(S3) evaluation of the efficacy and safety of the penile intra-corporeal injectable regenerative therapies for erectile dysfunction: a systematic review of studies from the Middle East and North Africa (MENA) region

Abstract Background Several injectable regenerative therapies (RT) for erectile dysfunction (ED) are introduced in recent years to help patients with refractory ED not responding to pharmacotherapy including phosphodiesterase inhibitors (PDE5i) or intracorporeal injection (ICI) of vasoactive substances. These include plasma-rich platelets (PRP), botulinum toxin (BTX), and stem cells (SC) with contradictory data regarding their effectiveness as ED treatment. This systematic review aims to evaluate the efficacy and safety of injectable RT in managing ED as per clinical studies originating from the Middle East and North Africa (MENA) region. Methods A systematic review was performed using PubMed as the primary search engine. Studies were included if they evaluated the effects of any of the injectable regenerative therapies for ED including PRP, BTX and SC on patients with ED, had a prospective design, reported outcomes such as the International Index of Erectile Function (IIEF), Erection Hardness Scale (EHS), Pharmaco-penile Duplex and other relevant measures, and originated from countries within the MENA region. The review included randomized controlled trials (RCTs), non-randomized comparative, and observational studies. Results PRP Therapy: Four clinical studies (1 RCT, 3 prospective) on 252 patients (range: 34–100 per study) evaluated PRP therapy for ED. Protocols varied in session frequency (2–8 sessions) and intervals (weekly to monthly). Most studies used two-step centrifugation (5–10 minutes, 1000–3500 rpm). Two studies combined PRP with PDE5 inhibitors. PRP resulted in a 31–41% improvement in IIEF-5 scores, with two studies showing significant peak systolic velocity (PSV) and end diastolic velocity (EDV) improvements on penile Doppler. No significant adverse effects were reported. BTX Therapy: Two placebo-controlled RCTs involving 146 patients with refractory ED assessed BTX injections. The first study found significant improvements in EHS, PSV, EDV, and GAQ-1 within two weeks, with sustained gains in SHIM and SEP-2 at six and twelve weeks. The second study compared BTX dosages (50 U vs. 100 U) and showed dose-dependent improvements in SHIM, EHS, SEP-2/3, GAQ-1/2, and Doppler parameters, with longer effects (up to six months) in the 100 U group. No major side effects were observed. Stem Cell Therapy (SC): Two non-randomized studies on 26 diabetic patients with pharmacotherapy-resistant ED assessed intra-cavernous BM-MSC injections (two doses, 30 days apart). Initial improvements in EHS and IIEF-15 were observed in most patients, with plateauing effects after six months but sustained improvements over baseline at one year. Doppler studies showed improved PSV at three months. No significant adverse effects were reported. Conclusion Currently, there is not enough evidence from studies from the MENA region to approve the routine use of injectable RT for ED due to scarce data and the lack of standardized preparation and treatment protocols. However, PRP might be a promising therapeutic modality for ED patients, being the most studied treatment modality. All RT modalities are well tolerated and have a good safety profile. Therefore, large-sample RCTs with long-term follow-up are needed.