Evaluation of tetrahydrobiopterin （BH4） as a potential therapeutic agent to treat erectile dysfunction

Aim： Nitric oxide （NO）-mediated smooth muscle relaxation causes penile erections. The endothelial NO synthase （eNOS） coenzyme tetrahydrobiopterin （BH4） converts eNOS-mediated catalytic activity from oxygen radical to NO production, improving endothelial function and vascular smooth muscle relaxation. Methods： Using quantitative immunohistochemistry, 8-isoprostane and nitrotyrosine concentrations were compared in cavernosal tissue from 17 potent and 7 impotent men, and the effect of single oral doses of BH4 on penile rigidity and tumescence was investigated. The pharmacodynamic effect of single oral doses of BH4 on penile rigidity and tumescence was investigated in a randomized, placebo-controlled, double-blind cross-over fashion in 18 patients with erectile dysfunction （ED） while receiving visual sexual stimulation. Results： 8-isoprostane content in endothelium and smooth muscle was signifi- cantly higher in impotent patient samples; the level of nitrotyrosine was unchanged in ED patients. Relative to placebo, a single dose of 200 mg BH4 led to a mean increase in duration of 〉 60% penile rigidity （33.5 rain [95% confidence interval （CI）： 13.1-49.3] at base and 29.4 rain [95% CI： 8.9-42,2] at tip）. A 500-mg dose increased the relative duration of 〉 60% penile rigidity by 36. I rain （95% CI： 16.3-51.8） at the base and 33.7 rain （95% CI： 11.4-43.9） at the tip. Treatments were well tolerated. Conclusion： BH4 treatment is suggested to switch eNOS catalytic activity from super-oxide to NO formation, leading to a reduced formation of free radical reaction product 8-isoprostane without alteration of nitrotyrosine. The observed results make BH4 a suitable candidate as an ED treatment through reconstitution of altered catalytic activity of the eNOS. （Asian JAndro12006 Mar; 8： 159-167）     

Effects of circumcision on male sexual functions： systematic review and meta-analysis

This meta-analysis was performed to assess sexual functions following adult male circumcision. We searched the Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, the Cochrane Database of Systematic Review and Web of Science from their inception until January 2013 to identify all eligible studies that reported on men＇s sexual function after circumcision. The Cochrane Collaboration＇s RevMan 5.2 software was employed for data analysis, and the fixed or the random effect model was selected depending on the proportion of heterogeneity. We identified 10 studies, which described a total of 9317 circumcised and 9423 uncircumcised men who were evaluated for the association of circumcision with male sexual function. There were no significant differences in sexual desire （odds ratio （OR）： 0.99; 95% confidence interval （CI）： 0.92-1.06）, dyspareunia （OR： 1.12; 95% Ch 0.52-2.44）, premature ejaculation （OR. 1.13; 95% Ch 0.83-1.54）, ejaculation latency time （OR： 1.33; 95% Ch 0.69-1.97）, erectile dysfunctions （OR： 0.90; 95% Ch 0.65-1.25） and orgasm difficulties （OR： 0.97; 95% Ch 0.83-1.13）. These findings suggest that circumcision is unlikely to adversely affect male sexual functions. However, these results should be evaluated in light of the low quality of the existing evidence and the significant heterogeneity across the various studies. Well-designed and prospective studies are required for a further understanding of this topic.     

他达拉非在埃及和土耳其男性勃起功能障碍患者中的疗效研究

在埃及和土耳其勃起功能障碍（ED）患者人群中，进行了一项随机化、双盲、平行分组、安慰剂对照研究，为期12周，对按需服用20mg他达拉非的疗效和安全性进行评估。共有132例患者入选该研究，接受随机化处理。研究结果表明，他达拉非在全部3项协同主要疗效终点上均优于安慰剂。“国际勃起功能指数”（IIEF）勃起功能（EF）域自基线起的平均变化值在他达拉非组中为9．3±0．8，而在安慰剂组中仅为2．3±1．6。     

他达拉非在西欧男性勃起功能障碍患者中的疗效和安全性

为了评估按需服用他达拉非在西欧轻度到重度男性ED患者人群中的安全性和疗效，研究者进行了一项随机化、双盲、安慰剂对照、多中心临床试验。患者根据ED的基线严重程度接受随机化处理，按照3：1的比例分别服用20mg他达拉非或安慰剂，共12周。主要疗效终点为“国际勃起功能指数”（IIEF）勃起功能（EF）域值以及对“性活动日志”（SEP）第2问（“你能将阴茎插入伴侣的阴道吗？”）和第3问（你的勃起持续时间足以成功完成性交吗？）的阳性回复百分率自基线到终点（12周）的平均变化值。