Safety and efficacy of alprostadil sterile powder (S. Po., CAVERJECT) in diabetic patients with erectile dysfunction

OBJECTIVES: To evaluate the long-term efficacy and safety of intracavernosal alprostadil (CAVERJECT((R))) in diabetic patients with erectile dysfunction (ED). PATIENTS AND METHODS: This study included 31 diabetic men (aged 44-75 years) with ED of >/=4 months duration. All patients were initially instructed in the self-injection technique at the investigator's clinic. The optimal dose was determined for each patient and set at one of the following: 5, 10, 20, 30, 40, 50, or 60 microg. After the optimal dose was determined and the patient was well trained, the self-injection home phase was followed for 6 months. The efficacy and adverse events were documented. RESULTS: An optimal dose was determined for 29 men (93.5%) and in 16 men (55%) it was >/=20 microg. During the home phase, 76.5% of injections assessed by the patients resulted in satisfactory sexual activity and 72.5% of injections assessed by partners resulted in satisfactory intercourse. A total of 16 patients dropped out during the titration phase (n = 2) and the home phase (n = 14). The most common reasons included lack of efficacy (n = 3, all in the home phase), intolerable penile pain (1 in the titration phase, 2 in the home phase) and dissatisfaction with the higher dosage (n = 2). Penile pain occurred in 19 (61%) of 31 patients. Most were tolerable, and the incidence decreased with time. Prolonged erection occurred in 2 men (6.5%), and no priapism was noted. Penile fibrosis occurred in 1 patient (3. 2%). None of the systemic medical events were related to the study mediction. However, 1 patient suffered from right putaminal hemorrhage in the last month, and this was considered to be caused by underlying hypertension and not drug-related. CONCLUSION: Despite the high incidence of penile pain, most of the occurrences were tolerable. Despite a higher withdrawal rate in this study, intracavernosal alprostadil is still considered as a relatively effective and safe treatment in some diabetic patients with ED if the individual dose is established by titration and patients are trained in the self-injection technique with period supervision.     

Multicenter study of the treatment of erectile dysfunction with transurethral alprostadil (MUSE) in Korea

A Korean multicenter study was conducted to assess the effectiveness of transurethral alprostadil with MUSE in 334 subjects with chronic erectile dysfunction (ED) who were enrolled in 21 clinical centers. Patients with psychogenic impotence comprised about 30% of subjects. Intraurethral alprostadil was titrated in a stepwise fashion in the clinics from 250 to 500 or 1000 mcg based on erectile response and tolerability. The erectile responses were evaluated using an erection assessment scale (score of 1-5). The dose that produced a maximal penile response of score 5 (full rigid erection) or 4 (full tumescence, partial rigidity) was selected for home treatment. Patients who showed partial erection (score of 3) with 1000 mcg were also included in the home-treatment group. In-clinic phase: 198 men (59.3%) had maximal penile responses of score 4 or 5. The rate of maximal responses was not related to patient age, etiology or duration of the ED. A total of 228 (68.3%) men progressed to home treatment. The overall level of comfort of the transurethral alprostadil was rated as uncomfortable or very uncomfortable in 12%. Home phase: During the two-month period of home treatment, 178 (78.1%) men had successful sexual intercourse at least once, and 78.2% of administrations (1976) resulted in successful intercourse. The main causes of drop-out were insufficient erectile response in 27 men (11.8%), adverse reactions (mostly penile or urethral pain) in 7 (3.1%) or both in 7 (3.1%). In conclusion, transurethral alprostadil could be a suitable treatment option for patients with ED regardless of age and etiology of ED. Efficacy in an Asian population (Korea) is comparable to that reported previously in Caucasians.     

Evaluation of transurethral application of alprostadil for erectile dysfunction in Indonesians

Aim: To evaluate the efficacy and safety of transurethral application of alprostadil (MUSE.) for the treatment of erectile dysfunction in Indonesians. Methods: Twenty erectile dysfunction patients aged between 32 - 74 years old were recruited in this study. The inclusion criteria were as follows: 1 ) adult males 18 years or older with a subjective complaint or erectile dysfunction, 2) to provide written informed consent, 3) to agree not to use other forms of treatment for erectile dysfunction, 4) fulfill the screening laboratory values. Part 1, eligible patients were titrated in the clinic starting with a dose of 250 μg and proceed in a stepwise manner to 500μg and 1000μg on separate clinic visits until they identified a dose that produced a satisfactory response. The interval between each in-clinic titration was 2-3 days. Each in-clinic titration dose was evaluated at 15 min intervals over a one hour period for erection assessment, blood pressure and pulse. Part 2, patients used MUSE at home for three months at the dose identified during the inclinic titration. Monthly interim visits were required for patient follow-up and drug distribution. At the end of the study, patients had another laboratory (except testosterone, only assayed in screening procedure) and physical examination. Results: The etiology of erectile dysfunction was psychological in 5 patients and organic in 15 patients. The 65% of the patients achieved the erection scale of 4 or 5 either in the clinic or at home, 10% achieved the scale of 4 at home, but not in the clinic, and 25 % only achieved the scale of 2 or 3 with the highest dose of 1000μg either in the clinic or at home. No significant differences were found in biochemical examination before and after the study. The 60 % of the patients who achieved erection scale 4 or 5 continued to use MUSE until the end of the study, while 40 % of them complained of pain at the time of MUSE application, during erection and/or during intercourse. They withdrew from the study. Conclusion: Transurethral application of alprostadil (MUSE) is effective and safe to produce erection sufficient for intercourse in erectile dysfunction of various etiologies. Pain during application, erection and intercourse is a common side effect and a cause of withdrawal.     

ERECTILE RESPONSE TO TRANSURETHRAL ALPROSTADIL, PRAZOSIN AND ALPROSTADIL-PRAZOSIN COMBINATIONS

Purpose

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.

Materials and Methods

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 8.15 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.

Results

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 micro g.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 micro g.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p <0.001). The 500/2,000 micro g. 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 micro g.). However, combinations of 125/500 and 250/500 micro g. alprostadil/prazosin were more effective (p <0.01) than 125 and 250 micro g. 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.

Conclusions

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.     

Axial penile rigidity as primary efficacy outcome during multi-institutional in-office dose titration clinical trials with alprostadil alfadex in patients with erectile dysfunction. Alprostadil Alfadex Study Group

The purpose of the study was to utilize axial penile buckling testing as a primary efficacy variable of erection quality during multi-institutional in-office dose titration testing with alprostadil alfadex, prostaglandin E1 (PGE1)-alpha-cyclodextrin, (EDEX /VIRIDAL, Schwarz Pharma) in patients with erectile dysfunction. In 41 study sites, in three different dose titration studies involving 894 patients with impotence >6 months, a buckling test was performed and repeated every 10 min for up to 60 min, within 30 min following alprostadil alfadex administration, or when two consecutive circumference measurements reached maximum values. The buckling device consisted of a standard weight scale attached to a 2 inch diameter plastic cap with a concavity on its ventral surface (H. Eric Richards, Inc., Canton MA). A positive test was associated with absent penile shaft buckling to a downward force of 1.0 kg, slowly applied to the glans in the axis of the erect shaft. A total of 630 (71%) patients experienced at least one positive buckling test. Three consecutive positive buckling tests, implying a functionally rigid erection for at least 20 min, were noted in 521 (58%) patients. There were high correlations between the presence of three consecutive positive buckling tests following alprostadil alfadex injection and the patient's (83% of cases) and the investigator's (88% of cases) evaluation of adequacy of erection for intercourse. Similarly, there were high correlations between the presence of negative buckling tests and the patient's (95% of cases) and the investigator's (96% of cases) evaluation of inadequacy of erection for intercourse. The axial penile buckling test offers a simple, reliable, and inexpensive method to objectively quantify erectile response following in-office dose titration of intracavernosal alprostadil alfadex. The high correlation to subjective patient/investigator assessment adds to the validity of the test.     

EFFICACY AND SAFETY OF TRANSURETHRAL ALPROSTADIL IN PATIENTS WITH ERECTILE DYSFUNCTION FOLLOWING RADICAL PROSTATECTOMY

Purpose

A retrospective analysis of the MUSE* clinical trial was performed to evaluate the efficacy and safety of transurethral alprostadil in patients with erectile dysfunction after radical prostatectomy.

Materials and Methods

Patients received doses of transurethral alprostadil in the clinic and those for whom a suitable dose was determined were treated at home with active drug or placebo for 3 months. Patients had undergone radical prostatectomy no less than 3 months before study entry.

Results

Of the 384 patients in whom radical prostatectomy was identified as a cause of erectile dysfunction 70.3% had an erection believed sufficient for intercourse in the clinic and 57.1% on active medication had sexual intercourse at least once at home. The product of clinic and home success rates (70.3 x 57.1%) was an overall success rate (the likelihood of active treatment to lead to intercourse at home) of 40.1%. The frequency of most adverse effects of radical prostatectomy was comparable to that of other organic etiologies of erectile dysfunction (1,127 patients). The percentage of patients with hypotension in the clinic was lower after radical prostatectomy compared to other erectile dysfunction etiologies (0.8 versus 4.2%, p <0.001) but the percentage of patients with urethral pain/burning was higher (18.3 versus 10.4%, p = 0.027). No urinary tract infection, fibrosis or priapism occurred in the post-radical prostatectomy patients.

Conclusions

Transurethral alprostadil is a well tolerated and efficacious method of treating erectile dysfunction after radical prostatectomy, although psychological changes associated with cancer and surgery may limit home response. The severe neurovascular deficit associated with prostatectomy neither limits the efficacy of transurethral alprostadil nor increases the risks.     

Optimizing the therapeutic approach of transurethral alprostadil

OBJECTIVE: To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 microg and 500 microg, MUSE, Vivus Inc., Menlo Park, CA, USA, and Astra L?kemedel AB, S?dert?lje, Sweden) and the need for dose titration in a general population with erectile dysfunction. PATIENTS AND METHODS: In a 12-week randomized and open multicentre study with parallel groups, 166 patients were randomised to a starting dose of either 250 or 500 microg of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 microg) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attained. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. RESULTS: The lowest dose of MUSE with which the patients achieved at least one EAS score of 4 or 5 was 125 microg for 1% of participants, 250 ++microg for 27%, 500 microg for 32%, 1000 microg for 6%, and finally 1000 microg plus a pubic band for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients (> 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 microg). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least once in course of the study. More patients reported penile pain while treated with 500 microg than with 250 microg (P < 0.05) during the first 4 weeks. However, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the clinic or at home. CONCLUSION: Recommending 500 microg as a starting dose increased the percentage of patients reporting at least one EAS of 4-5, with or without sexual intercourse, from 28% to 60%. No serious dose-related systemic effects were seen. When starting on 500 microg, patients were more likely to find directly the dose that gave sufficient response and treatment satisfaction. We suggest that the appropriate starting dose of MUSE should be 500 microg.     

A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil

Objectives

Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder.

Methods

This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses ( 125, 250, 500, and 1000 μg) and placebo over a 2 to 4 week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration.

Results

Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1 % to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study.

Conclusions

Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction.     

Potentiation of erectile response and cAMP accumulation by combination of prostaglandin E1 and rolipram, a selective inhibitor of the type 4 phosphodiesterase (PDE 4).

PURPOSE: Phosphodiesterases (PDEs) are an important component of the signal transduction pathway during the erectile response. To determine the PDE isoforms in the corpora cavernosa in the cat and to establish the functional presence of PDE 4 in human cavernosal tissue, the erectile response to intracavernosal phosphodiesterase (PDE) inhibitors alone and the combination of PDE inhibitors and prostaglandin E1 (PGE1) was evaluated in the anesthetized cat. The in vitro formation of cAMP and cGMP in human cavernosal smooth muscle cells (HCSMCs) treated with PGE1 and rolipram in primary culture was also measured. MATERIALS AND METHODS: In pentobarbital-anesthetized cats, increases in intracavernosal pressure, penile length, and duration of erectile response were determined after intracavernosal injections of (i) the type 3 cAMP-specific, cGMP-inhibitable PDE inhibitor, milrinone, (ii) the type 4 cAMP-specific PDE inhibitor, rolipram, (iii) the type 5 cGMP-specific PDE inhibitor, zaprinast, and (iv) the combination of rolipram and PGE1. Systemic arterial pressure was concurrently assessed in these experiments. All responses to PDE inhibitors were compared with a control triple-drug combination comprised of papaverine (1.65 mg.), PGE1 (0.5 microg.), and phentolamine (25 microg.). HCSMCs were incubated with PGE1 (3 microM) and rolipram (10 microM) individually or in combination up to 2 hours at 37C. The intracellular cAMP and cGMP was extracted by cold absolute ethanol and measured (pmol./10(6) cells) by a commercially available EIA kit. RESULTS: Milrinone (3 to 100 microg.), rolipram (3 to 100 microg.), and zaprinast (3 to 100 microg.) induced dose-dependent increases in intracavernosal pressure and penile length (p <0.05) when administered intracavernosally. The maximum increase in cavernosal pressure in response to zaprinast was associated with no significant change in systemic arterial pressure. When rolipram was combined with PGE1 (0.1 microg.), the increases in intracavernosal pressure and the duration of erectile response were significantly higher (p <0.05) and longer (p <0.05) than those observed when rolipram alone was injected intracavernosally. PGE1 (3 microM) and rolipram (10 microM) produced significant increases (p <0.05) in the accumulation of intracellular cAMP levels in HCSMCs in primary culture above those of the baseline values while intracellular levels of cGMP did not change. CONCLUSIONS: PDE inhibitors administered intracavernosally caused dose-dependent increases in cavernosal pressure in the cat. When a specific cAMP PDE inhibitor was combined with PGE1, the erectile response was enhanced and intracellular levels of cAMP were increased in HCSMCs in primary culture. These data suggest further exploration of the combination of various PDE inhibitors and PGE1 in the pharmacologic treatment of erectile dysfunction and provide functional evidence for the presence of PDE 4 isoenzyme in human penile cavernosal cells.     

Efficacy and safety of intracavernosal alprostadil alfadex in the treatment of erectile dysfunction

Background Prostaglandin E₁ (PGE₁) is well established as an effective treatment for erectile dysfunction with at least 70% and up to 100% of patients achieving erections adequate for sexual intercourse.
Methods This multicentre, open-label, non-controlled study of intracavernosal alprostadil alfadex (up to 20 μg) was conducted in the UK in 123 male patients with erectile dysfunction for at least 6 months. Following a screening and in-office titration period (period 1) patients entered a 6–10-week self-injection home-treatment phase (period 2) followed by a 34–38-week follow-up period (period 3). A patient was considered to be a `responder' if he had erections adequate for sexual intercourse with at least 75% of injections. Secondary measures of efficacy included clinical assessment of erection using a five-grade scale and Buckling Test.
Results A total of 106 patients entered the titration period. In period 2, 72% of patients were responders and 77% of injections resulted in an erection adequate for sexual intercourse. According to the five-grade scale, 73% of patients gained an optimal response and 48–79% of patients were found to have a positive Buckling Test, both during period 1. During follow up (period 3), 83% of patients were responders. There were a total of 403 penile pain events related to the study drug procedure; almost all were rated as mild (49%) or moderate (49%). Only two patients discontinued treatment owing to pain. Couples reported that the treatment was easy to use, with 81% of patients rating the treatment as good to excellent.
Conclusions Alprostadil alfadex is effective, well tolerated and easy to use.     

Effects of moxonidine and metoprolol in penile circulation in hypertensive men with erectile dysfunction: results of a pilot study

Centrally acting (moxonidine) and peripherally acting (metoprolol) sympatholytic agents might have different actions upon penile circulation in hypertensive men with erectile dysfunction. A total of 11 nonsmoking, hypertensive but otherwise healthy men with erectile dysfunction were studied after 8 weeks on moxonidine monotherapy (0.4 mg per day, increased to 0.6 mg if needed) and then after 8 weeks of metoprolol monotherapy (100 mg per day, increased to 200 mg if needed) in a crossover design. At the end of each treatment phase, the subjects were asked about their subjective erectile capacity (nocturnal and coital erections), and resting and stimulated (after intracavernosal injection of a mixture of alprostadil and phentolamine) penile deep artery diameters and systolic peak velocities were measured by color Doppler ultrasonography. There were no significant differences in blood pressure after either therapy. The change from earlier antihypertensive therapy, moxonidine produced significant subjective amelioration of sexual dysfunction in 9/11 of the men (< or = 0.001), whereas 9/11 returned to impaired dysfunction after crossover to metoprolol treatment. Resting and stimulated deep penile diameters and peak systolic velocities were higher after moxonidine treatment compared with metoprolol (diameters: < or = 0.004, < or = 0.0001; velocities: < or = 0.008, < or = 0.038). The centrally acting sympatholytic agent moxonidine seems to improve erectile function both subjectively and objectively and has a better effect on penile circulation compared with the peripherally acting sympatholytic agent metoprolol.     

HEMODYNAMIC EFFECTS OF TRANSURETHRAL ALPROSTADIL MEASURED BY COLOR DUPLEX ULTRASONOGRAPHY IN MEN WITH ERECTILE DYSFUNCTION

Purpose

We evaluated the hemodynamic effects of transurethral alprostadil in 21 patients with erectile dysfunction using color duplex ultrasonography.

Materials and Methods

Penile arterial diameter, peak flow velocity and end diastolic velocity were compared following intraurethral administration of 500 micro g. alprostadil and intracavernosal injection of 10 micro g. alprostadil.

Results

A dose of 500 micro g. transurethral alprostadil resulted in significant increases in corporeal blood flow comparable to those achieved with intracavernosal injection of 10 micro g. 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.

Conclusions

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.     

Efficacy of vardenafil and sildenafil in facilitating penile erection in an animal model

Vardenafil and sildenafil are potent and specific phosphodiesterase type 5 (PDE 5) inhibitors. In human penile cavernosal smooth muscle cells, we have previously shown that vardenafil has a lower biochemical inhibition constant (Ki) than sildenafil. In this study, we compared the efficacy of vardenafil and sildenafil in facilitating penile erection in a rabbit model. Penile erections were elicited by submaximal (2.5 or 6 Hz) pelvic nerve stimulation (PNS) repeated every 5 minutes for 30 minutes with or without intravenous (i.v.) administration of vardenafil (1-30 microg/kg) or sildenafil (10-30 microg/kg). Erectile response was assessed by continuously recording intracavernosal pressure (ICP) and systemic arterial pressure (SAP). All data were expressed as a ratio of ICP:SAP. I.v. administration of either PDE 5 inhibitor facilitated PNS-induced erection and increased ICP:SAP in a dose-dependent manner, reaching peak response at approximately 5 minutes. However, the threshold dose at which facilitation of erection occurred was lower for vardenafil (3 microg/kg) than for sildenafil (10 microg/kg). At the 10-microg/kg dose (i.v.), the response duration was significantly greater with vardenafil (169 +/- 23 seconds) than with sildenafil (137 +/- 31 seconds). Direct intracavernosal (i.c.) injection of 1-30 microg/kg vardenafil or sildenafil also caused dose-dependent increases in ICP:SAP in the absence of PNS. Response durations increased in a dose-dependent manner and lasted more than 5 times that of i.v. drug administration coupled with PNS. Irrespective of the route of administration (i.c. or i.v.), at equivalent doses, vardenafil was significantly more efficacious than sildenafil in facilitating pelvic nerve-mediated penile erection and in eliciting erection in the absence of PNS. The increases in ICPs occurred more quickly, were of larger magnitude, and were sustained for longer durations for vardenafil than for sildenafil. On the basis of the biochemical data and physiological responses from this study, further clinical evaluation of vardenafil as treatment for erectile dysfunction is warranted.     

Peyronie＇s disease： a silent consequence of diabetes mellitus

Aim： To investigate the clinical characteristics of patients with Peyronie＇s disease （PD） and diabetes mellitus （DM）. Methods： During an 8-year period, a total of 307 men seen at our outpatient clinic were diagnosed with PD. Clinical characteristics, penile deformities and the erectile status of patients with PD and DM together （n = 102） were retrospectively analyzed and compared to patients with PD alone with no risk factors for systemic vascular diseases （n = 97）. Results：The prevalence of PD among men with DM and sexual dysfunction was 10.7 %. The mean age of diabetic patients with PD was （55.9 ± 8.9） years; in the no risk factor group it was （48.5 ± 9.0） years （P 〈 0.05）. The median duration of DM was 5 years. The majority of diabetic patients with PD （56.0 %） presented in the chronic phase （P 〈 0.05）, and they were more likely to have a severe penile deformity （〉 60°） than the no risk factor group （P 〈 0.05）. In the diabetic group, the most common presenting symptom was penile curvature （81.4%）, followed by a palpable nodule on the shaft of the penis （22.5%） and penile pain with erection （14.7%）. A total of 19.6% of patients were not aware of their penile deformities in the diabetic group. Erectile function, provided by history and in response to intracavernosal injection and a stimulation test, was significantly diminished in patients with PD and DM （P 〈 0.05）. Conclusion： DM probably exaggerates the fibrotic process in PD. Diabetic patients with PD have a higher risk of severe deformity and erectile dysfunction （ED）. PD seems to be a silent consequence of DM and should be actively sought in diabetic men. （Asian JAndrol 2006 Jan; 8： 75-79）     

Clinical experience with intraurethral alprostadil (MUSE) in the treatment of men with erectile dysfunction. A retrospective study. Medicated urethral system for erection

OBJECTIVE: The Food and Drug Administration (USA) approved the transurethral administration of prostaglandin (alprostadil in January 1997), which had an efficacy of approximately 50% in clinical trials. We studied its effectiveness in clinical practice. METHODS: Patient and partner education was followed by an initial office trial of a medicated urethral system for erection (MUSE) after other medical risk factors were corrected during a 2- to 4-month period. The initial titration dose of alprostadil was usually 125 or 250 microg. Further titration, if needed, was instituted by the patient at home. Success was determined as the satisfactory completion of sexual intercourse in more than 66% of attempts, with a minimum of two being required. RESULTS: Two hundred and seventy patients entered the trials, and follow-up information was available in 229 (85%). The overall success rate was 56%. The dose required was 500 microg in 49.2% and 1,000 microg in 42.2%. Of the 44% in whom treatment failed, 61.4% did so because of lack of efficacy and 38.6% because of side effects (genital pain or urethral bleeding). Minor urogenital symptoms, which did not interfere with treatment, occurred in an additional 40% of patients. CONCLUSIONS: The efficacy of transurethral administration of alprostadil (56%) is higher than the initial published clinical trial data and higher than recent reported clinical experiences, although higher doses were required in our study. Men over 50 years of age, having an organic cause for erectile dysfunction, had better responses. Patient and partner education is important for successful treatment, and the in-office initial titration is an integral part of this success. Prior correction of medical risk factors may enhance the success rate.     

Results from different patient populations using combined therapy with alprostadil and sildenafil: predictors of satisfaction

OBJECTIVE: To evaluate the outcome of combined therapy (using intraurethral alprostadil and oral sildenafil) in private and clinic patients with erectile dysfunction, and thus assess predictors of satisfaction. PATIENTS AND METHODS: In all, 360 men were treated for erectile dysfunction using single and/or combined therapy, comprising 214 private-practice and 166 clinic patients. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Serum testosterone levels, education and socio-economic status were also assessed. Group 1a consisted of 33 private patients and Group 1b of 24 clinic patients who tried the maximum dose of intraurethral alprostadil monotherapy initially, followed by the maximum dose of sildenafil monotherapy, and remained dissatisfied. Group 2a consisted of 32 private patients and group 2b of 31 clinic patients who tried the maximum dose of sildenafil monotherapy initially, followed by the maximum dose of alprostadil monotherapy, and were also dissatisfied. These two groups of 65 private and 55 clinic patients then underwent combined therapy. RESULTS: The mean (SD) score for erectile function was 24.1 (2) for combined therapy (a 123% improvement), and 19.8 (1. 8) (83% improvement) and 15.2 (1.6) (41% improvement) for sildenafil and alprostadil monotherapies (P < 0.05 for both patient groups). The men also reported an improvement in their satisfaction with intercourse. However, at 18 months, 60 of the 65 private patients but only 40 of the 55 clinic patients continued with combined therapy; thus, the discontinuation rate was three times greater among clinic than among private patients. Furthermore, the private patients had an overall improvement in the satisfaction score of 128%, compared with 51% for the clinic patients. CONCLUSION: Although there were no significant differences in erectile function improvement within the two satisfied combined therapy groups, the differences in overall satisfaction and long-term withdrawal rates suggests that other factors beside motivation must be involved for success, e.g. education, persistence, realistic expectations, and certain psychological factors. Combined therapy should be considered for those patients who have a suboptimal response to monotherapy and refuse or are not candidates for surgical options. Generally, those patients with a higher education, greater persistence and more realistic expectations were more satisfied with combined therapy.     

Intraurethral application of alprostadil in patients with failed inflatable penile prosthesis

PURPOSE: Many men who underwent penile prosthesis implantation before the advent of oral and injection therapy present for replacement of a malfunctioning prosthesis but choose not to undergo revision surgery because of personal, medical or reimbursement issues. Others with normally functioning prostheses report significant difficulties with "cold glans," and they and their partners observe decreased engorgement and temperature of the glans penis with the inflated penile prosthesis, despite adequate stimulation. Intracorporal injection therapy is contraindicated in any patient with a penile prosthesis and use of a vacuum erection device may result in prosthesis cylinder rupture. In these patients intraurethral application of alprostadil may restore prosthesis function and permit satisfactory intercourse. We evaluate the efficacy of a medicated urethral system for erection (MUSE) using alprostadil to restore function for men with a failed prosthesis, and improve glans penis temperature sensation and engorgement for those with a functioning prosthesis. MATERIALS AND METHODS: From February 1997 to February 1998, 28 men 47 to 81 years old (mean age 61.2) with a penile prosthesis were treated with alprostadil. Of the patients 11 had penile prosthesis failure (group 1) and 17 reported decreased glans penis engorgement (group 2). In 18 cases erections were observed at the clinic. Doses of alprostadil varied from 250 to 1,000 microgm. (mean 566). RESULTS: Of the 28 patients 23 had a response to alprostadil. Erections were sufficient for intercourse in 7 of 11 group 1 patients, and 10 of 17 group 2 were satisfied with treatment. There was no device specific morbidity but 12 men discontinued use of alprostadil because of penile pain. A significant or excellent response was noted in 10 of 18 men observed at the clinic. CONCLUSIONS: Intraurethral alprostadil may be used to restore or improve function of a penile prosthesis in patients with a malfunctioning device or lack of glans penis engorgement, with low expected morbidity.     

Initial results utilizing combination therapy for patients with a suboptimal response to either alprostadil or sildenafil monotherapy

OBJECTIVE: Intraurethral alprostadil and oral sildenafil are useful in selected patients. However, there continues to be a significant treatment failure rate. Since their mechanisms of action are different, we wanted to evaluate the effectiveness of combination therapy. MATERIALS AND METHODS: Of 214 patients treated for erectile dysfunction (ED), 65 were not fully satisfied with the firmness of their erections via monotherapy. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Group I consisted of 33 patients who tried maximal dose intraurethral alprostadil monotherapy initially, followed by the maximal dose of sildenafil monotherapy, and were still unsatisfied. Group II consisted of 32 patients who tried the maximal dose sildenafil monotherapy initially, followed by the maximal dose of alprostadil monotherapy, and were also unsatisfied. There 65 patients then underwent combination therapy. RESULTS: 60 out of the 65 patients stated they were satisfied with combination therapy. Questionnaire scores for erectile function were 23.1+/-2.0 (114%) for combination therapy vs. 19.2+/-1.8 (77%) and 15.2+/-1.6 (41%) for sildenafil and alprostadil monotherapies (p<0.05). There were no significant differences in responses between the two groups. The men also reported improvement in intercourse and overall satisfaction. CONCLUSIONS: Combination therapy may be an option for motivated patients who have a suboptimal response from monotherapy.     

Efficacy of virtual glasses in audio-visual sexual stimulation during penile color duplex Doppler ultrasonography

OBJECTIVE: To examine whether audio-visual sexual stimulation (AVSS) with virtual glasses is effective in improving the recording of penile hemodynamics during penile color duplex Doppler ultrasonography. PATIENTS AND METHODS: A total of 64 consecutive patients with erectile dysfunction underwent penile color duplex Doppler ultrasonography after intracavernosal injection of 10-20 microg prostaglandin El and subsequent genital stimulation. AVSS with virtual glasses and earphones was applied when peak systolic velocities (PSV) were less than 35 cm/s or end diastolic velocities (EDV) were more than 5 cm/s. PSV, EDV and the resistive index of both cavernosal arteries were continuously monitored. Clinical erectile response was assessed with visual inspection and manual palpation. RESULTS: AVSS with virtual glasses was performed on 40 of 64 patients. AVSS improved the clinical erectile response in 26 (65%) of 40 patients. Doppler ultrasonography without AVSS identified 11 (27.5%), 5 (12.5%), and 24 (60%) patients with arteriogenic, veno-occlusive, and mixed-type impotence, respectively. However, after real-time AVSS 15 (37.5%), 7 (17.5%), 8 (20%), and 10 (25%) patients demonstrated non-vasculogenic, arteriogenic, veno-occlusive, and mixed-type impotence, respectively. Real-time AVSS improved the Doppler wave forms in 65% of cases. CONCLUSION: AVSS with virtual glasses improves the recording of physiologic erectile response and may be used as a valuable tool during penile color duplex Doppler ultrasonography.     

Effect of radical retropubic prostatectomy on erectile function, evaluated before and after surgery using colour Doppler ultrasonography and nocturnal penile tumescence monitoring

OBJECTIVE: To assess the effect of radical retropubic prostatectomy on erectile function, by evaluating objectively patients' erectile function before and after surgery. PATIENTS AND METHODS: The study comprised 126 patients with clinically localized prostate cancer who were scheduled to undergo radical retropubic prostatectomy. After giving informed consent for the study, 123 patients underwent intracavernosal injection tests, colour Doppler ultrasonography and nocturnal penile tumescence monitoring before and after surgery. RESULTS: From the intracavernosal injection tests and nocturnal penile tumescence monitoring, 21 patients (17%) were evaluated as having normal erectile function before surgery. After radical retropubic prostatectomy, nine (43%) of these 21 potent men had preserved erectile function. In eight patients whose neurovascular bundles were preserved, five were potent after surgery. The cause of erectile function after surgery was a neurogenic disorder in seven and a related vascular disorder in five. CONCLUSION: From objective tests of erectile function on patients scheduled to undergo radical prostatectomy, 17% had normal erectile function. However, even after nerve-sparing radical retropubic prostatectomy, the proportion retaining potency was unsatisfactory. Although a neurological disorder was the main cause of erectile dysfunction after surgery, vascular disorders were also important.