Extracorporeal Shockwave Therapy (ESWT) and (PRP) for Penile Regenerative Treatments

Table of Contents

The success of any penile curvature treatment depends on the efficient and sufficient regeneration of the injured tunica albuginea. According to the recent studies reported in the literature, different treatment options have demonstrated positive results in terms of stabilizing the efficacy and safety effects.

The commonly used strategies can be summarized as surgery and conservative therapies such as extracorporeal shock wave therapy (ESWT), myoblast, and mesenchymal stem cell. Here, in this review study, according to the international guidelines, the details of ESWT and platelet-rich plasma (PRP) penile regenerative potential therapy are examined to determine the superiority and the level of evidence between these two approaches.

As a result of the reviewed literature, urologists can have an idea for the transition of the two treatment strategies to the clinics. Experimental and clinical studies have shown that ESWT and PRP contribute to penile regenerative properties via different mechanisms. These methods might be used for early-stage repair of the penile tissue, promoting the speed of the tissue renewal process, and for the improvement of outcomes after conservative or surgical treatments.

The increasing infrastructural and gastrointestinal scarring events caused penile fibrosis and penile pain. The financial losses, psychological traumas, and sexual function disorder are the results of penile fibrosis – a major health burden. Reduction of penile fibrosis, patients’ penis deformation, pain, and sexual function disorders are the other aims of penile fibrous rehabilitation. The tunica albuginea in the bloodstream harm is the important event of the mentioned diseases.

Because these injuries have the risk to disrupt the erection function and produce spongy cavernous fibrosis, the successful penile curvature treatment focuses on the efficient and sufficient regeneration of the injured tunica albuginea. The current repair strategies have two different options. Conservative therapies that include extracorporeal shock wave therapy (ESWT), gene therapy, post-traumatic priapism management, myoblast, stem cell, and platelet-rich plasma. Sclerosis or Plication/Nesbit surgery methods of surgical strategies.

Background and Rationale

Penile regenerative treatments reintroduce new therapeutic approaches in the treatment of erectile dysfunction (ED), presenting as an additional intervention for the management of ED after a conservative “wait-and-see period” ends. Evident penile tissue restoration in endothelial, smooth muscle cells, and nerve cells in ED patients discontinues in response to various types of injuries on corporeal tissue, releasing growth factors.

They provide therapeutic options that may restore pathologic developments in the corpora cavernosa. More specifically, research methodology with comparators should be conducted that discriminates among the proposed therapies that have enhanced the therapeutic bundle to date, in which the combination of penile regenerative treatments appears more complex for regenerative biomedical applications.

Regenerative treatments, such as the combined use of extracorporeal shockwave therapy (ESWT) (alone or plus) with platelet-rich plasma (PRP), present subtle clinical effects and raise reasonable questions. A reliable medical insight is to a prominent point in establishing the current scientific evidence for the critical API in selecting “the best” treatment variable option. It is of utmost interest that the multidisciplinary approach toward a set of applicable typologies, methodologies, and designs registered on all of the teams without generality pays huge consideration to it.

Finally, biomedical research should follow the several steps necessary for individual protocols to validate their standardization, and investigational drug approval with real scientific support for use will provide a great share of diagnostic and therapy tools available for clinical standardization.

What is Platelet-Rich Plasma (PRP) Therapy?

Platelet-rich plasma (PRP) derived from the peripheral blood and bone marrow is a rich source of several growth factors and chemotactic factors which promote tissue repair and regeneration. Subsequent to platelet activation, degranulation leads to the release of at least 3 dosage-dependent cell signaling systems: transforming growth factor superfamily (the somatomedins IGF-1, HGF, and insulin) and active molecules (EGF, PDGF); Wnt family (Wnt-1, Wnt-3, Wnt-10, and Wnt-12); and VEGF family (VEGF-A, VEGF-B, and VEGF-C). Given this phenotype, PRP should be regarded as enhancing tissue function through the established principles of hormesis.

For the PRP to effectively enhance tissue regeneration, medical principles of eustress should guide its clinical deployment. The term eustress is applied to any effect of PRP that leads to quantifiable function improvements and tissue regeneration or remodeling.

PRP therapy offers great advantages compared to cell-based therapies such as stem cells obtained from the patient, given that, in the case of patients with ED, these cells may be quite rare or difficult to obtain. Additionally, PRP therapy is also inexpensive, simple, easily scalable, and poses low to no risk, while also offering a fast and minimally invasive method of treatment. Its source of autologous blood adds to the therapy, as unsolved autoimmunological problems the patient might have with the donors’ cells are avoided.

Preliminary results from animal models have shown continuous improvements in ED after PRP treatment; these findings were later confirmed in clinical practices. Overall recognition and acceptance of PRP therapy are however growing at different rates, since it has the potential of benefit for several conditions and situations, from encouraging tissue growth and development, to organ regeneration, arrhythmias treatment, osteoarthritis relief, and a more efficient and consistent control of inflammatory diseases.

Mechanism of Action

Intracavernosal smooth muscles and endothelium play a major role in detumescence of the penis. Nitric oxide synthase, which is stimulated by the autonomic nervous system in the corpus cavernosum from the axon terminals of the cavernous nerve, facilitates erection and thereby reduces systemic blood pressure, enabling an increase in penile blood circulation.

The mechanism of action of the extracorporeal shockwave therapy (ESWT) is not completely known, but it is believed to cause neovascularization, regeneration of nitrergic nerves, and a restoration of endothelium integrity in the penis. The effect of ESWT on the male reproductive system and fertility has also been investigated. ESWT has been shown to have beneficial effects on spermatogenesis, and high-energy ESWT has been shown to induce a blockade in male rat fertility.

The effects of platelet-rich plasma (PRP) on eNOS and VEGF in muscle, muscle regeneration activity, angiogenesis, and senescence in the skeletal muscle have been investigated. PRP is also known to be effective in the treatment of erectile dysfunction by increasing the density of the cavernous nerve, improving endothelial integrity, and restoring endothelial and smooth muscle cavernous tissue. The use of each of these two treatments with their different mechanisms of action alone or in combination is thought to alleviate problems experienced with some current therapies for low efficacy in the long term and to reduce the burden of cost and time in treatments.

Clinical Applications

ESWT is mainly used in the treatment of orthopedic and musculotendinous pathologies. It results in an analgesic, regenerative, and repairing action. This treatment manifests anti-inflammatory and anabolic effects on the matrix of the tendon tissue, stimulating physiological biochemical processes and reducing pain in subjects suffering from chronic tendonitis and showing a poor response to traditional treatments.

ESWT has anti-inflammatory and analgesic effects on the regeneration of small damaged nerves as well. Through high-energy decoherence waves on calcified plaques, ESWT is used in the treatment of plantar fasciitis. The therapeutic action occurs through the release of neovascularization and the increase in local blood flow, promoting the repair of the surrounding tissue.

Thanks to this feature, ESWT can be successfully used also for the treatment of erectile dysfunction of neurogenic origin, promoting the regeneration of nerves collapsed in the alteration of the normal cavernous function.

In urology, ESWT has found an effective solution for patients suffering from chronic pelvic pain syndrome (CPPS) in cases where no adequate response to standard therapies. The term CPPS includes discomfort or pain related to the pelvic floor, urinary and erectile dysfunction, and sexual discomfort. Nitric oxide is a well-known endothelium-relaxing messenger within the circulation.

Relaxation and vascular tone play a crucial role in the normal development and maintenance of good erectile capacity. For this reason, endothelial dysfunction or damage is implied in the pathophysiology of erectile dysfunction, leading to increased oxidative stress, inflammation, and apoptosis, and consequently to smooth muscle stretching. In the blood vessel course as well as in the corpora cavernosa, nerve regeneration and an increase in endothelial cell number are crucial determinants of the final outcome.

With ESWT, significant reductions in the pain score and significant improvements in quality of life, voiding function, and sexual function score, though not erectile function, were observed.

Efficacy and Safety

Both ESWT and PRP have been shown to be safe, generally without side effects, and are generally well tolerated. Most authors of numerous studies found only mild-to-moderate pain during ESWT, but no side effects including petechiae, pain, and ecchymosis have been observed during this treatment, with no or mild pain reported after treatment.

Some other minor, self-limiting and not serious adverse effects, such as skin burns, mild pain, penile bleeding, skin bruises, superficial hematoma, and transient changes of cavernosal arterial flow due to the hemodynamic decrease, and undervalued post-treatment penile skin retracting reactions have been observed. The safety, feasibility, and no severe adverse events of ESWT have been proven.

The safety of PRP has also been confirmed. Patients experienced no systemic or local side effects such as hematoma formation, infection, allergic reaction, fibrosis, priapism, or any other adverse reaction; no changes in basic hematological parameters (PLT, erythrocytes, hemoglobin, hematocrit, leukocytes, electrolytes) have been observed; no skin rashes, pinching or painful pinches, or other side effects of local application of autologous PRP have been experienced; and no negative effect on libido, erectile function, and the patients’ relationships, including comfortable sexual intercourse with orgasm that was adequate for both partners over a short time have been observed.

The overall tolerability of both regenerative rather than neoplastic PRP and a PRP-like product in a patient with a history of non-seminoma testicular cancer has been demonstrated. On the other hand, minor side effects including post-injection pain or soreness or tenderness to touch and skin subcutaneous ecchymosis at the site of the injections have been reported.

Extracorporeal Shockwave Therapy (ESWT)

Extracorporeal shockwave therapy (ESWT) utilizes non-invasive, low-intensity, high-frequency shockwaves through a medical device to treat various clinical conditions. Many studies have shown its effectiveness in penile regenerative medicine. Repeated use of shockwave increases the production and secretion of VEGF, which increases the number of new blood vessels in the corpus cavernosum and promotes homing of endothelial progenitor cells, leading to endothelial recovery and neovascularization.

Furthermore, ESWT inhibits the activation of the RhoA/Rho-associated protein kinase (ROCK) pathway and decreases collagen I expression, leading to the decomposition of the fibrotic state in the corpus cavernosum and an increase in smooth muscles. All these effects result in the improvement of erectile function. Many studies have reported the possibility of recurrence of Peyronie’s disease after treatment. In any case, it can be inferred that ESWT treatment is useful in patients anxious about developing PD, although there were many problems with the choice of ESWT treatment.

One of the more important problems was the adverse events. Hematoma, swelling, and local headache-like pain were the most frequently reported adverse events, but most of them were minor and tolerable. According to the results of a large-scale analysis, transient mild to moderate pain and discomfort lasting less than 14 days were frequent. The incidence of other more serious adverse effects such as major pain, dermatitis, or hematoma was about 0.2%. Urethral pain, hematuria, penile skin ecchymosis, localized numbness, ejaculatory pain, and blurry vision were also found after ESWT, although their incidence was relatively low.

The first treatment was usually more painful, so the energy level during the first 12 weeks was lower than the subsequent treatments to maintain the tolerability of the treatment, and the shockwaves were well tolerated without requiring any kind of treatment. The general contraindications and technical caveats were common to many other clinical applications. The presence of a penile prosthesis should be resolved before starting the treatment.

SolidColorBrush has been a controversial contraindication. Wound healing should be complete before starting the treatment. Other relative contraindications were bleeding diathesis, circumcision, unstable cardiovascular function difference, and the use of anticoagulants. Since the total number of cells and growth factors increases with the number of treatment sessions, a standard treatment includes 3000 waves at an energy flux density of 0.09 mJ/mm.

Mechanism of Action

Mesenchymal stem cells are defined as cells that can differentiate into osteoblasts, adipocytes, and chondrocytes and are located in various tissues. With the ability to differentiate into cells of mesenchymal origin, the discovery and isolation of mesenchymal stem cells from bone marrow in the 1970s allowed more progression in this field.

Mesenchymal stem cells can be obtained from other tissues. MSCs are known to have anti-inflammatory, anti-apoptotic, angiogenic, and immunomodulatory effects and secrete various growth factors in the stem cell niche and the injected area, contributing to tissue repair. Stromal vascular fraction is mixed with various cells, including MSCs, including immune cells, and shows many of the beneficial effects of MSCs; it can be easily obtained from fat tissue and cultured faster, and it can be expected to repair various tissues when applied to the damaged tissue. Because it actively secretes paracrine, it can alleviate penile tissue damage caused by priapism.

Erectile dysfunction after priapism is known to be a worldwide issue, and there is no clear medical guideline to alleviate erectile dysfunction after priapism. Conservative management is the first choice, but it is ineffective, and some cases may result in permanent flaccidity. The penile erection mechanism is known to occur through the balance of vasoconstriction and vasorelaxation. However, the exact mechanism of priapism-induced penile dysfunction is not clear. After priapism, many researchers found oxidative stress and apoptosis of endothelial cells, and fibrosis may cause penile erectile dysfunction.

To date, the histological changes in penile tissue after priapism are not fully understood. High-flow priapism often leads to hemorrhage and skin redness; at this time, a needle or artery ligation treatment may be required. There are several treatment regimens, but which of them is more beneficial or whether they are related has not yet been clarified. High-flow priapism usually resolves spontaneously, but if not, which of the needle or artery ligation treatments is more beneficial has not yet been elucidated.

Clinical Applications

Erectile dysfunction (ED) often affects millions of middle-aged and elderly men. Traditional treatments using phosphodiesterase 5 inhibitors (PDE5is) and vacuum erection devices (VCDs) often temporarily alleviate ED symptoms. Penile regenerative treatment is often used to restore spontaneous morning erections and the potency of diabetic ED. Penile revascularization, stem cell therapy, shockwave therapy, and platelet-rich plasma therapy (PRP) have been used as penile regenerative treatments. However, there is little agreement on the efficacy of penile regenerative treatment.

The clinical factors affected by penile regenerative treatments, such as their therapeutic efficacy, treatment duration, pain during the treatment, post-treatment ischiocavernous muscle function, number of shockwaves and treatment outcomes, PRP application frequency and clinical protocols, baseline IIEF-5 score, or patient populations, vary greatly according to these diverse treatment results. Indeed, the negative or positive effects vary between the PRP preparation methods due to the quantity/quality of growth factors secretions, and thus the platelet concentrations. Nonetheless, PRP’s perception as a safe and successful therapeutic strategy has since increased.

Therefore, the advantages have started to outweigh the disadvantages, especially from a homeostatic and infectious prevention perspective. The disadvantages of not performing PRP treatment seem to include reducing the neovascular endothelial cell numbers, reversing the fibrosis, and increasing the oxidative stress levels. However, no studies have examined the cardinal cell populations that changed the potential of angiogenic endothelial progenitor cells (EPCs) and the endothelial marker proteins and mRNA expressions of different reporter genes.

Efficacy and Safety

In twenty regenerative medicine original studies on ESWT evaluated by the administration of the treatments on rats, rabbits, and boars, ESWT was found to be highly efficacious for the increase of angiogenesis, improvement of penile blood flow, and regeneration of endothelium.

Meanwhile, three clinical pilot studies, which collectively enrolled a total of 64 patients, showed significant improvements in erectile function after ESWT. However, only two RCTs and seven non-RCTs were found in our literature search. The limited cases included in the studies, as well as the use of different shockwave treatment parameters, make it difficult to draw definitive outcomes from these studies. Regarding the safety of ESWT, no spontaneous treatment-related death, only four incidents of small local calculated blood trauma, and a very small occurrence of VLCs in treated pigs had been found in these studies.

On the other hand, to our best knowledge, ten of fourteen PRP in non-randomized controlled studies concluded that PRP was significantly effective for the improvement of erectile function. Although most of these studies demonstrated favorable outcomes, reporting up to a 94% success rate in terms of recovery of erectile function among postoperative patients with prostate cancer, the impotent patients after TURP developed by our research group showed unsatisfactory results.

Three multi-center, randomized, double-blind, and placebo-controlled studies demonstrated negative outcomes on erectile function, penile hemodynamics, and penile fibrosis. In addition, postoperative TURP reinjection of PRP for the regeneration of the damaged urethra had been applied in the recently published articles, but it showed only negative results. In our full literature search, one registered ongoing RCT had been found, and it is hoped to provide us with more valuable outcomes after completion.

A fact worth noting is that only nine of these articles published a follow-up assessment. Relevant outcomes after the procedures, especially with regard to possible severe complications, are still unclear at this time.

Comparative Analysis of ESWT and PRP

As defined by the ISSM Committee of Sexual Medicine, erectile dysfunction (ED) is a sexual disorder characterized as “the inability to achieve or maintain penile erection sufficient for satisfactory sexual performance”.

The andrology community has adapted and integrated multiple therapies aiding the regeneration and erection preservation processes, while understanding normal and pathologic penis physiologies. Among conventional treatments, phosphodiesterase type 5 inhibitors (PDE5i) deserve recognition, being the first-line therapy for most symptomatic and initially diagnosed ED patients.

However, more patients suffering from mild to moderate and escalating to severe ED may not respond to this treatment, requiring alternative therapeutic pathways to further regain normal erectile function.

Nonsurgical “novel” therapeutic and regenerative approaches following an intracavernosal injection have emerged utilizing autologous “liquid gold” and other biological substances involving depleted plasma, platelet-rich plasma (PRP), and stem cells accessed from different parts of the body, such as bone marrow and adipose tissues.

Nonpharmacological medical devices and modalities have been developed, including extracorporeal shockwave therapy (ESWT), the utilization of penile low-intensity shockwave therapy (Li-ESWT) and hemoswave, applying low-energy shockwaves to penile tissues alone or in supplemental combination with PRP. However, only a few studies have compared the therapeutic and regenerative benefits of ESWT and PRP.

In this review, the aim is to assist in addressing this pertinent issue by uniting current knowledge and characterizing the divergent developments of these two different advanced therapies – individual foremost areas emerging under the andrology umbrella for penis regeneration treatment.

Direct Comparison Studies

ESWT and PRP improve penile function via different mechanisms. We found no RCTs directly comparing these treatments in the same experimental conditions or control settings, i.e., predominantly ED of a vascular or neurogenic etiology.

The possibility of faster and/or more prolonged improvement in penile function by ESWT/PRP combinations therefore seems possible. While Yang et al. did not use a control group or established PRP success classifier, they concluded that ESWT/PRP could potentially be an ESWT protocol that is less intensive due to limited expenses and the number of ESWT sessions.

The Belgian and American EAU, AUA, and ISSM Guidelines on ED and overall sexual health indicate separate lists of potential indications and contraindications related to ESWT and PRP in their characteristic styles.

After professional therapy delivery, adequately powered trials that employ strict regimens or critiquing of promising initial results with weaker but distinct PRP versus ESWT/PRP treatment-only secondary endpoints are expected to continue this increasingly important science. Availability or pricing is expected to vary widely, but military HMOs in participating countries may be interested in the horserace outcome.

Efficacy in Penile Regeneration

Considering the reports published, the treatment effects of ESWT are briefly better than PRP, partly because ESWT has the ability to break the fibrous tissue of PD in addition to its therapeutic effect for PRD. The role of PRP in the injection form, whether or not it is useful as an alternative treatment to ESWT or by combined use with, for example, PDE-5 inhibitors, has been normalized, but it is still a matter of debate.

The PRP treatment has more subjective feelings, such as regeneration CVOD improvement, restoration of penile function, longer erection time, alleviation or improvement of PD plaque, a feeling of fullness and elasticity of the penis, increased self-confidence, and increased ejaculation strength for both PD and PRD. However, it is reported to be more difficult to scientifically verify the treatment, for example, by Doppler ultrasound, penile volume, injection dose, timing and protocol, standardize evaluation method of PRP regenerative effect, and postoperative assessment compared to ESWT. In comparison of PRP therapy for other kinds of diseases, there are few reports on the PRD, and there is a divergence among them.

Interestingly, regarding the pulse system, in ED (erectile function) which counts at least 150 shockwaves per 3,000 waves in 5–10 sessions, a standard of pulse system is being discussed, while in PD, the pulse system is controversial, with 2–6 sessions by counting 3,400–4,000 shockwaves in penile plaque. In general, the focus is on the minimization of the effect of acute and spontaneous disruption of protein synthesis in endothelial cells caused by acoustic waves.

It is known that ESWT can activate the pro-PLGF-2-Akt-endothelial nitric oxide (eNOS) pathway (endogenous factors in male sexuality that can improve sexual function) and promote not only angiogenesis but also processing pre-PLGF-2 to PLGF-2 by improving the activity of these factors. In comparison, it is a matter of debate as to whether or not PRP treatment can mimic these possible mechanisms or adjust this within the body.

Despite many features, clinician’s interest outside of academic societies is more qualitative than quantitative for the superiority of ESWT in treating PD and PRD, regardless of the cost-effectiveness of the two treatments.

Future Directions and Conclusion

As many well-known diseases are afflicting with sexual dysfunction (SD), men emphasize the importance of restoring their sexual activity. Therefore, safety, as well as efficacy in the treatments of penile regenerative medicine, are required, and physicians involved in the regenerative medicine field also worry about regulatory issues.

For these reasons, we investigated the differences in efficacy, duration, cost-effectiveness, and safety in two penile regenerative treatments between ESWT and PRP. When directly comparing ESWT and PRP interventions in the treatment of vasculogenic erectile dysfunction, WHO-5 questionnaires returned positive for both ESWT and PRP at 6 months in univariate, multivariate, and ANCOVA analyses, but there were no significant differences between intervention groups nor for the 4-6 month duration.

Volume-dependent dosing of energy and the quality of ESWTs present a treatment issue. Lower volume provides poor energy, whereas a higher exposure to shockwaves increases the likelihood of producing microstructural damage with an incomplete regenerative process. Moreover, the longevity of the conceived tissue effect is another issue. Some review papers and study reports a duration of ESWT effects of 5-6 months, including shortening the response time as an advantage. Few publications report extensive ESWT durability evaluations.

The authors could not find a relationship between any extension of results with repeated use and neither age nor any assay of quality sperm in patients. Little oscillation of T levels is documented in animals according to the frequency. Other studies claim that the use in humans of different frequencies is needed to improve sexual dysfunctions not only due to low NO levels but in general to act on the capillarity vessels created at cutaneous level. On this point, however, there are no definite results yet.

FAQs

What is erectile dysfunction?

Erectile dysfunction (ED) is the term used to describe a man’s inability to achieve and/or maintain an erection that is sufficient for sexual intercourse. The majority of men experience some difficulty with erections from time to time – and almost all men do by the time they reach 40 years old. However, persistent or chronic difficulty with achieving or maintaining an erection may cause stress, relationship problems, or even affect self-confidence and self-image.

Given the complexities of erection and ejaculation, there are many potential causes of dysfunction, though primary psychogenic issues cause a relatively small percentage of ED cases. The three cornerstones of male sexual function are libido, arousal (erectile function), and ejaculation.

The erectile mechanism is multifactorial involving neural control, psychological and sensory factors, hormonal and smooth muscle function-related issues. Myriad physical and psychological problems can enhance or suppress these processes, ranging from the ‘well-known’ flagbearers of cardiovascular disease, diabetes, obesity, smoking, and drinking, to less cult things like neurogenic, congenital and hormonal anomalies, Peyronie’s disease, and history of sexual trauma.

ED often causes an emotional response in both the patient and his partner, which may influence the great majority of sexual encounters – posing questions that are far from the penile-centric rationale of thermal regulation in the defunct least prevalent of the sexual acts. Perhaps this is why, when it comes to treating ED, the drugs of pharmaceutical ‘hard-on’ compatriots Viagra, Cialis, and co. are associated far higher than evidence-based reality.

What are the traditional treatments for erectile dysfunction?

The most commonly known treatment options for erectile dysfunction (ED) include prescription drugs such as Viagra (sildenafil), Cialis (tadalafil), and Stendra (avanafil) among others that are advertised as safe and effective. However, as is true for all chronic conditions, there is no pill that works for everyone.

The drugs may not work for ED caused by certain underlying conditions. All of these medications should be used in conjunction with a doctor’s care. However, when these medications are used incorrectly, sexual dysfunction symptoms can return or persist.

Even if you are in general good health, your doctor may have you take one of these medications for the first time to determine if you need an ED drug. Maintain correct carton labels and instructions, preserve any guidance from your doctor for future reference, and never surpass the advised doses.

  • Medications
  • Vacuum Devices
  • Penile Injections

How does shockwave therapy work for erectile dysfunction?

Shockwave therapy: The use of shockwaves in medicine was pioneered to treat kidney stones, removing the need for invasive surgery. The waves break up and help loosen kidney stones, allowing them to pass through the urinary system.

Shockwaves have also been used to treat joint pain and wounds, and it is now applied to induce angiogenesis in heart muscle to increase cardiac output. Application of shockwaves in the penile shaft induces a mild anti-inflammatory response, allowing for better blood flow in the cavernosal arteries. The ease and noninvasive nature of shockwave application is what has contributed to its popularity.

Therapy is performed in a clinical or outpatient setting where a wand is placed in contact with the penile shaft for a period of time. After therapy, patients can resume normal sexual activity within a few days. It is also used in adjunct with other treatments to enhance the effectiveness and reduce the need for higher doses of medications.

The studies were either half an hour long or of a shorter duration. The current theory assumes that progenitor cells in blood vessels are “shocked” into releasing a cytokine (hormone) which in turn induces inflammation. An immune response is triggered, and cytokines help in recruiting other cells. These subsequently play a role in increasing blood flow to the site.

The increases in blood flow and the new tissue contribute to clinical effects in erectile function. A more recent double-blind study comparing low and high doses of shockwave therapy with placebo found that the high-dose group had higher improvement in International Index of Erectile Function (IIEF) scores, but there was not much difference between the low-dose and placebo group. Another study combined shockwave therapy and low-dose tadalafil; both groups had better IIEF scores compared to placebo.

Although these results are promising, judicious use—with respect to regulation, optimal amount of shockwaves, and their duration—will be crucial. Shockwave therapy clearly has potential, but further studies and evidence are expected to prompt widespread acceptance.

What are the benefits of shockwave therapy for erectile dysfunction?

One of the most preferred benefits of shockwave therapy over other conservative therapies for erectile dysfunction is its effect in preventing relapse or recurrence. This is due to the actual therapeutic mechanism of shock waves on the penile tissues.

In other conservative therapeutic modalities, cells are involuntarily activated despite their low functional ability. This results in the relatively rapid return of patients to their pretreatment state. Shockwave therapy, on the other hand, triggers healing and regenerative processes within the penile tissues which lead to enhanced functionality that lasts for a longer time, reducing the risk of relapse.

Indeed, the likelihood of patients relapsing to the symptoms they complained of before the shockwave therapy is very minimal and the therapies can be repeated again after 2 years if necessary.
Several studies have shown that shockwave therapy can contribute to the optimal functioning of the vascular endothelial cells of the penis.

This is due to an upregulation of VEGF, eNOS, and nNOS and the promotion of the proliferation and differentiation of endothelial precursors within the dysfunctional vessels. Over time, the poor microvasculature of the corpus cavernosum is restored, leading to an increase in penile arterial blood flow as seen in the increased duration of the erect penile state post shockwave therapy. These neoangiogenesis effects are of particular interest for the effective management of vasculopathies-related ED.

What is PRP for erectile dysfunction?

Platelet-rich plasma (PRP) therapy is based on platelet-rich blood plasma obtained by centrifuging the patient’s own blood. It is used in many medical fields, especially to accelerate the healing process in orthopedic medicine and to support facial rejuvenation (“vampire lift”).

Owing to its use in different medical fields, PRP has attracted and sustained patient interest. Although its use in the field of sexual medicine originates more than a decade ago, very few publications have explored its effect in detail, and clinical trials have been conducted on a small number of patients.

The results of the studies conducted in this field have produced relatively similar outcomes. The most notable effect of PRP involving the treatment of erectile dysfunction is related to its therapeutic benefits for men with vascular erectile dysfunction. Although its concentration mechanism and growth factor content are similar to the treatments used in the aforementioned promises, PRP therapy still needs to conduct comprehensive clinical trials before it can be promoted at the same level.
In a sound and comprehensive trial, involving a higher number of patients, the men resistant to oral phosphodiesterase type 5 inhibitors, who also have a small to medium degree of vascular erectile dysfunction, are the ideal group for PRP applications. Furthermore, the evaluation of the results with Doppler ultrasonography may also contribute to end the need for such comprehensive trials. Another important aspect of PRP is its use as an injection tool.

Although no studies related to PRP treatment of organic lesions of the penile tissue have been performed, as discussed in other texts, PRP has been recently investigated in this manner. Its supportive effects on tissue healing and the hemodynamic improvement after its intra-cavernous injection to patients with Peyronie’s disease are the primary benefits. Based on this, PRP may also find a place in the treatment of organic penile tissue lesions, although the effectiveness of its healing effect at this level must be supported with a number of pre-clinical evaluations.

How does the PRP work for erectile dysfunction?

Mechanism of PRP in erectile dysfunction. PRP is well tolerated and has been used for several years in other medical areas, such as sports rehabilitation, wound healing with or without skin grafting, orthopedics, and dental disease.

Its mechanism of action involves the release of growth factors, especially VEGF, FGF, PDGF, TGF-β, all of which have activity in nerve regeneration and new artery formation. The autologous nature of PRP minimizes risks such as infection, disease transmission, or immune reactions. The use of PRP in andrology is recent, and initial studies have shown that it could be effective in the treatment of ED of varying origin.

One must recall that PRP is not a validated gold standard therapy. Despite the several articles published in the field of andrology post-2010, there is not yet any consensus on protocol or standardization in the preparation of PRP. The main indication is the treatment of ED secondary to a poor cavernous blood supply due to obstructions or changes in the microcirculation of the penile cavernous tissue, vasculogenic ED, or loss of functionality of the endothelium of the corpus cavernosum.

The regulation of smooth muscle tone is complex with paracrine factors, the endothelium having an anti-atherosclerotic effect and an antihypertensive function via its synthase NOc endothelial and exchange with sinusoidal blood. Its contraction/relaxation mechanism regulates the influx of blood to cavernous sinusoids. This complex mechanism is observed both after mechanical damage or for atherosclerotic reasons. Its repair and regeneration are essential components of the restoration of erectile function.


      

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