sildenafil-citrate and Prostatism

To critically review the physiological roles of phosphodiesterase-5 (PDE5), to explain and support the putative impact and clinical significance of PDE5 inhibitors (PDE5-Is) in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both highly prevalent in men aged > or =50 years, as PDE5-Is are very effective as a first-line therapy for ED, and attractive for further physiological functional investigations.. We searched Medline for peer-reviewed articles in English, from 1991 to 2008, to provide a critical contemporary review of PDE5 pertaining to the potential interest of findings supporting a role for PDE5-Is in LUTS due to BPH. The selection of papers was based on the relevance of subject matter. A critical analysis of available fundamental and clinical data is reported.. Several studies assessed the role of the nitric oxide/cGMP signalling pathway in the regulation of the prostate tone, with the support of clinical observations. PDE5-Is can also represent a potential mode of action allowing the targeting of transcriptional activity implicated in the regulation of the progression of the inflammatory process involved in BPH. PDE5-Is can inhibit human stromal cell proliferation of the prostate mediated by cGMP accumulation. New targeting hypotheses of pathophysiological processes are also reported.. There is evidence that LUTS and ED are strongly linked. This analysis of the regulatory basis of PDE5 biology could indicate several directions of investigation. However, it is necessary to devise well-designed large prospective studies that would produce significant data before this approach becomes a standard of care.

Topics: Aged; Carbolines; Erectile Dysfunction; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Prostatism; Purines; Quality of Life; Quinazolines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To evaluate the efficacy of sildenafil citrate only, 25 mg. Four times/week, tamsulosin only, 0.4 mg once daily, and the combination of both on lower urinary tract symptoms (LUTS) suggestive of benign prostate hyperplasia (BPH) and erectile dysfunction.. A total of 60 men with BPH-related LUTS were randomized to receive sildenafil citrate only (n = 20), tamsulosin only (n = 20), and the combination of both (n = 20) for 8 weeks. Changes from baseline in International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q (max)), post voiding residual urine volume (PRV), Sexual Health Inventory for Male (SHIM) score, 3rd and 4th questions of International Index of Erectile Function (IIEF) were assessed at the end of the treatment.. The mean age was 58 years. IPSS, Q (max), PRV, SHIM scores, and 3rd and 4th questions in IIEF significantly improved in each group. Improvement of IPSS was more remarkable in combination (40.1%) and tamsulosin only (36.2%) groups in comparison with sildenafil citrate only group (28.2%; p < 0.001). Improvement of Q (max) and PRV were greater in tamsulosin only and combination than sildenafil citrate only group. SHIM scores significantly improved in sildenafil citrate only (65%) and combination (67.4%) than tamsulosin only (12.4%; p < 0.001). Increases in the 3rd and 4th questions of IIEF were greater in sildenafil only and combination than tamsulosin only (p < 0.001).. Treatment with the combination of tamsulosin only and sildenafil citrate only was not superior to tamsulosin only to enhance voiding symptoms. Also, sexual function improvement was similar for both the combination and sildenafil citrate only treatments.

Topics: Adrenergic alpha-Antagonists; Aged; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Prostatism; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Tamsulosin

To evaluate once-daily 100-mg sildenafil for the treatment of erectile dysfunction (ED) in men with ED and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).. This was a 12-week, randomised, double-blind, placebo-controlled (DBPC) trial, with an 8-week open-label (OL) extension, in men > or = 45 years of age who scored < or = 25 on the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and > or = 12 on the International Prostate Symptom Score.. At DBPC end of treatment (EOT), the sildenafil group (n = 189, vs. placebo, n = 180) had improved EF (IIEF), improved emotional well-being [Self-Esteem And Relationship questionnaire (SEAR)], and greater treatment satisfaction (Erectile Dysfunction Inventory of Treatment Satisfaction) (p < 0.0001). At OL EOT, IIEF and SEAR scores improved slightly in the group previously randomised to sildenafil (n = 168), but much more in the group previously randomised to placebo (N = 155), such that total improvement over the 20-week trial was comparable between the groups. Erections at baseline were hard enough for penetration on approximately half of occasions and lasted long enough for successful intercourse on less than one quarter of occasions, increasing at sildenafil DBPC and OL EOT to approximately 90% (penetration) and 80% (intercourse success) vs. 61% (penetration) and 39% (intercourse success) for DBPC placebo. At sildenafil DBPC and OL EOT, > or = 90% of men were taking sildenafil 100 mg. Sildenafil was generally well tolerated.. In this trial of men with ED and BPH-associated LUTS, sildenafil treatment for ED was efficacious, effective and generally well tolerated.

Topics: Aged; Double-Blind Method; Erectile Dysfunction; Humans; Male; Middle Aged; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Prostatism; Purines; Quality of Life; Self Concept; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome

To investigate the effect of sildenafil on uroflowmetry values of patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic enlargement (BPE).. Thirty-eight consecutive patients and 15 control subjects without voiding symptoms were enrolled in the study. All patients underwent uroflowmetry testing thrice on different occasions. The highest maximum urinary flow rate (Q(max)) values with a sufficient voided volume (> or =150 ml) were evaluated. The patients and controls were seen the day after the initial uroflowmetry measurements and were given 100 mg sildenafil. Afterwards uroflowmetry was repeated. The uroflowmetry values of both groups before and after sildenafil were compared.. Of the 38 patients, 29 (76%) showed improvement in flow rates. The mean Q(max) was 11.4 +/- 0.39 and 15.7 +/- 0.74 ml/s before and after sildenafil, respectively (p < 0.0001). The mean percentage difference in Q(max) was +38% higher after sildenafil. The mean average flow rate (Q(ave)) and the mean voiding time values were also significantly improved. The mean voided volumes of the patients before and after sildenafil were 241 +/- 78 and 264 +/- 72 ml, respectively (p = 0.07). There were no significant differences in the Q(max), Q(ave) and voided volumes of the control group.. Sildenafil exhibits a significant improvement in Q(max) and Q(ave) rates in men with LUTS.

Topics: Aged; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Pilot Projects; Piperazines; Prostatic Hyperplasia; Prostatism; Purines; Sildenafil Citrate; Sulfones; Urodynamics

To evaluate the potential of sildenafil, vardenafil and tadalafil, all phosphodiesterase-5 (PDE-5) inhibitors used for treating erectile dysfunction, for treating benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).. The mRNA expression of the PDE-5 was determined in rat LUT tissues. The PDE-5 inhibitors were also tested in organ-bath experiments and in a partial bladder outlet obstruction (BOO) rat model in vivo.. The highest PDE-5 mRNA expression was in the bladder, followed by the urethra and prostate. PDE-5 inhibitors dose-dependently reduced the contraction of the isolated bladder, urethral and prostate strips. The rank order of potency was vardenafil > sildenafil > tadalafil. In human prostate stromal cells vardenafil inhibited cell proliferation and was more effective than tadalafil and sildenafil. In the BOO model, there was a reduction in the non-voiding contractions after bolus intravenous administration of 3 mg/kg sildenafil and vardenafil.. These results show that PDE-5 is expressed in LUT tissues. PDE-5 inhibitors induced significant relaxation of these tissues, inhibited the proliferation of human prostate stromal cells and reduced the irritative symptoms of BPH/LUTS in vivo. Therefore, PDE-5 inhibitors could be used as an effective treatment for BPH/LUTS.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Carbolines; Cyclic Nucleotide Phosphodiesterases, Type 5; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Prostatism; Purines; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

To examine the relationship of 'symptom flare' with sexual function and lower urinary tract symptoms (LUTS) before brachytherapy, as we noted that after brachytherapy for prostate cancer, some patients had recurrent LUTS after an asymptomatic period; this secondary exacerbation of symptoms ('symptom flare') occurred at approximately 2 years after implantation and was transient in most patients.. In all, 854 patients with organ-confined prostate carcinoma had transrectal ultrasonography-guided transperineal 125I interstitial brachytherapy of the prostate gland between June 1991 and September 2002, and were considered candidates for this study. Detailed information on urinary function was self-administered and prospectively collected before treatment and at intervals using the International Prostate Symptom Score (IPSS). Sexual function was evaluated with the Sexual Health Inventory for Men (SHIM), a five-question, self-administered diagnostic test that can help to indicate the presence or absence of erectile dysfunction (ED). We used previously established criteria to estimate the risk of prostate-specific antigen (PSA) failure by dividing the men into three risk groups, i.e. low-risk, with a PSA level of < or = 10 ng/mL, stage < or = T2a, Gleason < or = 6; medium-risk, with a PSA level of < or = 15 ng/mL, Gleason 7 or stage T2b; and high-risk, with a PSA level of > 15 ng/mL, stage > T2b, or Gleason > or = 8.. There was a significant association of flare with ED; men with flare reported significantly more ED than men without (P = 0.020). Men with high-risk disease reported more ED because they received more intensive treatment (hormones and increased radiation dose) than men with medium- or low-risk disease. To correct for this confounding factor, multivariate linear regression was used; the regression was significant overall (P < 0.001), and the effects of risk group (P < 0.001) and flare (P < 0.026) on SHIM score were significant and independent of each other. Flare was also significantly associated with a higher pre-implant IPSS; the probability of flare was 62% for a pre-implant IPSS of zero, to 94% for an IPSS of 30.. Radiation reaction and radiation sensitivity contribute to ED and greater LUTS in men who have had brachytherapy for prostate cancer. This contribution is evident, e.g. in men with ataxia-telangiectasia (ATM) gene mutations. Sequence variants in the ATM gene, particularly those that encode for an amino-acid substitution, are associated with adverse radiotherapy responses among patients treated with 125I prostate brachytherapy. Our finding of the association of urinary symptom flare with ED suggests it would be worthwhile to determine whether sildenafil is as effective in men with flare, and if not, whether higher sildenafil doses would be of value. Alternatively, alpha1-selective adrenoceptor-blocking agents, e.g. terazosin, combined with sildenafil, might be of benefit. Also, patients with a high IPSS before brachytherapy can be warned that they have a greater risk of flare and ED.

Topics: Aged; Brachytherapy; Erectile Dysfunction; Humans; Male; Mutation; Piperazines; Prostatic Neoplasms; Prostatism; Purines; Quality of Life; Radiation Tolerance; Recurrence; Risk Factors; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents