The etiologies of erectile dysfunction (ED) after nerve-sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague-Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham-operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor-beta(1) (TGF-beta(1)) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase-polymerase chain reaction. Hypoxia-inducible factor-1alpha (HIF-1alpha), TGF-beta(1), and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross-sections at 3 months was similar in both groups. TGF-beta(1) mRNA expression, HIF-1alpha, TGF-beta(1), and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF-beta(1), HIF-1alpha, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF-beta(1), HIF-1alpha, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.

Introduction The prevalence of erectile dysfunction (ED) and associated risk factors has been described in many countries, but there are still only a few studies from Asia. Aim We investigated the prevalences of ED and premature ejaculation (PE) in Korean men and the impact of general health, lifestyle, and psychosocial factors on these conditions. Methods To assess ED and PE, 1,570 Korean men aged 40–79 years were interviewed with a self-administered questionnaire on sexual function and the International Index of Erectile Function (IIEF)-5. In addition, blood chemistry was analyzed for each subject. Main Outcome Measures The prevalences of ED and PE were obtained from self-reported ED, IIEF-5 scoring, EF (erectile function) domain scoring, and self-reported intravaginal ejaculatory latency time (IELT). The data were analyzed for the presence of risk factors and the relationship of general health, lifestyle, and psychosocial factors with ED. Results The prevalences of ED among Korean men were 13.4% (self-reported ED) and 32.4% (IIEF-5 score ≤ 17), and PE prevalences were 11% (IELT ≤ 2-min) and 33.1% (IELT ≤ 5-min). ED was more prevalent in the subject groups with older age, lower income, or lower education, and in subjects without a spouse. ED prevalence was positively associated with risk factors such as diabetes, hypertension, heart disease, psychological stress, and obesity. Levels of serum hemoglobin (Hb) A1c, triglycerides, testosterone, or dehydroepiandrosterone sulfate (DHEA-S) were significantly different between the ED and non-ED groups. Conclusions The prevalences of ED and PE in Korean men were 13.4% (self-reported ED) and 11% (IELT ≤ 2-min), respectively. Risk factors and other socioeconomic and mental health factors were associated with ED prevalence. Biochemical factors such as HbA1c, triglycerides, testosterone, and DHEA-S were significantly related to ED prevalence.

Pericytes are known to play critical roles in vascular development and homeostasis. However, the distribution of cavernous pericytes and their roles in penile erection is unclear. Herein we report that the pericytes are abundantly distributed in microvessels of the subtunical area and dorsal nerve bundle of mice, followed by dorsal vein and cavernous sinusoids. We further confirmed the presence of pericytes in human corpus cavernosum tissue and successfully isolated pericytes from mouse penis. Cavernous pericyte contents from diabetic mice and tube formation of cultured pericytes in high glucose condition were greatly reduced compared with those in normal conditions. Suppression of pericyte function with anti-PDGFR-β blocking antibody deteriorated erectile function and tube formation in vivo and in vitro diabetic condition. In contrast, enhanced pericyte function with HGF protein restored cavernous pericyte content in diabetic mice, and significantly decreased cavernous permeability in diabetic mice and in pericytes-endothelial cell co-culture system, which induced significant recovery of erectile function. Overall, these findings showed the presence and distribution of pericytes in the penis of normal or pathologic condition and documented their role in the regulation of cavernous permeability and penile erection, which ultimately explore novel therapeutics of erectile dysfunction targeting pericyte function.

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Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED). Preclinical and clinical phase I studies showed that avanafil had enhanced selectivity, faster onset of action and a favourable side‐effect profile relative to currently available PDE5 inhibitors. As the result of phase III clinical trial for the efficacy and safety of avanafil treatment (100 and 200 mg), taken as needed over a period of 12 weeks, in Korean patients with ED, avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity. OBJECTIVE To evaluate the efficacy and safety of avanafil, a new potent selective phosphodiesterase type 5 (PDE5) inhibitor, in patients with erectile dysfunction (ED). PATIENTS AND METHODS The present study was a multicentre, randomized, double‐blind, placebo‐controlled, fix‐dosed phase three clinical trial involving 200 patients with ED. The subjects were treated with placebo or avanafil (100 or 200 mg) for 12 weeks and were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ). The primary outcome variable was the change from baseline for IIEF erectile function domain (EFD) score. The secondary outcome variables were SEP Q2 and Q3, the shift to normal rate (EFD ≥ 26), and response to the GAQ. RESULTS Compared with placebo, patients who took 100 or 200 mg of avanafil had significantly improved IIEF‐EFD score. There were similar results when comparing Q2 and Q3 in the SEP diary and the GAQ. Flushing was the most common treatment‐related adverse event. Most adverse events were transient and mild or moderate in severity. CONCLUSION Avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity.