Several important factors such as treatment templates and protocols, the dosage of PRP, treatment interval, and long-term success are still unclear. Further basic research is necessary to explore the long-term efficacy and safety with intracavernosal administration of PRP.
| Conclusions|| |
This pilot single-arm prospective study demonstrated that intracavernous sessional PRP injection is safe and feasible. The preliminary results indicated that this therapy produced the recovery of erectile function.
The authors would like to thank all who contributed to this study. We would like to thank two anonymous reviewers and the editor for their comments.
Financial support and sponsorship
The work was supported by the Research Support Scheme of the Cardinal Tien Hospital (CTH106A-2B04), and research projects of the Ministry of Science and Technology, R.O.C (109-2628-B-567-001, 108-2628-B-567-001, and 107-2314-B-567-001).
Conflicts of interest
Prof. Chun-Hou Liao, an editorial board member at Urological Science, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]