A comparative, crossover study of the efficacy and safety of sildenafil and apomorphine in men with evidence of arteriogenic erectile dysfunction

The aim of the study was to establish and compare the efficacy and safety of sildenafil and apomorphine in men with arteriogenic erectile dysfunction (ED). In all, 43 men with ED and postinjection max penile systolic velocity <25 cm/s in repeated Doppler ultrasonography were included. Of these, 24 men started on apomorphine 2 mg and 19 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg according to effectiveness and tolerability. Safety was evaluated according to adverse events (AEs) and patient withdrawal. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on event log data. The incidence of AEs with apomorphine 3 mg was higher than with sildenafil 100 mg. Two men on apomorphine 3 mg discontinued treatment due to AEs. The overall success rate of sildenafil was 63.7% compared to 32.1% of apomorphine (Pearson chi(2), P<0.01). Of all men, 25 (58.1%) responded to sildenafil 50 mg without the need for dose increase, while only one responded to apomorphine 2 mg. The response to sildenafil 50 mg was age related (analysis of variance, p=0.04). Satisfaction was reported by 76.75 and 13.95% of patients for sildenafil and apomorphine, respectively, but 20.9% were not satisfied with any of the two drugs. In conclusion, this study provides clear evidence that sildenafil, even at 50 mg dose, is more effective than apomorphine 3 mg in men with arteriogenic ED. The fact that one out of five patients is not satisfied with the above-studied drugs shows that new oral agents need to be evaluated for the treatment of this disorder.     

An open-label, randomized, flexible-dose, crossover study to assess the comparative efficacy and safety of sildenafil citrate and apomorphine hydrochloride in men with erectile dysfunction

Two papers in this section deal with well‐known pharmacological agents used to treat male erectile dysfunction. In the first of these, authors from the UK compared the efficacy and safety of sildenafil and apomorphine in such patients. This open‐label crossover trial suggested that sildenafil was better than apomorphine, where the primary endpoint was the erectile function domain of the International Index of Erectile Function. The second paper is an update on the efficacy and safety of tadalafil. It describes the results of its use in a large number of men with erectile dysfunction, compared to placebo. Once again, the erectile function domain was one of the primary endpoints. Tadalafil was an effective and well tolerated treatment for this condition.

OBJECTIVE

To compare the efficacy and safety of sildenafil and apomorphine in the treatment of men with erectile dysfunction (ED).

PATIENTS AND METHODS

In all, 139 men with ED who were naïve to treatment were entered into an open‐label crossover trial with two treatment periods, each of 8 weeks, separated by a 2‐week washout period. Men were randomized to receive either sildenafil then apomorphine or apomorphine then sildenafil, and were allowed to titrate the dose on both drugs. The primary endpoint was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), and other endpoints included diary data, the other domains of the IIEF, overall assessment questions and the Erectile Dysfunction Index of Treatment Satisfaction (EDITS) questionnaire.

RESULTS

The EF domain score after treatment was 25.2 for sildenafil and 15.9 for apomorphine. The treatment difference of the adjusted means was 9.3 points (95% confidence interval 7.6–11.1; P < 0.001). After sildenafil the successful intercourse rate was 75%, vs 35% for apomorphine (P < 0.001), and the EDITS scores were 82.5 for sildenafil and 46.8 for apomorphine (P < 0.001). Of the men, 96% expressed a preference for sildenafil as a treatment for their ED. The side‐effect profiles for both drugs were in keeping with published data.

CONCLUSION

By all measurable endpoints sildenafil was superior to apomorphine in this open‐label crossover study of men with ED who were naïve to therapy

     

Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP

Sildenafil is frequently the first-line treatment for post-radical retropubic prostatectomy (RRP) erectile dysfunction (ED) with maximum treatment satisfaction rates of 43%-80%. The etiology of erectile dysfunction after RRP has been attributed to psychogenic, vascular, veno- occlusive or nerve injury causes. The purpose of this study was to gain insight into the penile duplex Doppler arterial parameters in men with ED after RRP who failed sildenafil. The purpose was to assess whether sildenafil failure after RRP is associated with underlying corporal arterial disease. A total of 174 consecutive men presenting with sildenafil refractory ED after nerve-sparing RRP underwent color duplex penile Doppler evaluation with vasoactive injection. Mean age was 59.6 y and mean time from surgery was 11.6 months. Some 81% (141/174) of the men had no pre-operative ED (PED). Significant differences in penile duplex Doppler parameters for arterial disease were seen between men with and without PED. In men without PED, 19% (27/141) manifested arterial insufficiency. However, in men with PED, 50% (16/33) demonstrated arterial disease. Nerve sparing status did not affect the presence of arterial disease. Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency.     

Comparative cross-over study of sildenafil and apomorphine for treating erectile dysfunction

OBJECTIVE

To compare the effectiveness, safety and tolerability of sildenafil and apomorphine in Brazilian patients with erectile dysfunction (ED) of various causes.

PATIENTS AND METHODS

In all, 108 patients (mean age 55 years, sd 11) and documented ED for ≥6 months were included in 12 centres in Brazil. The patients were initially followed for 2 weeks and then randomized to initial treatment with apomorphine or sildenafil, taken before sexual intercourse, no more than once a day. The initial dose (2 mg apomorphine and 50 mg sildenafil) could be adjusted (to 3 mg apomorphine, or to 25 or 100 mg for sildenafil) depending on the effectiveness and tolerability during the first 4 weeks of treatment. The patients were re‐evaluated after 8 weeks on treatment and, after a wash‐out period of 2 weeks (no treatment), received the other study drug (other than that received in the first phase), and then had the same procedures as in the first phase.

RESULTS

In all, 97 patients were evaluated for therapeutic effectiveness, the overall effectiveness being assessed using two questions; sildenafil had a significantly higher proportion of affirmative answers for both (P < 0.001). Likewise, the estimates for the mean (sd ) proportion of successful sexual intercourse, of 83.3 (4.7)% vs 40.3 (4.7)% and the total ED Inventory of Treatment Satisfaction score, of 86.7 (2.9) vs 56.9 (2.9) (P < 0.001) were higher for sildenafil. At the end of the study, 93.8% of the patients randomized to initial therapy with apomorphine declared a preference for sildenafil, and 81.3% of those initially treated with sildenafil declared a preference for that drug. The two drugs were well tolerated, and the main adverse events for apomorphine were nausea, vomiting, headache, taste perversion and dizziness; for sildenafil they were headache, flushing or vasodilatation, abdominal pain or dyspepsia and nasal congestion.

CONCLUSIONS

Sildenafil is more effective than apomorphine for treating ED, in the domains of erectile function, satisfaction with sexual intercourse and overall satisfaction, and was the drug preferred by most of the patients.     

Different hemodynamic responses by color Doppler ultrasonography studies between sildenafil non-responders and responders

Aim： To determine if there are different penile hemodynamic patterns between sildenafil non-responders and responders by using color Doppler ultrasonography. Methods： A total of 69 erectile dysfunction （ED） patients aged 22-79 years were enrolled into the present study. Thirty-eight （55.1%） men with ED who did not respond to four attempts of treatment with 100 mg sildenafil after re-education were classified as sildenafil non-responders. A com- bination of three vasodilator drugs, 1.25 mg papaverine, 0.4 mg phentolamine and 5 ug prostaglandin E1, was given by intracavernous injection before penile Doppler ultrasonography was carried out. The erectile response to intracavernous injection and vascular parameters including peak systolic velocity （PSV）, resistance index （RI）, end diastolic velocity （EDV） and cavernosa artery diameter （CD） were measured and the results between sildenafil nonresponders and responders were compared. Results： No statistical difference in vascular parameters measured by Doppler ultrasonography studies between non-responders and responders was noted. Sildenafil non-responders had a poorer penile rigidity response to intracavernous injection than responders （P 〈 0.05）. Among patients with adequate PSV （〉 30 cm/s） and abnormal EDV （〉 5 cm/s）, individuals in the non-responder group had fewer positive responses to intracavernous vasodilator injection than in the responder group （35.3% vs. 72.2%, P 〈 0.05）. Advanced age and comorbidity with diabetes mellitus were significantly associated with sildenafil non-response （P 〈 0.05）. Conclusion： Sildenafil non-responders were characterized by a poorer penile rigidity response to intracavernous injection and had an associated impaired veno-occlusive mechanism. Advanced age and comorbidity with diabetes mellitus were two common factors associated with non-response.     

A two-part pilot study of sildenafil (VIAGRA) in men with erectile dysfunction caused by spinal cord injury

STUDY DESIGN: This was a two-part pilot study in men with erectile dysfunction (ED) due to spinal cord injury (SCI: cord level range T6-L5). Part I was a randomised, double-blind, two-way cross-over study comparing a single dose of sildenafil 50 mg or placebo. Part II was a randomised, double-blind, parallel-group evaluation of sildenafil 50 mg or placebo, taken as required (not more than once daily) approximately 1 h prior to sexual activity, over a period of 28 days. OBJECTIVES: To assay the efficacy and safety of sildenafil 50 mg and placebo. SETTING: Clinic- and home-based assessments in the United Kingdom. METHODS: A total of 27 subjects who were able to achieve at least a grade 2 erection (hard, but not hard enough for penetration) in response to penile vibratory stimulation (PVS) were recruited. In Part I, the reflexogenic response of the penis to PVS was evaluated in the clinic while in Part II, the response to treatment was assessed in the home (global efficacy. questionniare, diary). RESULTS: In Part I, 17/26 (65%) subjects had erections of >60% rigidity at the penile base (median duration 3.5 min) after sildenafil compared with 2/26 (8%) (median duration 0 min) alter placebo (P=0.0003). In Part II, 9/12 (75%) subjects on sildenafil and 1/14 (7%) subjects on placebo reported that the treatment had improved their erections (P<0.005), and 8/12 (67%) and 2/13 (15%) men, respectively, indicated that they wished to continue treatment (P<0.02). An analysis of diary data showed no difference between the groups with respect to the mean number of erections hard enough for penetration (P = 0.08). The mean proportion of attempts at sexual intercourse that were successful was 30 and 15%, respectively (P=0.21). Similarly, responses to the end-of-treatment questionnaire indicated that there were no significant differences between the groups with respect to the frequency of erections hard enough for sexual intercourse (P=0.47) or that lasted as long as the subject would have liked (P=0.11). No subject discontinued sildenafil due to adverse events. CONCLUSION: Sildenafil is an effective, well-tolerated oral treatment for ED in SCI subjects.     

Evaluation of the effectiveness of sildenafil using questionnaire methods versus audio-visual sexual stimulation

AIM: In the present study, an audio-visual sexual stimulation (AVSS) test was used to evaluate the effectiveness of sildenafil, and the AVSS test was coevaluated with the international index of erectile function (IIEF) questionnaire. METHODS: Forty-two patients with erectile dysfunction (ED) were examined (age range, 28-73 years; mean, 51.9 +/- 11.4 years). Each patient answered the IIEF questionnaire and underwent laboratory tests and the AVSS test before administration of sildenafil. The IIEF questionnaire and AVSS test (1 h after administration of 25 mg or 50 mg sildenafil) were re-evaluated in the outpatient clinic 4 weeks later. Questions 3 and 4 of the IIEF test were used to evaluate the effectiveness of sildenafil. Sildenafil was determined to be effective if each score totalled four or five after administration. RESULTS: The rate of effectiveness of sildenafil was 52.4%, and the mean score of the IIEF 5 improved from 7.2 to 15.4 following treatment with sildenafil. The maximum and mean rigidity of the penile tip improved after the sildenafil treatment (36.1%vs 57.7% and 14.2%vs 35.8%, respectively). The maximum and mean rigidity of the penile base rose (42.4%vs 57.7% and 17.9%vs 36.8, respectively). Similarly, following treatment with sildenafil, the penile tumescence increased from 6.6 cm to 7.6 cm at the penile tip and from 7.5 cm to 8.5 cm at the penile base. CONCLUSIONS: In some ED patients the results of the IIEF questionnaire are not always consistent with those of objective evaluation, including AVSS. In these patients, combined assessment using the IIEF and AVSS might be more useful to evaluate the precise effectiveness of sildenafil, rather than relying on the IIEF results alone.     

Combination therapy for erectile dysfunction: a randomized, double blind, unblinded active-controlled, cross-over study of the pharmacodynamics and safety of combined oral formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in men with moderate to severe erectile dysfunction

Oral therapy has become first line treatment for patients with mild to moderate erectile dysfunction (ED). Studies have shown that sildenafil may not be effective in all patients, and has been associated with a variety of adverse effects and an adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes. The objective was to compare the efficacy and safety of three different oral combinations with the highest dose of sildenafil in men with moderate to severe ED. Randomized, double blind, unblinded active-controlled, Phase II study was carried out at three sites in Mexico. After a 4-week placebo run-in period, patients received all four of the following treatments using a 4-way cross-over design: 40 mg phentolamine (PM) +6 mg apomorphine (Apo); 40 mg PM +150 mg papaverine (Pap); 40 mg PM +6 mg Apo +150 mg Pap (Tricombo); 100 mg sildenafil (SC). With the exception of sildenafil tablets, all study medication was blinded. Moderate to severe ED was defined as a less than 50% vaginal penetration success rate during the placebo run-in period. A total of 44 patients were enrolled, of whom 36 completed all four treatment periods. All treatments produced a significant effect in primary efficacy variable (Sexual Encounter Profile) compared to baseline, however, no statistically significant differences were found between treatments. A significant period effect was observed. Also, the four treatments were found not to differ significantly in five out of six secondary efficacy variables. The lowest incidence of treatment-related adverse events (AE) occurred in the 40 mg PM +6 mg Apo group (9.8%), followed by 100 mg SC (15%), and the other two combinations (16.7 and 17.5%, respectively). Nasocongestion and headache were the most frequently reported AE. An oral combination of vasoactive agents may provide an alternative approach to sildenafil. Based on these results a combination of phentolamine and apomorphine warrants further clinical investigation.     

Improved spontaneous erectile function in men with mild-tomoderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year： a randomized trial

Aim： To test the hypothesis that sildenafil （50 mg nightly for one year） can improve spontaneous erectile function （EF） in men with mild-to-moderate arteriogenic erectile dysfunction （ED） responsive to erectogenic treatment. Methods： In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function （IIEF EF） and the peak systolic velocity （PSV） of penile cavernous arteries were used to measure the efficacy. Results： After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 （60.4%, 95% confidence interval [CI]： 45.3-74.2%） of the nightly group vs. 4 of 49 （8.2%, 95% CI： 2.3-19.6%） of the as-needed group. PSV improved by 11.2 cm/s （95% CI： 4.7-21.4; P = 0.012） in the nightly group but only by 3.4 cm/s （-5.1- 14.7; P = 0.435） in the as-needed group. IIEF EF normalized in 1 of 18 （5.6%, 95% CI： 0.1-27.3%） non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most （28/29, 97%） nightly group men who had initially normalized. Conclusion： Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.     

Erectile dysfunction after kidney transplantation: our 22 years of experience

AIM: To evaluate the results of treatment of erectile dysfunction (ED) in kidney transplant recipients before and after the advent of sildenafil. MATERIALS AND METHODS: From 1981 through 2002, 971 male patients of mean age 53.4 years received a renal graft. Erectile dysfunction (ED) was investigated in all patients at the first urologic visit posttransplantation. Psycho-sexual support was offered to all patients. Before sildenafil use (1998), our diagnostic approach was complex. From 1998 we tested: serum levels of testosterone, prolactin, and glucose with penile duplex ultrasonography and NPT reserved for selected cases. RESULTS: From 1981 through 1998, 365 male kidney transplant recipients (45%) reported ED. Only 169 patients chose to be treated: 27 responded to psycho-sexual therapy; 3 received testosterone with benefit; 133 had a good results from intracavernosal injection of vasoactive drugs; and 6 received a penile prosthesis. Since 1998, 126 patients reported ED (78.3%). Only 78 chose treatment: 24 patients had a satisfactory response to sildenafil (65% with 50 mg and 35% with 100 mg). PGE1 alone or in combination with papaverine and phentolamine produced a good response in 37 patients; 17 patients did not respond to pharmacotherapy; and 5 received a tricomponent penile prosthesis without complications. The side effects of sildenafil and PGE1 therapy were similar to those reported in the literature. CONCLUSIONS: ED is an important problem in male renal transplant recipients. Cultural resistance to treatment is common. However, treatment with sildenafil citrate and intracavernosal self-injection of PGE1 are well accepted, and prosthetic devices may help in resistant cases.     

Impact of introduction of sildenafil on other treatment modalities for erectile dysfunction: a study of nationwide and local hospital sales

We assess the impact of introduction of sildenafil on alprostadil injection and penile implant surgery for the treatment of erectile dysfunction (ED) at our institution and in Taiwan. The data of national sales of sildenafil, alprostadil injection and penile implant were provided by industry companies. In the meanwhile, we analyzed the users of the above-mentioned three treatments at our institution. The national sales of sildenafil grew 136% from 0.8 million tablets in 1999 to 1.6 million tablets in 2002, while those of alprostadil injection dropped 33% after the marketing of sildenafil and of penile implant dropped 40% after the marketing of alprostadil injection and sildenafil. The market share of drugstores for sildenafil rose from 41% in 1999 to 72% in 2002. The trend of sales of sildenafil at our institution was similar to that of national sales from hospitals. Mean age of the sildenafil new users was becoming younger in the past 4 y (P<0.001). Of the new users of alprostadil injection and the recipients of penile implant, the commonest age group shifted from the range of 60-69 y before the launch of sildenafil to that of over 70 y after (P<0.05). In conclusion, the introduction of sildenafil has prompted more men as well as younger men with ED to seek treatment. Part of the roles of alprostadil injection and penile implants in this field are substituted by sildenafil and the commonest age group of their users becomes older than before.     

Efficacy, tolerability and satisfaction with sildenafil citrate 100-mg titration compared with continued 50-mg dose treatment in men with erectile dysfunction

OBJECTIVE

To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED).

PATIENTS AND METHODS

A multicentre, parallel‐group trial was conducted in two 4‐week periods. In period 1, patients received 50‐mg doses of sildenafil single‐blinded for 4 weeks. In period 2, patients were randomized to double‐blind, placebo‐controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged ≥18 years with a documented clinical diagnosis of ED (score of ≤25 on the International Index of Erectile Function, IIEF, Erectile Function, EF, domain), and met the prescribing criteria for sildenafil 50 mg and 100 mg.

RESULTS

Of 492 enrolled patients (mean age 53 years, sd 11), 476 (97%) completed period 1 and 473 (96%) completed period 2. Patients receiving sildenafil 50 mg in period 1 had an increase in the mean (sd ) baseline EF domain score from 12.8 (5.2) to 22.5 (6.6) (P < 0.001), and improved scores on the Quality of Erection Questionnaire (QEQ) and Sexual Experience Questionnaire (SEX‐Q). The IIEF EF domain scores were similar in the two groups at baseline and randomization. Patients titrated to the 100‐mg dose (237 men) showed a significantly greater improvement than those who continued on the 50‐mg dose (240; P < 0.001). There was a significant increase in QEQ and SEX‐Q scores in patients titrated to sildenafil 100 mg compared with patients continuing at sildenafil 50 mg. At either sildenafil dose, headache, flushing and hot flushes were the most common adverse events. Neither the frequency nor the severity of adverse events increased with titration to sildenafil 100 mg.

CONCLUSIONS

After initial treatment with sildenafil 50 mg, patients titrated to 100 mg showed further increases in efficacy and satisfaction with no increase in the number or severity of adverse events than in those remaining on the starting dose.     

西地那非和育亨宾治疗勃起功能障碍疗效比较

为了对照性研究应用西地那非（Ｓｉｌｄｅｎａｆｉｌ,Ｖｉａｇｒａ＾ＴＭ）和育亨宾治疗男子阴茎勃起功能障碍（ＥＤ）的疗效。把２３４例ＥＤ（器质性４１％,心理性４６％,混合性１３％）随机双盲分为两组,西地那非组１３４例,用西地那非５０～１００ｍｇ,性交前６０分钟口服,每天一次,连服２天后,改为２～３天服一次,连用４～１２周。育亨宾组１００例,用育亨宾（Ｙｏｈｉｍｂｉｎｅ）５．４～１０．８ｍｇ,每天服３次     

Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors.

The objective of this study was to determine the efficacy and safety of sildenafil in patients with erectile dysfunction (ED) and associated organic risk factors in a multispecialty clinic. Patients (n = 521) were diagnosed with ED based on self-assessment. Associated risk factors were managed by medication or life-style modifications, or both, before treatment with sildenafil for ED. Patients received a 50-mg dose of sildenafil that could be adjusted to 100 mg or 25 mg based on tolerability and efficacy. Patients recorded the number of successful intercourse encounters for 6 to 8 weeks, and the number of adverse events. Overall, there was an 82% successful intercourse rate with sildenafil treatment. The predominant associated risk factors for ED were hypertension (39%), hypogonadism (37%), and multiple medications (34%). Common adverse events due to sildenafil treatment were mild to moderate in nature and resulted in <2% patient discontinuation. Clinicians should be particularly careful to evaluate patients presenting with ED because the condition can be accompanied by a wide spectrum of risk factors requiring monitoring and treatment. However, with adequate treatment and control of these risk factors, the use of sildenafil in a representative population of men with ED in a multispecialty clinic can achieve a higher efficacy rate than previous studies have indicated.     

Daily use of sildenafil improves endothelial function in men with type 2 diabetes

Diminished vascular endothelial function results in decreased vasodilator capacity and is associated with erectile dysfunction (ED) in patients afflicted with type 2 diabetes. The current study was designed to evaluate whether daily use of sildenafil could alter endothelial function and improve penile rigidity in a group of patients with diabetic ED. A double-blind, placebo-controlled, prospective trial was conducted with 24 men with type 2 diabetes who were randomized into 2 groups: one receiving daily sildenafil (50 mg, n = 12) and the other placebo (n = 12) for 10 weeks. Erectile function was captured subjectively using the International Index of Erectile Function (IIEF-5), and endothelial function was objectively monitored via brachial artery flow-mediated dilation. Among the placebo and sildenafil groups, there were no significant differences in average patient age, time from type 2 diabetes diagnosis, duration of ED, or baseline IIEF-5 scores. Past medical histories, including smoking, alcohol consumption, hypertension, and hyperlipidemia, were also similar. At the conclusion of the 10-week trial, patients who received daily sildenafil had significantly improved erectile rigidity as captured by IIEF-5 (P < .001) and increased endothelial function via brachial artery flow-mediated dilation (P < .01). Endothelial function in men with type 2 diabetes was enhanced with daily sildenafil. Improved erectile rigidity and enhanced vascular circulation was noted after 10 weeks of daily sildenafil use.     

Clinical efficacy and safety of sildenafil in elderly patients with erectile dysfunction

Erectile dysfunction (ED) is a common medical disorder affecting elderly men. Sildenafil citrate has been shown to be an effective and well-tolerated oral agent for treating ED in the general population of adult men with ED of broad-spectrum etiology. Elderly men are more likely to have concomitant medical problems than the general population of men with ED. In this study, we examined the efficacy and safety of sildenafil administration in elderly patients with ED. Forty-four elderly men with ED (> or = 60 years old) of broad-spectrum etiology were treated with 25 mg or 50 mg doses of sildenafil citrate. Age ranged from 60 to 78 years (65 +/- 4.5; means +/- S.D.). Mean follow-up period was 12.3 +/- 6.5 months, with a range of 1 to 25 months. Primary efficacy assessments were performed using the International Index of Erectile Function 5 (IIEF5) before their first dose of sildenafil and after at least 4 weeks of therapy. Serum testosterone was measured before treatment. The mean IIEF5 among all patients increased from 8.5 +/- 3.9 to 20 +/- 4.2 after sildenafil use (P < 0.0001). In patients younger than 70 years, the IIEF5 score increased from 9.5 +/- 5.0 to 17 +/- 4.3 while in patients 70 years and older, the score increased from 8.2 +/- 3.6 to 21 +/- 3.9, a near normalization. The rate of improvement in younger men was higher than in older men. Serum testosterone before treatment was similar in the two groups. The most commonly experienced adverse events were flushing and dyspepsia, which occurred in 6.8% and 2.3%, respectively. No patients discontinued sildenafil treatment due to adverse events. In conclusion, oral sildenafil is efficacious and well tolerated by elderly men with ED, even among those older than 70 years.     

Potentiation of apomorphine effect on sildenafil-induced penile erection in conscious rabbits

Aim: To investigate a possible potentiation effect of apomorphine (APO) on sildenafil-induced penile erection in the conscious rabbit. Methods: Erection of male New Zealand White rabbits (3.5 - 4.0 kg, n=12) was assessed by measuring the length of the uncovered penile mucosa and the duration of erection before and after intravenous administration of agents. After injection of APO (0, 0.05, 0.1 and 0.4 mg/kg), sildenafil was administered intravenously in a dose-response manner (0.5, 1 and 5 mg/kg). In additional experiments, the effect of increasing doses of sildenafil in combination with APO on systemic blood pressure was evaluated. Results: Systemic administration of sildenafil induced a dose-dependent increase in the penile length. Intravenous injection of APO alone did not produce any change in the penile length, while significantly enhanced the penile erection induced by sildenafil. The co-administration of 0.1 mg/kg of APO and 1 mg/kg of sildenafil was found to be the most effective combination in producing penile erection. Intravenous administration of sildenafil caused a concentration-dependent decrease in systemic blood pressure, but no additional decrease was observed with co-administration of APO. Conclusion: APO enhances the penile erection induced by sildenafil in the conscious rabbit without causing an additional decrease in blood pressure. (Asian J Androl 2004 Sep; 6: 205-209)     

Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence

Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVE

To test the hypothesis that a variable dosage of the oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil (25, 50, 100 mg) or vardenafil (5, 10, 25 mg) determined according to results obtained from nocturnal penile tumescence and rigidity (NPTR, RigiScan), given nightly for 1 year, can improve spontaneous erectile function (EF) in men with mild‐to‐moderate arteriogenic erectile dysfunction (ED); this regimen was compared with a fixed daily dosage of sildenafil 25 mg or vardenafil 5 mg.

PATIENTS AND METHODS

In a prospective open‐label, parallel‐group trial 154 men with ED were randomized either to fixed low‐dose sildenafil 25 mg or vardenafil 5 mg (group 1) or to the lowest erectile dosage of sildenafil (25, 50 or 100 mg) or vardenafil (5, 10 or 20 mg) (group 2) provoking an erectile event as measured by NPTR nightly for 1 year. The EF domain of the International Index of Erectile Function (IIEF) was assessed before and 1 year after the beginning of treatment, and at 4 weeks after ending treatment.

RESULTS

After 1 year, 27 of 63 (64%) evaluable men in group 1 had an EF domain score in the normal range, vs 46 of 61 (75%) men in group 2. After the subsequent 4‐week wash‐out phase, both groups continued to have improved EF domain scores; 22 of 63 (35%) men in group 1 still had a score in the normal range, whereas 38 of 61 (62%) in group 2 had a normal score. The EF domain score in group 1 and 2 improved significantly after 1 year of treatment, from 13.6 to 18.9, and 15.1 to 23.9, respectively (P < 0.01). After the subsequent 4‐week wash‐out phase, men from both groups maintained this significant level of EF, at 17.1 and 22.4, respectively (P < 0.05).

CONCLUSION

Nightly PDE5‐inhibitor treatment 1 year in a dosage determined by NPTR measurements results in better EF than giving a fixed dosage of sildenafil (25 mg) or vardenafil (5 mg). This improvement persisted for >4 weeks beyond the end of treatment. The results from this open‐label, randomized trial warrant verification under double‐blind, placebo‐controlled conditions.     

Outcome analysis of sildenafil citrate for erectile dysfunction of Japanese patients

The approved maximal dose of sildenafil is only 50 mg in Japan, but the impact of dose regulation on treatment outcomes has not been established. Moreover, the contributors to the efficacy in patients having an intact peripheral nervous system have not been fully elucidated. We assessed in Japanese patients the treatment outcomes of sildenafil for erectile dysfunction (ED) under regulation of the approved dose and identified factors contributing to its efficacy among those with various etiologies other than pelvic surgery. We retrospectively reviewed 196 ED patients treated with sildenafil. The overall efficacy was 70.9% (139/196), and patients with psychological problems and concomitant cardiovascular disease showed high response rates (82.4 and 87.0%, respectively). Of the 139 responders, 89.9% achieved efficacy with a dose of 25 or 50 mg. Logistic regression analysis revealed concomitant cardiovascular disease and a favorable nocturnal penile tumescence result to be independent contributors to the efficacy.     

西地那非治疗勃起功能障碍无效的原因分析及治疗对策

目的 分析按需口服西地那非治疗勃起功能障碍(ED)无效原因并制定治疗策略.方法 2009年1-12月因ED就诊、正确服用西地那非100 mg、至少4次无效的患者126例.采用国际勃起功能指数调查表5个简化问题(IIEF-5)评分、实时勃起功能检测、血清睾酮检测、阴茎多普勒超声检查评估ED治疗无效的原因,患者进行充分的性教育,接受每晚西地那非50 mg治疗.采用IIEF-5评分和性生活日记问题2和3评价再次治疗后的效果.结果 126例ED患者中心理性ED41例,合并睾酮水平低下39例,糖尿病性ED 28例,血管性ED 18例.经过每日小剂量西地那非治疗4周,治疗前后IIEF-5评分分别为(12.3±2.9)分和(18.8±4.4)分,差异有统计学意义(P＜0.05).成功完成性生活者78例,有效率61.9%.结论按需口服西地那非治疗无效的患者经过充分的性教育、长期小剂量治疗后,大部分患者对西地那非治疗仍然有效.

Abstract：

Objective To assess the causes of sildenafil failure and the feasibility of successfully rechallenging non-responding patients. Methods A total of 126 consecutive erectile dysfunction (ED) patients from Jan 2009 to Dec 2009 who claimed poor response to sildenafil (sildenafil 100 mg on demand, at lease 4 epiodes) were enrolled into the study. All patients received sexual reeducation and were treated with sildenafil, taken on a daily dose of 50 mg for 4 weeks. The International Index of Erectile Function-5 (IIEF-5), Rigiscan, serum testosterone or penile Doppler were used to evaluate ED and the cause of on-demand sildenafil failure. End point efficacy of rechallenging was evaluated using the IIEF-5 and the sexual encounter profile (SEP) 'Were you able to insert your penis into your partner's vagina?' and 'Did your erection last long enough to achieve successful intercourse?'. Results The recruited patients comprised of 41 cases with psychological ED, 39 cases with hypogonadism ED, 28 cases with diabetes mellitus ED and 18 cases with vascular ED. Compared with pretreatment and on-demand sildenafil baseline, daily administration of sildenafil significantly enhanced all efficacy outcome variables. The IIEF-5 was significantly improved after daily sildenafil (12.3 ± 2.9 vs18. 8±4.4, P＜0.01), 78 patients responded to daily sildenafil. The overall salvage rate was 61.9%(78/126). Conclusions Sexual reeducation and daily administration of sildenafil may be able to salvage many patients with ED who were sildenafil non-responders.