Erectile dysfunction (ED) is a well-known complication of radical prostatectomy (RP). Oral 5-phosphodiesterase inhibitors are currently the most widely used penile rehabilitation treatment for ED following RP, but they are less effective than for those with general ED. Low-intensity extracorporeal shock wave treatment (LI-ESWT), causing a biological change that induces neovascularization, has recently been used as a treatment for ED. Therefore, we conducted a systematic review and meta-analysis to investigate the efficiency of LI-ESWT in ED following RP. PubMed, Embase, and the Cochrane Library were searched up until December 2021. The endpoint was the change in IIEF scores after LI-ESWT. Five papers (460 patients) were included in the final analysis. In IIEF scores performed 3–4 months after LI-ESWT, the group receiving LI-ESWT showed statistically significantly better results than the control (WMD = −2.04; 95% CI, −3.72 to −0.35; p = 0.02). However, there were a total of two studies that measured the results after 9–12 months. There was no statistical difference between the two groups (WMD = −5.37; 95% CI, −12.42 to 1.69; p = 0.14). The results of this analysis indicate that LI-ESWT showed a statistically significant effect on early recovery in penile rehabilitation of ED following RP. However, the level of evidence was low. Therefore, careful interpretation of the results is required.

BackgroundThe odds of erectile dysfunction are three times more prevalent in diabetes. Severe peripheral vascular and neural damage in diabetic patients responds poorly to phosphodiesterase‐5 (PDE5) inhibitors. However, bone morphogenetic protein 2 is known to be involved in angiogenesis.ObjectivesTo assess the efficacy of bone morphogenetic protein 2 in stimulating angiogenesis and augmenting nerve regeneration in a mouse model of diabetic‐induced erectile dysfunction.Materials and methodsThe induction of diabetes mellitus was performed by streptozotocin (50 mg/kg daily) administered intraperitoneally for 5 successive days to male C57BL/6 mice that were 8 weeks old. Eight weeks post‐inductions, animals were allocated to one of five groups: a control group, a streptozotocin‐induced diabetic mouse group receiving two intracavernous 20 μL phosphate‐buffered saline injections, or one of three bone morphogenetic protein 2 groups administered two injections of bone morphogenetic protein 2 protein (1, 5, or 10 μg) diluted in 20 μL of phosphate‐buffered saline within a 3‐day interval between the first and second injections. The erectile functions were assessed 2 weeks after phosphate‐buffered saline or bone morphogenetic protein 2 protein injections by recording the intracavernous pressure through cavernous nerve electrical stimulation. Angiogenic activities and nerve regenerating effects of bone morphogenetic protein 2 were determined in penile tissues, aorta, vena cava, the main pelvic ganglions, the dorsal roots, and from the primary cultured mouse cavernous endothelial cells. Moreover, fibrosis‐related factor protein expressions were evaluated by western blotting.ResultsErectile function recovery to 81% of the control value in diabetic mice was found with intracavernous bone morphogenetic protein 2 injection (5 μg/20 μL). Pericytes and endothelial cells were extensively restored. It was confirmed that angiogenesis was promoted in the corpus cavernosum of diabetic mice treated with bone morphogenetic protein 2 through increased ex vivo sprouting of aortic rings, vena cava and penile tissues, and migration and tube formation of mouse cavernous endothelial cells. Bone morphogenetic protein 2 protein enhanced cell proliferation and reduced apoptosis in mouse cavernous endothelial cells and penile tissues, and promoted neurite outgrowth in major pelvic ganglia and dorsal root ganglia under high‐glucose conditions. Furthermore, bone morphogenetic protein 2 suppressed fibrosis by reducing mouse cavernous endothelial cell fibronectin, collagen 1, and collagen 4 levels under high‐glucose conditions.ConclusionBone morphogenetic protein 2 modulates neurovascular regeneration and inhibits fibrosis to revive the mouse erection function in diabetic conditions. Our findings propose that the bone morphogenetic protein 2 protein represents a novel and promising approach to treating diabetes‐related erectile dysfunction.