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Purpose: We evaluated the efficacy and safety of tadalafil 20 mg, taken on demand, in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy (BNSRRP). Materials and Methods: This randomized, double-blind, placebo controlled multicenter study consisted of a 4-week treatment-free run-in period (baseline) followed by 12 weeks of treatment. A total of 303 men (mean age 60 years) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were randomized (2:1) to tadalafil (201) or placebo (102). The 3 co-primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score, and the percentage of positive responses to Sexual Encounter Profile questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary end points. We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence, defined as 50% or greater "yes" responses to Sexual Encounter Profile question 1 (ability to achieve at least some erection) during baseline intercourse attempts and stratified randomization based on this criterion. Results: Patients receiving tadalafil reported greater improvement on all primary and secondary end points (p < 0.001) compared to placebo. For all randomized patients and for the subgroup with evidence of postoperative tumescence, the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil (mean +/- SEM 5.3 +/- 0.5 and 5.9 +/- 0.7, respectively, p < 0.001 vs placebo for both). For all randomized patients who received tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence these values were 69% and 52%, respectively. Of all patients randomized to tadalafil 62% and of the subgroup patients randomized to tadalafil 71% reported improved erections. Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo. Headache (21%), dyspepsia (13%) and myalgia (7%) were the most commonly reported adverse events. Conclusions: Tadalafil 20 mg, taken on-demand, was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP.

We evaluated the hemodynamic effects of transurethral alprostadil in 21 patients with erectile dysfunction using color duplex ultrasonography.Penile arterial diameter, peak flow velocity and end diastolic velocity were compared following intraurethral administration of 500 microg. alprostadil and intracavernosal injection of 10 microg. alprostadil.A dose of 500 microg. transurethral alprostadil resulted in significant increases in corporeal blood flow comparable to those achieved with intracavernosal injection of 10 microg. alprostadil as measured by duplex ultrasonography in men with erectile dysfunction. Transurethral alprostadil resulted in statistically significant increases in arterial diameter and peak flow velocity comparable to those achieved with intracavernosal injection. End diastolic velocities were higher after transurethral alprostadil than intracavernosal injections. Color ultrasonography following transurethral alprostadil showed arterial and venous hyperemia of the corpus spongiosum and corpora cavernosa. Furthermore, color ultrasonography revealed communicating vessels between the corpus spongiosum and corpora cavernosa following administration of transurethral alprostadil.The visualization of communicating vessels between the corpus spongiosum and corpora cavernosa after transurethral alprostadil suggests local mechanisms of drug transfer from one to the other. In addition to potential clinical benefits, transurethral alprostadil may be useful to visualize the vascular anatomy of the penis and to test for patient responsiveness to local vasoactive agents.

Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder.In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales.Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination.Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.

We established hemodynamic predictors of response to intracavernous pharmacotherapy.Specific characterization and quantification of hemodynamic abnormalities of the cavernous arterial inflow and corporeal veno-occlusive mechanism associated with failure to respond to intracavernous pharmacotherapy were performed retrospectively in 69 patients with nonendocrinological impotence. We investigated atherosclerotic vascular risk factors, duplex ultrasonography peak systolic and end diastolic velocities (10 micrograms. prostaglandin E1), and dynamic infusion cavernosometry and cavernosography parameters (60 mg. papaverine and 6 mg. phentolamine).The patients were stratified by severity of the various hemodynamic parameters encountered and mean dose required for response. Response subsequently was characterized as excellent (75% or greater rigid erections) in 36 patients, adequate (erections sufficient for intromission) in 17 and poor or absent in 16. Psychogenic, neurogenic and mild vasculogenic causes were noted in patients with an excellent response. The adequate responses included all 3 cases with mild to moderate vascular etiologies whereas patients with a poor or no response had only severe venogenic and combined arteriogenic and venogenic etiologies. Mean flow-to-maintain values plus or minus standard deviation of 9.7 +/- 3.7, 10.8 +/- 9.5 and 59.5 +/- 24.2 ml. per minute were demonstrated in the excellent, adequate and poor or no response groups, respectively. There was a good correlation between mean flow-to-maintain values and mean doses of our standard vasoactive solution (r2 = 0.88, p0.0001). Pharmaco-cavernosography demonstrated diffuse or pan-cavernous corporeal veno-occlusive dysfunction in the poor or no response group.Corporeal veno-occlusive dysfunction alone or combined with arterial disease is the specific hemodynamic abnormality causing nonresponse to intracavernous pharmacotherapy. Diffuse drainage, particularly involving the glans penis and corpus spongiosum, is greatly predictive of a poor or no response, reflecting the underlying cavernous smooth muscle myopathy and collagen degenerative alterations in these patients with end-organ failure.

The bulk of the parenchyma of the corpora cavernosa consists of bundles of smooth muscle fibers. These bundles are oriented in all directions and establish at least 2 insertions upon elements of the fibrous skeleton of the corpora. The fibrous skeleton includes the tunica albuginea and its fibrous columns, the intracavernous fibrous framework, and the periarterial and perineural fibrous sheaths. The cavernous vascular spaces (sinusoids) form an intercommunicating network embedded within the mass of smooth muscle. Thus, the smooth muscle does not form a muscular wall proper for each sinusoid. (J. Urol., 144: 1144–1146, 1990)