Efficacy and safety of phosphodiesterase type 5 inhibitors and selective serotonin reuptake inhibitors in the treatment of comorbiditiy of erectile dysfunction and premature ejaculation: a meta analysis / 现代泌尿外科杂志

【Objective】 To evaluate the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors alone or in combination with selective serotonin reuptake inhibitors (SSRIs) compared with SSRIs alone in the treatment of comorbidity of erectile dysfunction (ED) and premature ejaculation (PE). 【Methods】 The clinical randomized controlled trials of ED and PE comorbidity treated with PDE5 inhibitors alone or in combination with SSRIs were searched from database inception to Sep.2022, in CNKI, PubMed, Web of Science, Embase, Wanfang Database, cqVIP Database, SinoMed and Yiigle. The intravaginal ejaculatory latency time(IELT), score of International Index of Erectile Function 5 (IIEF-5) and adverse reaction rate were analyzed with RevMan 5.4.1 software. 【Results】 A total of9 studies involving 793 patients were included. Meta analysis showed that compared with SSRIs alone, PDE5 inhibitors alone or in combination with SSRIs yielded better results in IELT [MD=1.99, 95%CI(1.51-2.46), P<0.001] and higher IIEF-5 score [MD=4.61, 95%CI(3.68-5.55), P<0.001] , but no increase in adverse events [RR=0.99, 95%CI(0.74-1.31), P=0.92] . 【Conclusion】 In the treatment of ED and PE comorbidity, priority should be given to ED or both ED and PE, which can produce better efficacy without increasing the adverse effects.

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1,on unilateral renal interstitial fibrosis caused by ureteric obstruction in mice / 中国药理学通报

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.

Efficacy and safety of kidney -tonifying Chinese patent medicine combined with PDE 5 inhibitor in the treatment of erectile dysfunction ：a network meta -analysis / 中国药房

OBJECTIVE To systematically review the efficacy and safety of kidney -tonifying Chinese patent medicine combined with phosphodiesterase type 5（PDE5）inhibitors in the treatment of erectile dysfunction （ED），and to provide evidence - based reference for clinical medication . METHODS Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，VIP， China Biomedical Literature Database ，CNKI and Wanfang database ，randomized controlled trials （RCTs）of kidney -tonifying Chinese patent medicine combined with PDE 5 inhibitors（trial group ）versus PDE 5 inhibitors or kidney -tonifying Chinese patent medicine alone （control group ）were collected . The search period was from the establishment of the database to February 15，2022. After literature screening and data extraction ，the risk of bias assessment tool recommended in Cochrane System Reviewer ’s Handbook 6.1.0 was used to evaluate the quality of the included literature ；Stata 16.0 software was used for network meta -analysis； and the funnel plot was used for publication bias analysis . RESULTS A total of 23 RCTs were included ，with a total of 2 417 patients， involving 8 kinds of Chinese patent medicines ， including Congrong yishen granule ，Canrong zhutian capsule ， Compound xuanju capsule ， Huanshao capsule ， Shanhaidan granule， Shengjing capsule ， Shisanwei ziyin zhuangyang capsule，Shugan yiyang capsule . The results of network meta analysis showed that in terms of total effective rate ，Compound xuanju capsule combined with PDE 5 inhibitor，Shengjing capsule combined with PDE 5 inhibitor，Shugan yiyang capsule combined with PDE 5 inhibitor had higher total effective rate ；in terms of international index of erectile function 5，the scores of Compound xuanju capsule combined with PDE 5 inhibitor，Congrong yishen granule combined with PDE 5 inhibitor，and Canrong zhutian capsule combined with PDE 5 inhibitor were higher ；in terms of safety ，the incidence of adverse drug reactions caused by Huanshao capsule ，Shanhaidan granule and Shugan yiyang capsule were lower . CONCLUSIONS Kidney-tonifying Chinese patent medicine combined with PDE 5 inhibitor can improve the erectile function of ED patients and reduce the occurrence of adverse drug reactions . In terms of efficacy and safety ，Compound xuanju capsule combined with PDE 5 inhibitor is the best .

Positive outcomes of phosphodiesterase type 5 inhibitor on histopathologic and biochemical changes induced by ureteral obstruction

SUMMARY OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

RESUMO OBJETIVOS: Examinamos os efeitos do tadalafil em um dos inibidores da fosfodiesterase tipo 5 (PDE5) em um modelo de rato com obstrução ureteral unilateral parcial e completa (UUO). MÉTODOS: Os ratos foram divididos em cinco grupos: sham (n = 6), obstrução ureteral unilateral parcial (PUUO, n = 6), PUUO com tadalafil (PUUO T; Cialis, 10 mg/72 h, intragástrica; Lilly, Indianapolis, Indiana, EUA), completa obstrução ureteral unilateral (CUUO, n = 6) e CUUO com tratamento com tadalafil (CUUO T). RESULTADOS: Quinze dias após a UUO, o ureter apresentou alterações nas camadas de urotélio e infiltração significativa de células inflamatórias nos grupos PUUO e CUUO. Em comparação com os grupos sham, PUUO e CUUO, houve um aumento grave da infiltração de células inflamatórias. O epitélio urotelial exibiu degeneração e perda celular devido às células epiteliais inchadas, atróficas e desnudas nos grupos PUUO e CUUO. Nos grupos PUUO T e CUUO T, o urotélio revelou menor degeneração e perda de células epiteliais. Nós mostramos que a expressão da actina do músculo liso-α (α-SMA) e do fator de crescimento transformador-β (TGF-β) foram exibidas como sub-regulação nos grupos PUUO e CUUO. A expressão do TGF-β foi diminuída positivamente correlacionada com a da α-SMA nos grupos de terapia com tadalafil, PUUO T e CUUO T. CONCLUSÃO: O tadalafil do inibidor da fosfodiesterase tipo 5 reduziu as expressões α-SMA e TGF-β nos ureteres obstruídos, medidos por exames bioquímicos. Além disso, o tadalafil diminuiu a degeneração do urotélio devido à diminuição da perda de células epiteliais e da infiltração de células inflamatórias. Nossos resultados mostram que o tadalafil previne ou retarda o início da inflamação do ureter e degeneração urotelial em ratos com UUO.

Effect of phosphodiesterase type 5 inhibitors on prostate cancer / 国际外科学杂志

Erectile dysfunction was one of the most frequently postoperative complications after radical prostatectomy,which has been deeply concentrated by patients and urologists,along with more and more people were diagnosed as localized prostate cancer.Widely being used for erectile dysfunction after radical prostatectomy,the efficacy and safety of phosphodiesterase type 5 inhibitors have been confirmed by many clinical studies.However,the influences of phosphodiesterase type 5 inhibitors on the occurrence and progression of cancer are still not completely revealed at present.Additionally,the efficiency of phosphodiesterase type 5 inhibitors on biochemical recurrence after radical prostatectomny is still controversial,though it has been demonstrated that phosphodiesterase type 5 inhibitors is not associated with the occunrence of prostate cancer based on recent clinical studies.We will review the possibly mechanisms of phosphodiesterase type 5 inhibitors in oncologic occurrence,especially in the occurrence of prostate cancer and its biochemical recurrence after radical prostatectomy.

Advances in the concept of treatment of erectile dysfunction / 中华男科学杂志

Erectile dysfunction (ED) seriously influences the quality of life of the patients and their partners. There are various methods for the treatment of ED, with medication as the first choice. This paper reviews the advances in the concept of treatment of ED, including regular treatment, maximal therapeutic effects, primary diseases inducing ED, and humanistic environment and ideal goal of ED treatment, aiming to help further understand the therapeutic concept and improve clinical management of the disease.

A randomized clinical trial investigating treatment choice in Chinese men receiving sildenafil citrate and tadalafil for treating erectile dysfunction / 亚洲男科学杂志(英文版)

Sildenafil and tadalafil are efficacious and well tolerated in Chinese men with erectile dysfunction (ED). Recent study results indicate that men with ED in China who were naïve to phosphodiesterase inhibitor type 5 (PDE5) therapy prefer tadalafil 20-mg (on-demand) versus sildenafil 100-mg (on-demand). Differences in psychosocial outcomes may help to explain treatment preference in favor of tadalafil. This open-label, randomized, crossover study compared psychosocial outcomes and drug attribute choices between tadalafil and sildenafil in Chinese men with ED naïve to PDE5 inhibitor therapy. Eligible patients were randomized to sequential 20-mg tadalafil/100-mg sildenafil (n = 190) or 100-mg sildenafil/20-mg tadalafil (n = 193) for 8 weeks each and were asked which treatment they preferred to take for the 8-week extension phase. Psychosocial outcomes were assessed using the Psychological and Interpersonal Relationship Scale (PAIRS), Drug Attributes Questionnaire (DRAQ), and Sexual Life Quality Questionnaire (SLQQ). When taking tadalafil versus sildenafil, men had a higher mean endpoint score on the PAIRS Spontaneity Domain (tadalafil = 2.86 vs sildenafil = 2.72; P < 0.001), and a lower mean endpoint score on the Time Concerns Domain (tadalafil = 2.41 vs sildenafil = 2.55; P < 0.001). A numerical increase in the Sexual Self-Confidence Domain was observed when taking tadalafil versus sildenafil (tadalafil = 2.76 vs sildenafil = 2.72; P = 0.102). The most frequently chosen drug attributes explaining treatment preference were able to get an erection long after having drug, and ability to get an erection every time. SLQQ results were comparable between treatment groups. These psychosocial outcomes may explain why more Chinese men preferred tadalafil versus sildenafil for the treatment of ED in this clinical trial.

Role of Phosphodiesterase Type 5 Inhibitor on Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms / 대한남성과학회지

There is strong evidence from multiple epidemiological studies that benign prostate hyperplasia (BPH) induced lower urinary tract symptoms (LUTS) are correlated with erectile dysfunction (ED). Although a direct causal relationship is not established yet, four pathophysiological mechanisms can explain the relationship. These include alteration in activity of nitric oxide (NO)-cyclic GMP signal pathway, autonomic hyperactivity, increased Rho kinase/Rho A pathway and pelvic atherosclerosis. Androgens have been suggested to have an important role in the maintenance of the functional and structural integrity of the urinary tract. Sexual function should be assessed and discussed with the patient when choosing the appropriate management strategy for LUTS, as well as when evaluating the patient's response to treatment. Multiple large clinical trials have shown an improvement in LUTS after phosphodiesterase-5 (PDE5)-inhibitor treatment. Sildenafil is a pioneer of this clinical trial and appears to improve both erectile function and LUTS in subjects with ED. Basically PDE5 I with long half life is an appropriate candidate, therefore tadalafil and undenafil had been used to evaluate both diseases. Placebo-controlled trials of tadalafil showed improvement of LUTS secondary to BPH, but none of the studies showed a significant effect on urodynamic measures. PDE5 Is, such as sildenafil and tadalafil, increase the concentration of cGMP in plasma and smooth muscle, facilitating erection of the penis, relaxation of the bladder neck and prostate and subsequent bladder emptying. And theses PDE5 Is increase cAMP and cGMP levels and are more highly distributed in the prostate than plasma. These findings may help in the assessment of the feasibility of using PDE5 Is to concurrently treat both LUTS and ED.