Erectile Dysfunctions

New Generation Regenerative Erectile Dysfunction (ED) Treatments

In recent years, new generation regenerative treatments for erectile dysfunction (erection problems) such as low-intensity shock wave therapy (ESWT), exosome therapies, stromal vascular fraction (SVF) stem cell therapy, and PRP applications have come to the fore. These methods are based on the use of growth factors that stimulate neovascularization and the repair process in penile tissue.

According to recent studies, ESWT can provide significant improvement in individuals with mild and moderate erectile dysfunction. On the other hand, clinical evidence for PRP and stem cell applications is weak and mostly at the experimental level. While the Turkish Andrology Association and European Association of Urology (EAU) guidelines still consider stem cell and PRP treatments as emerging methods, they state that ESWT therapy is an option that can be applied with physician evaluation, especially in patients with mild erectile dysfunction. Therefore, ESWT stands out as a modern and supportive treatment option that can be evaluated with personalized planning in the appropriate patient group.

What is Low-Intensity Shock Wave Therapy (ESWT, SWT) and How is it Applied?

Low-intensity shock wave therapy (ESWT) is a method that activates repair processes by creating microtraumas through acoustic sound waves applied externally to the penis tissue. Shock waves are applied to different areas of the penis, aiming to support the entire tissue equally. As a result of these microtraumas, the body secretes endogenous growth factors, providing new blood vessel formation (angiogenesis) and increased blood supply to the penile tissue. ESWT treatment helps the natural erection mechanism work better by supporting blood circulation and nerve impulses in the penis. The procedure is generally painless and does not require anesthesia.

In individuals with mild-to-moderate erectile dysfunction, it is usually programmed as two to three sessions per week, with a minimum of 6 sessions. In more severe cases of the disease, this number of sessions can be increased to 12 or even 18. In each session, shock waves are applied for approximately 15 minutes to the base and head area of the penis with an applicator applied with gel lubricant. Anesthesia is not necessary; patients tolerate the treatment as painless, except for slight discomfort. Treatment protocols vary in terms of device, wave intensity, number of pulses, and week intervals.

In many scientific studies conducted on ESWT treatment, an average increase of 3–4 points in patients' performance scores has been observed. Additionally, a significant improvement in hardness quality has been reported in a large portion of those treated. It is reported that the ESWT effect generally appears within 1–3 months following treatment and decreases within 2–5 years.

ESWT is a very safe application. According to clinical series, no serious side effects have been reported. Rarely, redness, edema, or small subcutaneous bleeding may be seen on the penis skin (it resolves with cold compress). Slight bleeding from the urethra has been reported rarely and generally heals spontaneously. In summary, compared to other erectile dysfunction treatments, its side effects are almost non-existent.

For Whom is Low-Intensity Shock Wave Therapy (ESWT, SWT) Not Suitable?

• •Active infection or inflammation (urethritis, prostatitis, etc.)
• •Open injury or dermatitis on the penis
• •Very advanced vascular stiffness, history of penile infarction
• •Presence of coagulopathy or bleeding disorder (fluid restriction/bleeding risk is considered before treatment)

ESWT treatment is most effective in individuals with mild and moderate erectile dysfunction caused by vascular issues (for example, due to diabetes or blood pressure). It can be a good alternative, especially for people who partially benefit from medications but cannot get sufficient results, or who do not prefer methods such as injections or vacuums.

In cases due to neurological, hormonal, or psychological reasons, it may not be sufficient on its own. Besides, in some cases, it can be preferred in combination with other treatments to increase effectiveness.

Improvement in erectile function is usually seen within 1–3 months after ESWT; after this period, session repetition can be done according to the recommended treatment intervals (for example, supplement after 6 months). The individual should be monitored regularly with the IIEF questionnaire and palpable hardness scores after treatment. Treatment repetition can be considered if effectiveness decreases or risk factors are present.

Additionally, ESWT can be used as an alternative or combined with other treatments. For example, simultaneous use with PDE5 inhibitors has been applied along with vacuum devices or alprostadil injection. Other regenerative methods such as PRP, SVF, and Exosomes can also be combined.

Exosome Treatments in Erectile Dysfunction

Exosomes are small vesicles 30–150 nm in diameter secreted by cells. They carry intercellular signals by harboring growth factors, microRNAs, and proteins. Stem cell-derived exosomes (MSC-derived exosomes) specifically have anti-inflammatory and angiogenic action mechanisms. In the erectile dysfunction model, exosomes have been shown to stimulate endothelial cell growth, nerve healing, and reduce fibrosis in penile tissue. In other words, exosomes aim for tissue regeneration by ensuring the use of factors secreted by stem cells instead of the actual stem cells themselves.

A standard protocol for erectile dysfunction has not yet been established in the world. However, with our clinical experience, we have our own protocols for our guests. Anesthesia is not required for this procedure, or local anesthesia can be used; the injection is made into the spongy tissue of the penis, similar to PRP and stem cell injection.

While clinical data is limited, exosomes are safer compared to heterologous stem cells (immune reaction is minimal). There are no reports of systemic side effects in animal studies.

Although it is easy to apply, there is no list of contraindications (unrecommended situations); however, similar to the stem cell procedure, it should absolutely not be applied in cases of active cancer or infection. Multiple injections can be considered in an ideal protocol. In our clinical practice, we perform IIEF testing and, if necessary, penile doppler USG for follow-up.

Stem Cell Therapy in Erectile Dysfunction (Stromal Vascular Fraction, SVF)

Stromal vascular fraction (SVF) is a mixture of stem cells and support cells obtained from adipose tissue by liposuction. It contains a large number of cells such as mesenchymal stem cells, endothelium, and macrophages. These cells are given directly in situ. The mechanism of action is primarily paracrine: SVF cells aim to repair the blood vessel and nerve structure of the penis by secreting growth factors and cytokines, and to encourage smooth muscle and nerve regeneration. Studies have shown that SVF application increases penile artery and NO synthesis, and stimulates nerve and endothelial healing. Significant improvements have been seen, especially in diabetic and nerve-damaged ED (erectile dysfunction) models. The difference between SVF and PRP is the direct use of the stem cell mixture.

Abdominal or thigh fat tissue is usually taken from the person by liposuction (with local anesthesia). The obtained fat is centrifuged with sterile processing kits to separate the SVF. Then, it is injected into the penile cavernosa under local anesthesia. The procedure time can take 1 hour in total (lipo+lipo-processing+injection). Anesthesia is mostly done locally or as sedation with local; general anesthesia is rarely required. Antibiotic prophylaxis is given to the guest. In the literature and in people who benefit, repeated injections have been made at 6-month to 1-year intervals.

A recent meta-analysis (11 studies, 373 patients) reported significant improvement in IIEF and EHS scores at the end of 6 months in SVF and similar stem cell applications.

SVF injections are generally well tolerated. Common side effects include: pain at the injection site, temporary edema, or hematoma. There may also be pain and bruising in the liposuction area. Although infection, implant rejection, or autoimmune risks are negligible because it is autologous (from the patient himself) cells, the risk is low. Briefly, the safety profile is evaluated as good.

For Whom is Stem Cell Therapy in Erectile Dysfunction Not Suitable?

• •Active malignancy or history of cancer (especially prostate cancer)
• •Local/General inflammatory disease (infection, immune disorders)
• •Coagulopathy (risk of bleeding in activities and injection)
• •Infectious disease carrier (HIV, HBV, HCV; must be tested before cell processing)
• •Additionally, patients with adipose tissue too low for liposuction are not suitable

People to be included in this treatment are generally selected to be ideal candidates: men who do not respond to other treatments, especially those with organic-caused ED, whose general health status is acceptable, who do not require surgery, and whose expectations are realistic. It can be preferred for reconstructive purposes in cases such as persistent ED after prostate surgery, long-term diabetic ED, and hypogonadism.

Current data report improvement in IIEF scores measured 3–6 months after application. According to study results, the best result usually appears within 6–12 months. In follow-up, IIEF/IIEF-EF test, physical examination, and if necessary, penile color Doppler USG are recommended every 3 months. In cases where SVF alone may not be sufficient, it can be combined with other treatments. Additionally, when considered with the correction of underlying risk factors (diabetes, hypertension, hypercholesterolemia) and lifestyle changes (smoking cessation, exercise), treatment success may be higher.

PRP (P-Shot) Treatment in Erectile Dysfunction

PRP treatment is based on injecting platelet-rich plasma obtained from the patient's own blood into the penis. This method is called "P-Shot" (Priapus Shot). The platelet concentration in PRP is 3–8 times higher than in normal blood.

Growth factors such as VEGF, PDGF, EGF, and IGF-1 found in platelets stimulate wound healing, new blood vessel formation, and tissue repair. After PRP is applied, these factors are released in the target tissue; neovascularization and nerve regeneration are triggered in the cavernous tissue. Likewise, collagen synthesis increases, and a general "renewal" effect is provided to the penile tissue. Although current protocols vary, generally the following steps are followed: ~20 cc of blood is taken from the patient, this blood is processed by centrifugation method to separate 3–5 cc of PRP. The process takes ~30–45 minutes in total. The penis is numbed with topical anesthesia and the injection is applied to the penis shaft with a fine needle. In some protocols, injections are also made around the head of the penis. Sessions are usually applied 3 times, at 1–2 week intervals. In cases where sufficient benefit cannot be provided, additional sessions (at the 6th and 12th months) may be recommended. Serious anesthesia is not required, the person is awake.

There are several studies on the effectiveness of PRP treatment. According to the EAU guide, in the first RCT of 60 patients, the IIEF-EF increase exceeding the MCID threshold at the end of 6 months was found to be 69% in the PRP group (placebo 27%) and an average of +3.9 increase in the IIEF score was reported. In another study, a significant improvement in IIEF and SEP scores in favor of PRP was seen.

No serious side effect of PRP application has been reported. Since the patient's own blood is used, there is no allergic reaction or foreign body reaction. Pain, edema, or bruising lasting for a few days at the injection site (in 10–15% of cases) may be seen. In summary, it is a safe procedure.

For Whom is PRP (P-Shot) Treatment in Erectile Dysfunction Not Suitable?

• •Thrombosis/hematological disorders (thrombocytopenia, coagulation disorders): PRP may not be obtained or the risk increases
• •Active penis infection (urethritis, herpes, etc.)
• •Immunosuppressive diseases or cancer

PRP is generally applied in mild–moderate organic erection problems. In severe psychogenic or medical cases, it may not be sufficient on its own.

Improvement begins to be felt within 3 weeks of PRP application, and maximum effect is seen in ~3 months. Although some sources claim permanent effect, there is no long-term data. The individual is usually re-evaluated with the IIEF test weeks later. In case of insufficient effect, additional sessions can be performed. Penile Doppler USG follow-up is used limitedly.

Frequently Asked Questions (FAQ)