We aimed to determine whether combination of LIM-kinase 2 inhibitor (LIMK2i) and phosphodiesterase type-5 inhibitor (PDE5i) could restore erectile function through suppressing cavernous fibrosis and improving cavernous apoptosis in a rat model of cavernous nerve crush injury (CNCI). Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows: (1) sham surgery (Group S), (2) CNCI (Group I), (3) CNCI treated with daily intraperitoneal administration of 10.0 mg kg^-1 LIMK2i (Group I + L), (4) daily oral administration of 20.0 mg kg^-1 udenafil, PDE5i (Group I + U), and (5) combined administration of 10.0 mg kg^-1 LIMK2i and 20.0 mg kg^-1 udenafil (Group I + L + U). Rats in Groups I + L, I + U, and I + L + U were treated with respective regimens for 2 weeks after CNCI. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissues were processed for histological studies and western blot. Group I showed lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining for alpha-smooth muscle (SM) actin, higher apoptotic index, lower SM/collagen ratio, increased phospho-LIMK2-positive fibroblasts, decreased protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) phosphorylation, increased LIMK2/cofilin phosphorylation, and increased protein expression of fibronectin, compared to Group S. In all three treatment groups, erectile responses, protein expression of fibronectin, and SM/collagen ratio were improved. Group I + L + U showed greater improvement in erectile response than Group I + L. SM content and apoptotic index in Groups I + U and I + L + U were improved compared to those in Group I. However, Group I + L did not show a significant improvement in SM content or apoptotic index. The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I + L and I + L + U, but not in Group I + U. Akt/eNOS phosphorylation was improved in Groups I + U and I + L + U, but not in Group I + L. LIMK2/cofilin phosphorylation was improved in Groups I + L and I + L + U, but not in Group I + U. Our data indicate that combined treatment of LIMK2i and PDE5i immediate after CN injury could improve erectile function by improving cavernous apoptosis or eNOS phosphorylation and suppressing cavernous fibrosis. Rectification of Akt/eNOS and LIMK2/cofilin pathways appears to be involved in their improvement.
Animals ; Apoptosis/drug effects* ; Arterial Pressure ; Electric Stimulation ; Erectile Dysfunction/pathology* ; Lim Kinases/antagonists & inhibitors* ; Male ; Nerve Crush ; Nitric Oxide Synthase Type III/metabolism* ; Penis/pathology* ; Peripheral Nerve Injuries/pathology* ; Phosphodiesterase 5 Inhibitors/therapeutic use* ; Phosphorylation ; Pyrimidines/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Sulfonamides/therapeutic use*

This study aimed to evaluate whether adding a vacuum erection device (VED) to regular use of Tadalafil could achieve better penile rehabilitation following posterior urethroplasty for pelvic fracture-related urethral injury (PFUI). Altogether, 78 PFUI patients with erectile dysfunction (ED) after primary posterior urethroplasty were enrolled and divided into two treatment groups: VED combined with Tadalafil (Group 1, n = 36) and Tadalafil only (Group 2, n = 42). Changes in penile length, testosterone level, International Index of Erectile Function-5 (IIEF-5) questionnaire, Quality of Erection Questionnaire (QEQ), and nocturnal penile tumescence (NPT) testing were used to assess erectile function before and after 6 months of ED treatment. Results showed that the addition of VED to regular use of Tadalafil preserved more penile length statistically (0.4 ± 0.9 vs -0.8 ± 0.7 cm, P < 0.01). IIEF-5 score and QEQ score in Group 1 were higher than Group 2 (both P < 0.05). After treatment, 21/36 (58.3%) Group 1 patients and 19/42 (45.2%) Group 2 patients could complete vaginal penetration. Group 1 patients also had markedly improved testosterone levels (P = 0.01). Unexpectedly, there was no significant difference in NPT testing between two therapies. For PFUI patients with ED after posterior urethroplasty, the addition of VED to regular use of Tadalafil could significantly improve their conditions - improving erection and increasing penile length - thus increasing patient satisfaction and confidence in penile rehabilitation.
Adult ; Combined Modality Therapy/methods* ; Erectile Dysfunction/rehabilitation* ; Humans ; Male ; Middle Aged ; Penile Erection ; Penis/surgery* ; Phosphodiesterase 5 Inhibitors/therapeutic use* ; Tadalafil/therapeutic use* ; Treatment Outcome ; Urethra/surgery* ; Vacuum ; Young Adult

BackgroundCurrently available evaluation criteria for penile tumescence and rigidity have been fraught with controversy. In this study, we sought to establish normative Chinese evaluation criteria for penile tumescence and rigidity by utilizing audiovisual sexual stimulation and RigiScan™ test (AVSS-Rigiscan test) with the administration of phosphodiesterase-5 inhibitor.

MethodsA total of 1169 patients (aged 18-67 years) complained of erectile dysfunction (ED) underwent AVSS-RigiScan test with the administration of phosphodiesterase-5 inhibitor. A total of 1078 patients whose final etiological diagnosis was accurate by means of history, endocrine, vascular, and neurological diagnosis, International Index of Erectile Function 5 questionnaire, and erection hardness score were included in the research. Logistic regression model and receiver operating characteristic curve analysis were performed to determine the cutoff value of the RigiScan™ data. Then, the multivariable logistic analysis was used in the selected variables.

ResultsA normal result is defined as one erection with basal rigidity over 60% sustained for at least 8.75 min, average event rigidity of tip at least 43.5% and base at least 50.5%, average maximum rigidity of tip at least 62.5% and base at least 67.5%, △tumescence (increase of tumescence or maximum-minimum tumescence) of tip at least 1.75 cm and base at least 1.95 cm, total tumescence time at least 29.75 min, and times of total tumescence at least once. Most importantly, basal rigidity over 60% sustained for at least 8.75 min, average event rigidity of tip at least 43.5%, and base at least 50.5% would be the new normative Chinese evaluation criteria for penile tumescence and rigidity. By multivariable logistic regression analysis, six significant RigiScan™ parameters including times of total tumescence, duration of erectile episodes over 60%, average event rigidity of tip, △tumescence of tip, average event rigidity of base, and △tumescence of base contribute to the risk model of ED. In logistic regression equation, predict value P < 0.303 was considered as psychogenic ED. The sensitivity and specificity of the AVSS-RigiScan test with the administration of phosphodiesterase-5 inhibitor in discriminating psychogenic from organic ED was 87.7% and 93.4%, respectively.

ConclusionsThis study suggests that AVSS-RigiScan test with oral phosphodiesterase-5 inhibitors can objectively assess penile tumescence and rigidity and seems to be a better modality in differentiating psychogenic from organic ED. However, due to the limited sample size, bias cannot be totally excluded.

Adolescent ; Adult ; Aged ; Erectile Dysfunction ; drug therapy ; metabolism ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Young Adult

Benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS) is a common disease with frequent occurrence in elderly men, and its incidence shows a significant positive correlation with age. Evidence has confirmed that BPH/LUTS is closely related to erectile dysfunction (ED) and significantly affects the quality of life of elderly males. Phosphodiesterase 5 inhibitors (PDE5i) can improve both ED and BPH/LUTS of the patients and PDE5 is expected to be a new therapeutic target for BPH/LUTS with ED. This review explores the structure and function of PDE5 and the action mechanisms of PDE5i so as to provide a more effective strategy for the clinical treatment of BPH/LUTS with ED.
Aged ; Drug Therapy, Combination ; Erectile Dysfunction ; complications ; drug therapy ; Humans ; Lower Urinary Tract Symptoms ; complications ; drug therapy ; Male ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Prostatic Hyperplasia ; complications ; drug therapy ; Quality of Life

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.
Adult ; Aged ; Asian People ; Double-Blind Method ; Erectile Dysfunction/drug therapy* ; Female ; Humans ; Male ; Middle Aged ; Patient Safety ; Phosphodiesterase 5 Inhibitors/therapeutic use* ; Product Surveillance, Postmarketing ; Prospective Studies ; Tadalafil/therapeutic use* ; Treatment Outcome ; Young Adult

The majority of men with spinal cord injury (SCI) suffer from different types and degrees of erectile dysfunction (ED). The impact of SCL on erectile function depends on the severity and location of the injury. Some patients can restore the residual sexual potential in the period of SCI recovery. Treatments of ED in men with SCI include psychotherapy, medication of oral PDE5 inhibitors, intracavernous injection of vasoactive drugs, transurethral medication, application of the vacuum erectile device and penile ring, penile prostheses, sacral neuromodulation, etc., among which PDE5 inhibitors remain the first option and usually give good clinical results for those with higher SCI. However, intracavernous injection of vasoactive drugs and combined treatment are preferable for those with lower SCI.
Erectile Dysfunction ; etiology ; therapy ; Humans ; Male ; Penile Prosthesis ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Psychotherapy ; Spinal Cord Injuries ; complications

Objective: To evaluate the safety, efficacy and tolerability of China-made sildenafil citrate (Jinge) in the treatment of ED. METHODS: We conducted a multi-center, randomized, double-blind and placebo-controlled clinical trial among 222 ED patients in five urological or andrological clinics of China. The patients were randomly assigned to receive sildenafil citrate (SC, n = 111) or placebo (n = 111) for 8 weeks. We obtained and analyzed the demographic and clinical characteristics of the patients, the scores of International Index of Erectile Function (IIEF), the success rate of sexual intercourse, and the incidence of adverse events. RESULTS: No statistically significant differences were found between the patients of the SC and those of the placebo group in the mean age (［47.2±11.32］ yr vs ［46.67±13.08］ yr, P>0.05), psychological etiology (27.93% vs 23.42%, P>0.05), organic etiology (21.62% vs 29.73%, P>0.05) or mixed etiology (50.45% vs 46.85%, P>0.05), nor in height, weight, nationality, or history of smoking, drinking or allergy. Compared with the placebo controls, the SC-treated patients showed significant increases in the excellence rate of effectiveness (29.91% vs 78.90%, P<0.01), success rate of sexual intercourse (29.16% vs 63.87%, P<0.01), and total effectiveness rate (34.58% vs 77.98%, P<0.01). The effectiveness rates on organic, psychogenic and mixed types ED were remarkably higher in the SC group (64.52%, 83.33%, and 82.14%) than in the placebo control (46.15%, 21.21%, and 25.00%) (P<0.01). Mild or temporary adverse events were observed in 32 cases in the SC group as compared with 13 in the placebo control. CONCLUSIONS China-made sildenafil citrate is an effective, safe and well-tolerated drug for ED of different etiologies in the Chinese population.
Aged ; China ; Coitus ; Double-Blind Method ; Drug Compounding ; Erectile Dysfunction ; drug therapy ; etiology ; Humans ; Male ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Sildenafil Citrate ; therapeutic use ; Smoking ; Treatment Outcome

Objective: To investigate the safety and efficacy of pancreatic kininogenase combined with sildenafil in the treatment of erectile dysfunction(ED) in type 2 diabetes mellitus (DM) patients in the high-altitude area. METHODS: This study included 93 ED patients with type 2 DM, all residents of the Xining area 1500 meters above sea level. We randomly divided them into an experimental group (n = 48) and a control group (n = 45), the former treated with pancreatic kininogenase(120 u, tid) and sildenafil (25 mg, qd at bedtime), while the latter with sildenafil only (25 mg, qd at bedtime).After 4 and 8 weeks of medication, we obtained the penile hemodynamic parameters,IIEF-5 scores, and sexual intercourse satisfaction(SIS) scores and compared them between the two groups of patients. RESULTS: There were no statistically significant differences in age or DM course between the two groups of patients (P >0.05).Compared with the baseline, both the experimental and control groups showed remarkably improvement inthe IIEF-5 score (8.81 ± 2.06 vs 11.54 ± 7.72 and 8.29 ± 1.91 vs 9.37± 1.65, P <0.05), SIS score (3.35 ± 2.43vs6.83± 2.61and 3.41 ± 2.38 vs 4.92± 2.49, P <0.05), and penile hemodynamic parameters obtained by color duplex Doppler ultrasonography(P <0.05), with significant differences between the two groups in the IIEF-5 score (11.54 ± 7.72 vs 9.37± 1.65, P <0.05) and SIS score (6.83± 2.61 vs 4.92± 2.49, P <0.05) but not in the penile hemodynamic parameters (P >0.05). Even more remarkable improvement was observed at 8 weeks in the experimental and control groups in the IIEF-5 score (19.29± 1.85 and 15.43± 1.74)(P <0.05), SIS score (11.73 ± 2.57 and 6.55± 2.71) (P <0.05), and penile hemodynamic parameters(P <0.05), all with significant differences between the two groups (P <0.05). CONCLUSIONS Pancreatic kininogenase combined with sildenafil has a better clinical effect than sildenafil alone on ED in type 2 DM patientsin the high-altitude area.
Aged ; Altitude ; Coitus ; Diabetes Mellitus, Type 2 ; complications ; Drug Therapy, Combination ; Erectile Dysfunction ; etiology ; therapy ; Humans ; Kallikreins ; therapeutic use ; Male ; Pancreas ; enzymology ; Penile Erection ; drug effects ; physiology ; Penis ; physiology ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Sildenafil Citrate ; therapeutic use ; Treatment Outcome

Prostate cancer has the highest incidence among malignant tumors of the urinary system in China. Radical prostatectomy (RP) is the most effective treatment for localized prostate cancer with a good long-term prognosis. Erectile dysfunction (ED) is a common complication after RP, which seriously affects the patient's quality of life. With the rising incidence and early diagnosis of prostate cancer, the proportion of young cases of RP is increasing, and so is the importance of the treatment of post-RP ED. The restoration of erectile function after RP is closely related to the timing of penile rehabilitation as well as to pre- and intra-operative measures such as surgical strategies and methods. Common options for the treatment of post-RP ED include oral medication of phosphodiesterase type 5 inhibitors, application of vasoactive substances in the urethra or corpus cavernosum, use of vacuum erection devices, and implantation of penile prosthesis. Stem cell therapy, nerve transplantation, low-intensity extracorporeal shockwave therapy, and erythropoietin have shown great potential in penile rehabilitation after RP. At present, the stress is placed on the remission of symptoms in the treatment of ED. Stem cell therapy may reverse the cause of disease or cure ED by reversing its pathophysiological changes. A series of clinical trials of stem cell therapy are underway and have preliminarily confirmed the safety of stem cell therapy and proved that it can improve erectile function in patients with post-RP ED. This review focuses on the progress in the prevention and treatment of ED after RP.
China ; Erectile Dysfunction ; prevention & control ; therapy ; Humans ; Male ; Penile Erection ; Penile Prosthesis ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Postoperative Complications ; prevention & control ; therapy ; Prostatectomy ; adverse effects ; Prostatic Neoplasms ; surgery ; Quality of Life ; Stem Cell Transplantation ; Treatment Outcome ; Vacuum ; Vasodilator Agents ; therapeutic use

Premature ejaculation (PE) is a common male sexual disorder with an incidence rate of 20-30%. Recent clinical trials have demonstrated that phosphodiesterase type 5 inhibitors (PDE5i), as the first-line drug for erectile dysfunction (ED), can improve ejaculatory function probably by acting on the peripheral and central adrenergic nerves. The possible action mechanisms of PDE5i may involve lessening of the central sympathetic output, modulation of the contractile responses from the vas deferens, seminal vesicles, prostate and urethra, induction of peripheral analgesia, and prolonging of the total erectile duration, increasing the confidence of ejaculation control, and reducing the post-ejaculation refractory time. This review discusses the possible mechanisms and clinical application of PDE5i in the treatment of PE.
Ejaculation ; drug effects ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Muscle Contraction ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Premature Ejaculation ; drug therapy ; Seminal Vesicles ; physiology ; Vas Deferens ; physiology