sildenafil-citrate and Penile-Induration

The FDA approval of Viagra (sildenafil) for the on demand treatment of erectile dysfunction (ED) through relaxation of the corporal and cavernosal vascular smooth muscle that results in an increase in blood flow to the corporal tissues stemmed from 2 decades of research, mainly at academic centers. This culminated in the finding of the nitric oxide/cGMP pathway as the mediator of penile erection, followed by some years of basic studies and clinical validation at Pfizer. Further on, new translational laboratory and animal research from our group initiated a second phase when we proposed an alternative therapeutic schedule and mechanism of action for PDE5 inhibitors (PDE5i) in both corporal veno-occlusive dysfunction (CVOD) and Peyronie's disease (PD), specifically, continuous long-term administration (CLTA) to achieve sustained levels of cGMP within the penis. Due to the extended half-life of the long-acting PDE5i, tadalafil, this new alternative encompasses preferentially daily administration, although shorter half-life PDE5i, like sildenafil and vardenafil work too, depending on the duration, dose, and frequency of their administration This novel use was initially supported by showing the antifibrotic/antioxidant effects of nitric oxide and cGMP, produced by the induction of iNOS, as a mechanism of defense against collagen deposition in the localized fibrotic plaque of PD in an avascular tissue, the tunica albuginea. Our studies on iNOS and the progressive diffuse fibrosis occurring in the smooth muscle in CVOD, led to proposing the CLTA of PDE5i for maintaining sustained cGMP levels both in PD and in CVOD in order to halt or regress the penile fibrosis. In CVOD, we showed that PDE5i protect the corporal smooth muscle and reduce myofibroblast activation and number, counteracting the underlying corporal tissue pathology that causes CVOD, and potentially ameliorating long-term CVOD or even curing it. This review is focused on this novel PDE5i anti-fibrotic therapeutic concept.

Topics: Animals; Arterial Occlusive Diseases; Cyclic GMP; Disease Models, Animal; Drug Evaluation, Preclinical; Erectile Dysfunction; Humans; Male; Muscle, Smooth; Nitric Oxide Synthase Type II; Penile Induration; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Translational Research, Biomedical

Stem cells (SCs) have been investigated for the treatment of erectile dysfunction (ED).. This review covers key disease targets and all 33 preclinical studies, including their use of SC types, animal models, transplantation routes, and outcome assessment methods.. In the past one and half years there have been more stem-cell-for-erectile-dysfunction studies than the prior 8 years combined. These new studies tend to use combinatory treatment approaches by modifying or supplementing SCs with angiogenic or neurotrophic genes or proteins. However, when considering all risks and benefits, these combinatory approaches do not seem more advantageous than single-SC approaches. Another trend is the choice of transplantation routes other than the standard intracavernous (IC) injection. However, with the exception of intravenous injection, these new transplantation approaches are more cumbersome than IC injection and yet offer no evidence of producing better outcomes. In contrast to these variations, a consensus among these studies is the suggestion that paracrine action, as opposed to cellular differentiation, is the principal therapeutic mechanism. In conclusion, IC injection of a single SC type should be the choice protocol for initial clinical trials, and this is clearly the case with two clinical trials that are currently recruiting patients.

Topics: Animals; Clinical Trials as Topic; Diabetes Complications; Disease Models, Animal; Erectile Dysfunction; Evaluation Studies as Topic; Humans; Injections, Intravenous; Male; Myocytes, Smooth Muscle; Organ Specificity; Paracrine Communication; Penile Induration; Piperazines; Postoperative Complications; Prevalence; Prostatectomy; Purines; Radiotherapy; Rats; Sildenafil Citrate; Stem Cell Transplantation; Sulfones; Treatment Outcome

Despite the revolutionary introduction of oral erectogenic agents for the treatment of erectile dysfunction, there will always be patients who do not respond to conservative therapy. Penile prosthetic surgery remains an important option for these patients. Mechanical reliability and patient satisfaction have improved significantly throughout the years. This review focuses on the most recent and important updates regarding product enhancements, patient satisfaction studies, and management of intra- and postoperative problems.

Topics: Erectile Dysfunction; Forecasting; Humans; Intraoperative Complications; Male; Patient Satisfaction; Patient Selection; Penile Induration; Penile Prosthesis; Phosphodiesterase Inhibitors; Piperazines; Postoperative Complications; Preoperative Care; Purines; Reproducibility of Results; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome

Since Food and Drug Administration approval of collagenase. A randomized, controlled trial was performed of Peyronie's disease men treated with either collagenase. A total of 40 men were enrolled, with 38 (collagenase. At 3 months posttreatment, collagenase

Topics: Clostridium histolyticum; Collagenases; Erectile Dysfunction; Humans; Injections, Intralesional; Male; Microbial Collagenase; Penile Induration; Penis; Sildenafil Citrate; Treatment Outcome

The aim of this study was to investigate the impact of the addition of 50 mg daily sildenafil to pentoxifylline-colchicine combination ther-apy on the Peyronie's plaque features in patients with the acute phase of Peyronie's disease (PD).. In this retrospective and non-randomized clinical study, patients were divided into 2 groups as group 1; (n = 107) who received colchicine and pentoxyfillin plus 50 mg daily oral sildenafil, and as group 2; (n = 79) who received only colchicine and pentoxyfillin. Patients were compared in terms of degree of curvature, pain in erection and erectile function at the baseline and at 6-month follow up. Pain in erection and erectile func-tion were evaluated by visual Analogue Scale (EF-VAS), and the shortened version of the International Index of Erectile Function (IIEF-5). Improvement in the degree of curvature and change in EF-VAS scores were primary endpoints of the study. Change in IIEF-5 score was the secondary endpoint of the study.. The two groups were statistically similar in terms of demographics and baseline features of PD. A statistically signifi-cant reduction in degree of curvature and EF-VAS scores was shown in group 1 compared to group 2.There was also a signifi-cantly higher IIEF-5 score in group 1 compared to group 2. No significant side effects were detected in both groups during treatment period.. Adding sildenafil to pentoxifylline-colchicine com-bination treatment seems to improve PD related symptoms in the acute phase PD. PDE5i may contribute to relieve the Peyronie's symptoms in ED patients through their antifibrotic effects.

Topics: Colchicine; Erectile Dysfunction; Humans; Male; Pain; Penile Induration; Penis; Pentoxifylline; Retrospective Studies; Sildenafil Citrate; Treatment Outcome

The effectiveness of phosphodiesterase type 5 (PDE5) inhibitors over the conservative management of Peyronie's disease (PD) has been widely questioned.. To determine the role of sildenafil 25 mg film formulation twice a day (S25 b.i.d.) in the improvement of curvature after treatment of collagenase of Clostridium hystoliticum (CCH) in penile curvature owing to PD.. From April 2017 to April 2018, 161 consecutive patients were treated with S25 b.i.d. + CCH or CCH alone. Adjustment variables consisted of age, penile curvature, and the 15-question International Index of Erectile Function (IIEF-15) questionnaire at baseline using 1:1 propensity-score matching. Overall, 50 patients were considered subdivided into the following: 25 patients who received S25 b.i.d. + CCH (group A) and 25 who received CCH alone (group B). Patients received CCH injection using a shortened protocol and vacuum device in both groups.. The primary outcome of the study was the change in penile curvature after treatment, and secondary outcomes were the change in sexual function (IIEF-15) and in the Peyronie's Disease Questionnaire (PDQ) and its subscores, PDQ-PS (psychosexual symptoms), PDQ-PP (penile pain), and PDQ-SB (symptom bother).. Overall, mean penile curvature was 47.0° (SD 21.88), the mean IIEF-EF (erectile function) was 23.56 (SD 4.10), and the mean PDQ was 27.06 (SD 13.55). After the treatment, we observed a mean change for penile curvature of 25.6 (SD 9.05) in group A and -25.6 (SD 9.7) in group B (P < .01), for IIEF-EF of 2.28 (SD 2.33) in group A and 1.36 (SD 1.77) in group B (P = .03), for PDQ-PS of -3.04 (SD 2.95) in group A and of -2.12 (SD 2.06) in group B (P = .11), for PDQ-PP of -1.0 (SD 4.48) in group A and of -0.88 (SD 2.04) in group B (P = .60), for PDQ-SB of -5.84 (SD 4.58) in group A and of -4.16 (SD 4.45) in group B (P = .60), and for Female Sexual Function Index of 3.8 (SD 2.45) in group A and of 2.72 (SD 2.28) in group B (P = .14). We found a rate of global satisfaction of 70.83% in group A and of 84.0% in group B (P = .27).. Addition of S25 b.i.d. to CCH is superior to CCH alone for improving penile curvature and erectile function.. This is the first study comparing sildenafil + CCH vs CCH alone for the treatment of PD. Lack of randomization and direct verification of appropriate use of penile modeling could be considered limitations.. In this study, combination therapy was superior in terms of penile curvature and erectile dysfunction improvement. Cocci A, Cito G, Urzì D, et al. Sildenafil 25 mg ODT + collagenase Clostridium hystoliticum vs collagenase Clostridium hystoliticum alone for the management of Peyronie's disease: A matched-pair comparison analysis. J Sex Med 2018;15:1472-1477.

Topics: Adult; Aged; Drug Therapy, Combination; Humans; Injections, Intralesional; Male; Microbial Collagenase; Middle Aged; Penile Induration; Penis; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents

It has been shown on experimental rat models that type 5-phosphodiesterase isoenzyme (PDE5) inhibitors have anti-fibrotic effects for Peyronie's disease (PD); however, this issue has not been addressed clinically. The aim of this study was to document the effects of PDE5 inhibitors used for erectile dysfunction (ED) seen in PD patients on the main course of the PD clinically.. A total of 39 PD patients with ED were divided into two groups. Patients in Group 1 (n = 18) served as controls and received 400 IU vitamin E per day. Those in Group 2 (n = 21) received 50 mg sildenafil per day for 12 weeks. Penile plaque volume was assessed by palpation and by duplex ultrasound. Erectile capacity, penile deformity and plaque characteristics were assessed by the International Index of Erectile Function questionnaire form (IIEF-5) and penile duplex ultrasound.. Statistically significant improvement in all parameters was observed within both groups except for IIEF score in Group 1 when compared with the initial values. Significant reduction in plaques and pain were observed in 7 (33.3 %) and 14 (66.6 %) patients in Group 2 and 6 (33.3 %) and 9 patients (42.8 %) in Group 1, respectively. At the end of the therapy, improvement in IIEF score and reduction in pain were statistically significant in Group 2 compared with Group 1 (p = 0.028 and p = 0.045, respectively).. We conclude that continuous administration of oral PDE5 inhibitors may be a candidate for medical treatment of PD; however, more controlled studies are needed.

Topics: Administration, Oral; Adult; Animals; Comorbidity; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Induration; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Rats; Sildenafil Citrate; Sulfones; Treatment Outcome; Ultrasonography, Doppler, Duplex

Topics: Humans; Male; Penile Induration; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Tamoxifen; Triazines; Vardenafil Dihydrochloride

Testosterone (T) deficiency is associated with erectile dysfunction (ED). The relaxant response of T on the corporal smooth muscle through a non-genomic pathway has been reported; however, the in vitro modulating effects of T on human corpus cavernosum (HCC) have not been studied.. To compare the effects of various concentrations of T on nitric oxide (NO)-dependent and nitric oxide-independent relaxation in organ bath studies and elucidate its mode of action, specifically targeting the cavernous NO/cyclic guanosine monophosphate (cGMP) pathway.. Human corpus cavernosum (HCC) samples were obtained from men undergoing penile prosthesis implantation (n = 9). After phenylephrine (Phe) precontraction, the effects of various relaxant drugs of HCC strips were performed using organ bath at low (150 ng/dL), eugonadal (400 ng/dL), and hypergonadal (600 ng/dL) T concentrations. The penile tissue measurements of endothelial nitric oxide synthase (eNOS), neuronal (n)NOS, and phosphodiesterase type 5 (PDE5) were evaluated via immunostaining, Western blot, cGMP and nitrite/nitrate (NOx) assays.. Relaxation responses to ACh and EFS in isolated HCC strips were significantly increased at all T levels compared with untreated tissues. The sildenafil-induced relaxant response was significantly increased at both eugonadal and hypergonadal T levels. Normal and high levels of T are accompanied by increased eNOS, nNOS, cGMP, and NOx levels, along with reduced PDE5 protein expression.. This study reveals an important role of short-term and modulatory effects of different concentrations of T in HCC. T positively regulates functional activities, inhibition of PDE5 expression, and formation of cGMP and NOx in HCC. These results demonstrate that T indirectly contributes to HCC relaxation via downstream effects on nNOS, eNOS, and cGMP and by inhibiting PDE5. This action provides a rationale for normalizing T levels in hypogonadal men with ED, especially when PDE5 inhibitors are ineffective. T replacement therapy may improve erectile function by modulating endothelial function in hypogonadal men.

Topics: Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Hormone Replacement Therapy; Humans; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Penile Induration; Penis; Sildenafil Citrate; Testosterone

Topics: Clostridium; Collagenases; Humans; Male; Microbial Collagenase; Penile Induration; Sildenafil Citrate

Topics: Adult; Age Factors; Anti-Inflammatory Agents; Biopsy; Erectile Dysfunction; Follow-Up Studies; Humans; Hydrocortisone; Kidney; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Penile Induration; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vasodilator Agents; Verapamil

Peyronie's disease (PD) is correctable by several surgical approaches including plaque incision with grafting. While the best choice of graft material remains controversial, the risk of postoperative erectile dysfunction (ED) is apparent across previous reports.. We attempt to provide guidelines as to which patients may be at increased risk for developing postoperative ED after this procedure, as well as examine the role of sildenafil citrate (SC) in the postoperative period for prevention of this complication.. A retrospective review was performed on 37 patients who underwent surgical correction of PD with pericardial grafting after plaque incision. Mean follow-up was 24 months. We evaluated patient age, duration of disease, defect size, plaque location, degree of curvature, shaft narrowing, preoperative coital activity, vascular risk factors for ED, as well as preoperative erection grade and duplex ultrasound parameters. Twenty-six of these patients underwent a postoperative rehabilitation protocol of SC to enhance recovery of unassisted erections.. Overall, 11 patients (29%) noted diminished postoperative rigidity, that compromised unassisted coitus, compared to preoperative status. Comparison of rates of ED among those with or without vascular risk factors yielded no statistically significant results. Peyronie's disease duration, patient age, defect size, plaque location, degree of curvature, and narrowing were also insignificant predictors of which patients developed ED. An increased percentage of patients who developed ED were not sexually active preoperatively compared to those that did not develop ED (58% vs. 80%). When patients were compared based on preoperative erection grade, those patients with compromised erectile function were more likely to develop postoperative ED vs. those with full erections (P < 0.05). No significant differences were found in preoperative duplex ultrasound parameters between both sets of patients. For those undergoing SC rehabilitation, 7 out of 26 (26%) developed ED in comparison to 4 out of 11 patients (36%) developing diminished rigidity when not subjected to the protocol.. No single parameter was found that predicted the occurrence of postoperative ED with the exception of preoperative erectile status. The surgeon must carefully assess and consult each patient when considering grafting as well as consider the possible role of SC in attempting to prevent this complication.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Induration; Pericardium; Phosphodiesterase Inhibitors; Pilot Projects; Piperazines; Postoperative Complications; Purines; Retrospective Studies; Risk Factors; Sexual Behavior; Sildenafil Citrate; Sulfones

Inducible nitric oxide synthase (iNOS) is expressed in both the fibrotic plaque of Peyronie's disease (PD) in the human, and in the PD-like plaque elicited by injection of TGFbeta1 into the penile tunica albuginea (TA) of the rat. Long-term inhibition of iNOS activity, presumably by blocking nitric oxide (NO)- and cGMP-mediated effects triggered by iNOS expression, exacerbates tissue fibrosis through an increase in: (a) collagen synthesis, (b) levels of reactive oxygen species (ROS), and (c) the differentiation of fibroblasts into myofibroblasts. We have now investigated whether: (a) phosphodiesterase (PDE) isoforms, that regulate the interplay of cGMP and cAMP pathways, are expressed in both the human and rat TA; and (b) L-arginine, that stimulates NOS activity and hence NO synthesis, and PDE inhibitors, that increase the levels of cGMP and/or cAMP, can inhibit collagen synthesis and induce fibroblast/myofibroblast apoptosis, thus acting as antifibrotic agents. We have found by immunohistochemistry, RT/PCR, and Western blot that PDE5A-3 and PDE4A, B, and D variants are indeed expressed in human and rat normal TA and PD plaque tissue, as well as in their respective fibroblast cultures. As expected, in the PD fibroblast cultures, pentoxifylline (non-specific cAMP-PDE inhibitor) increased cAMP levels without affecting cGMP levels, whereas sildenafil (PDE5A inhibitor) raised cGMP levels. Both agents and L-arginine reduced the expression of collagen I (but not collagen III) and the myofibroblast marker, alpha-smooth muscle actin, as determined by immunocytochemistry and quantitative image analysis. These effects were mimicked by incubation with 8-Br-cGMP, which in addition increased apoptosis, as measured by TUNEL. When L-arginine (2.25 g/kg/day), pentoxifylline (10 mg/kg/day), or sildenafil (10 mg/kg/day) was given individually in the drinking water for 45 days to rats with a PD-like plaque induced by TGF beta1, each treatment resulted in a 80-95% reduction in both plaque size and in the collagen/fibroblast ratio, as determined by Masson trichrome staining. Both sildenafil and pentoxiphylline stimulated fibroblast apoptosis within the TA. Our results support the hypothesis that the increase in NO and/or cGMP/cAMP levels by long-term administration of nitrergic agents or inhibitors of PDE, may be effective in reversing the fibrosis of PD, and more speculatively, other fibrotic conditions.

Topics: Animals; Apoptosis; Arginine; Blotting, Western; Cyclic GMP; Enzyme Inhibitors; Fibrosis; Humans; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Penile Induration; Penis; Pentoxifylline; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Rats; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sildenafil Citrate; Sulfones

Erectile dysfunction (ED) has frequently been associated with Peyronie's Disease (PD) and may further compromise coitus. This is a retrospective analysis of ED in patients with PD since the release of sildenafil citrate (SC) focusing specifically on our patients' responses to SC. One-hundred seventy six patients with PD were evaluated between April 1998 and May 2001. All patients received a complete medical and sexual history, physical exam, penile duplex ultrasound (PDU, with 30-90 mg of papaverine) to assess penile vascular integrity, plaque dimensions, and erect penile deformity. Based on these findings, appropriate treatment options were offered for their PD and their ED including SC, which was offered to 73 men. Patient response to SC was specifically assessed during patient office interview and via a mailed EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) questionnaire. Seventy (39.8%) and 104 (59.1%) patients complained of decreased erectile capacity (ie rigidity) occurring before and after the onset of PD, respectively. Only two patients reported no change of erectile capacity. In all, 103 (58.5%) patients complained of significant reduction in sexual function due to diminished rigidity and sought treatment for their ED. Of the ED treatment options available, 73 (70.9%) patients were given a prescription for SC. Forty-eight (75.0%) patients returned the EDITS questionnaire while four of 73 (5.5%) patients did not fill their prescription and five of 73 (6.8%) did not engage in sexual activity following an initial trial of SC due to side effects (flushing, headaches). Based upon the EDITS response, 34 of 48 (70.8%) patients reported that they were either very satisfied or somewhat satisfied, five of 48 (10.4%) patients were neither satisfied nor dissatisfied, and nine of 48 (18.8%) patients were somewhat dissatisfied or very dissatisfied with the effectiveness of SC in enhancing their erectile response. No patient reported worsening of PD deformity or an increase in penile pain. The 30 patients who were not prescribed SC chose the following options to enhance rigidity: eight (7.8%) underwent prosthesis placement, four (3.9%) opted for vacuum constriction device (VCD), four (3.9%) chose intracorporal injections, and 14 (13.6%) used no adjunctive therapy. Erectile dysfunction is a problem associated with PD and all typical treatment options are acceptable. However, to our knowledge, there is no published study reviewing the efficacy of

Topics: Arteries; Erectile Dysfunction; Humans; Male; Patient Satisfaction; Penile Induration; Penis; Phosphodiesterase Inhibitors; Piperazines; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Vascular Diseases

We determined the effect of incision and saphenous vein grafting on penile length, erectile function and overall sexual satisfaction in men with Peyronie's disease.. A total of 24 consecutive men underwent plaque incision and saphenous vein grafting with postoperative daily use of a vacuum erection device. Erect penile length, pain, curvature and erectile function were assessed before and after surgery, and overall sexual satisfaction was scored from 1 to 5 by a validated instrument.. Of the 22 patients in whom adequate followup data were available mean penile length was increased 2.1 cm. as a result of surgery (p <0.001). Median score of overall satisfaction with sex life was 4 or moderately satisfied. Of the 86% of men who achieved sexual intercourse after surgery 54% used no erectile aids and 32% required sildenafil or intracavernous injection. Complete erectile dysfunction was present in 14% of cases. Patients who reported erectile difficulty preoperatively were significantly more likely to have erectile dysfunction postoperatively that required erectile aids. Arterial insufficiency on duplex Doppler ultrasound was associated with a higher likelihood of complete erectile dysfunction. Complications in 33% of patients included complete erectile dysfunction in 3 and significant persistent penile curvature in 1.. Incision and venous grafting of plaque leads to statistically and clinically significant increases in penile length in men with Peyronie's disease. Preoperative erectile dysfunction and cavernous arterial insufficiency were associated with a higher risk of postoperative erectile dysfunction. Nevertheless, patients reported a high degree of satisfaction with their overall sex life.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Erection; Penile Induration; Penis; Phosphodiesterase Inhibitors; Piperazines; Postoperative Complications; Purines; Saphenous Vein; Sexual Behavior; Sildenafil Citrate; Sulfones