Sildenafil improves sleep-related erections in hypogonadal men: evidence from a randomized, placebo-controlled, crossover study of a synergic role for both testosterone and sildenafil on penile erections

To study the effects of sildenafil on human sleep-related erections according to the state of androgenization, we evaluated the effects of sildenafil on sleep-related erections in hypogonadal men before and during testosterone replacement treatment and in control subjects. We enrolled 24 hypogonadal men and 24 healthy men as a control group. All hypogonadal subjects had very low testosterone levels (<200 ng/dL [6.9 nmol/L]) [corrected] All subjects underwent nocturnal penile tumescence and rigidity monitoring (NPTRM) for 3 consecutive nights and were randomly assigned to consume either 50 mg of sildenafil or placebo 1 hour before bedtime on the second or third night of nocturnal penile monitoring. The hypogonadal subjects were tested twice, first without replacement treatment (H-T) and then after at least 6 months of testosterone replacement therapy (H+T). The subjects of the control group (C) were tested once. The following parameters of sleep-related erections were analyzed: total number of valid erections, total duration of both rigidity greater than or equal 70% and increase in penile circumference greater than or equal 30 mm, maximum rigidity, and maximum increase in penile circumference. NPTRM parameters were reduced in hypogonadal men before testosterone treatment (H-T+P) when compared with control subjects taking placebo (C+P). NPTRM parameters after testosterone (H+T+P) and sildenafil (H-T+S) administration were similar to that of control subjects taking placebo (C+P). When the statistical analysis was restricted to the hypogonadal men before testosterone treatment, sildenafil alone significantly increased NPTRM parameters when compared with placebo (H-T+S vs H-T+P). Testosterone restored normal erections when administered to hypogonadal subjects (H+T+P vs H-T+P); in hypogonadal men, however, the combined treatment (sildenafil plus testosterone) resulted in the maximum positive effect on NPTRM parameters. When the increase from baseline was analyzed, the effects of testosterone plus sildenafil were greater than the sum of the effects of each drug used alone. In conclusion, sildenafil administered at bedtime improves sleep-related erections in hypogonadal men, suggesting that the nitric oxide pathway may be pharmacologically enrolled and enhanced despite low serum testosterone. Furthermore, these data strongly support the idea of a synergic effect on sleep-related erections of sildenafil and testosterone.     

Sildenafil in the treatment of sexual dysfunction in spinal cord-injured male patients

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of sildenafil in the treatment of erectile dysfunction (ED) in spinal cord-injury (SCI) patients. Moreover, we looked for neurological conditions permitting therapeutic success and for the ideal dose needed to achieve sufficient erections. METHODS: 41 SCI patients were prospectively examined. Sexual dysfunction was assessed by means of anamnesis, the International Index of Erectile Function (IIEF) questionnaire, and neurological examination. Psychogenic erection capacity was tested by audiovisual stimulation and reflexive erection using a vibrator device. Neurophysiological recordings and cystomanometry were performed in parallel to clinical examinations. Neurophysiological recordings included sympathetic skin responses (SSR), pudendus somatosensory evoked potentials (pSSEP), and bulbocavernous reflex (BCR). Urodynamics aimed at classifying the neurogenic bladder dysfunction (upper motoneuron lesion versus lower motoneuron lesion). Intracavernous injection tests with PGE1 were performed in all patients to exclude major organic disease. 50 mg sildenafil was first given 3 times. Thereafter, the doses were adapted according to patients' reports. RESULTS: Clinically, 28 subjects preserved either reflexive erections (24) or psychogenic erections (4), 11 had both types and only 2 presented with a complete loss of erection. 38 patients (93%) had a positive response to sildenafil and reached a penile rigidity sufficient to permit sexual intercourse. 3 patients dropped out because of non-response despite having increased the dosis up to 100 mg. 22 patients (58%) showed functional erections 1 h after 50 mg sildenafil, whereas 14 (37%) required higher doses of 75-100 mg. By comparing the IIEF questionnaire scores before and after therapy, there was a significant improvement in erectile function and intercourse satisfaction from 9.2+/-4.4 SD) and 4.5 (+/-2.5 SD) to 25.5 (+/-4.2 SD) and 10.5 (+/-2.1 SD) points, respectively (p<0.05). Nearly 10% (4/41) suffered from side effects such as headache or dizziness. Two of them stopped therapy because of the side effects. At least 36 patients (88%) continue treatment with sildenafil. Absence of both psychogenic (nonsomesthetic supraspinally elicited) and reflexive (somesthetic spinally elicited) erections, confirmed by urodynamical and electrophysiological findings (SSR perineum, BCR and pSSEP), seems to exclude a successful treatment. In contrast, SCI male patients with preserved function of at least one component of the erection phenomenon (psychogenic/reflexive) responded well to sildenafil and the dose required to achieve erections sufficient for sexual intercourse did not differ between the two groups. CONCLUSIONS: Sildenafil proves to be a valuable and safe therapeutic management in ED of SCI patients. Therefore, patient acceptance and satisfaction are high. The most common dose required to achieve a satisfying erection is 50 mg. The efficacy of sildenafil depends on sparing of either sacral (S2-S4) or thoracolumbar (T10-L2) spinal segments which, in this study, have been shown to be of relevance in mediating psychogenic erections in male SCI patients. Complete disturbance of any neurogenic impulses excludes successful treatment.     

Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies

OBJECTIVES: To determine the efficacy and safety of fixed-dose oral sildenafil in patients with erectile dysfunction (ED) of various etiologies. METHODS: In a 12-week, double-blind, randomized, placebo-controlled, fixed-dose study, 514 men (mean age 56 years) with ED were randomized to receive 25, 50, or 100 mg of sildenafil or placebo. The primary etiology of ED was determined to be organic in 32% of men, psychogenic in 25%, or mixed in 43%. Sildenafil or placebo was taken in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of the IIEF, a global efficacy question, event log data, and a partner questionnaire. RESULTS: Sildenafil significantly increased patients' ability to achieve and maintain erections (P <0.0001), with efficacy increasing with increasing dose. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction, and overall sexual satisfaction (P <0.0001). The proportion of subjects who felt that treatment with sildenafil improved their erections was significantly greater (67% to 86%) than that with placebo treatment (24%, P <0.0001). The proportion of successful attempts at sexual intercourse also increased significantly with sildenafil treatment (P <0.001). Partner responses corroborated patient reports. Sildenafil was well tolerated at the three doses studied. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for ED of various etiologies.     

ASSESS-3: a randomised, double-blind, flexible-dose clinical trial of the efficacy and safety of oral sildenafil in the treatment of men with erectile dysfunction in Taiwan

The efficacy and safety of sildenafil were evaluated in a randomised, double-blind, placebo-controlled, flexible-dose study in Taiwanese men aged 26 to 80 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months' duration. A total of 236 patients were randomised at six medical centres in Taiwan to receive either sildenafil (50 mg initially increased if necessary to 100 mg or decreased to 25 mg depending on efficacy and toleration) (n=119) or matching placebo (n=117) taken on an 'as needed' basis 1 h prior to anticipated sexual activity for a period of 12 weeks. At the end of 12 weeks, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the IIEF (International Index of Erectile Function) scale, (2) the percentage of successful intercourse attempts; and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P<0.0001). Treatment-related adverse events occurred in 43.7% of patients receiving sildenafil and 18.8% receiving placebo. The most common adverse events with sildenafil were flushing, dizziness and headache (25.2, 6.7 and 5.9% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in the population of Taiwanese men appears similar to that reported in other studies in western populations.     

A double-blind,randomised- placebo,controlled, parallel group,multicentre, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea

The efficacy and safety of sildenafil was evaluated in a randomiSed, double-blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months duration. A total of 133 patients were randomised at six centres in Korea to receive either sildenafil (50 mg initially, increased if necessary to l00 mg or decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual activity for a period of 8 weeks. At the end of this time, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the International Index of Erectile Function (IIEF) scale, (2) the percentage of successful intercourse attempts, and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P&<0.0001). Treatment-related adverse events occurred in 56.1% of patients receiving sildenafil and 20.9% receiving placebo. The most common adverse events with sildenafil were vasodilatation (flushing), headache and abnormalities in colour vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in this population of Korean men appears similar to that reported in other studies in western populations.     

Effects of sildenafil on nocturnal penile tumescence and rigidity in normal men: randomized,placebo-controlled,crossover study

We studied the effects of sildenafil on sleep-related erections in 44 adult healthy men not affected by erectile dysfunction (mean age +/- SD: 39.3 +/- 10.5 years). No subjects were administered any medication the first night, but all were randomly administered sildenafil 50 mg or placebo the second night and vice versa the third night. Sildenafil and placebo were administered 1 hour before bedtime. The following parameters of sleep-related erections, after taking sildenafil or placebo, were analyzed: total number of valid erections, total duration of rigidity more than or equal to 70% of a tightening force of 2.8 N applied by the recording device, total duration of increase in penile circumference more than or equal to 30 mm, maximum rigidity, mean of maximum rigidity, and maximum increase of tumescence. Apart from the maximum increase of tumescence, all the parameters analyzed were significantly higher after sildenafil than after placebo administration during the first 4 hours of monitoring in all subjects (n = 44) (study 1). All the parameters were significantly higher after sildenafil than after placebo administration during the whole 8 hours of monitoring in 25 of 44 subjects (study 2A) who slept at least 8 hours. Comparing both the first and the second 4 hours in the 25 of 44 subjects who slept at least 8 hours (study 2B), all the parameters were significantly higher after sildenafil than after placebo administration, apart from maximum rigidity and mean of maximum rigidity during the first 4 hours. Our data suggest that sildenafil, administered at bedtime, is efficacious in improving sleep-related erections in normal men, indirectly confirming that the nitric oxide pathway is crucial in the physiology of erections during sleep. The effect of sildenafil is prolonged up to 8-9 hours after its administration.     

Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time

Sildenafil is one of two oral drugs approved for first-line treatment of erectile dysfunction (ED). Anecdotally, some young healthy men who wish to enhance their sexual performance are requesting or abusing sildenafil. In this randomized double-blind, placebo-controlled clinical study, we investigated the effect of sildenafil in young men without ED. A total of 60 young healthy men age 20-40 y with no reported ED were enrolled for this single-dose home-use study. Subjects had used no medication in the 6 months prior to the study. All had been engaged in a stable relationship for at least 3 months. After completing the IIEF-5 questionnaire, patients were randomized in a double-blind fashion to receive either one 25 mg tablet of sildenafil (group 1) taken prior to intercourse, or an identical placebo tablet (group 2). All subjects completed a questionnaire relating to their erectile quality. There were no differences between the two groups in the reported improvement of erection quality, 12/30 sildenafil vs 10/30 placebo (Fisher's test, P=0.79). Sildenafil caused a significant reduction of the postejaculatory refractory time (12/30 vs 4/30) (chi(2) test, P=0.04). Sildenafil does not improve erections in young healthy men. Sildenafil should not be given to young healthy men to improve their erections and patients should be advised against recreational abuse of the drug. In this limited single-dose home study, sildenafil appears to reduce the postorgasmic refractory time. Although controlled studies are needed to evaluate the efficacy of erection-enhancing drugs in premature ejaculation, it is possible that sildenafil might be useful for this indication.     

Erectile response with vardenafil in sildenafil nonresponders: a multicentre, double-blind, 12-week, flexible-dose, placebo-controlled erectile dysfunction clinical trial

OBJECTIVE: To evaluate the efficacy of vardenafil in patients previously unresponsive to sildenafil. PATIENTS AND METHODS: A multicentre, double-blind, 12-week, flexible-dose, placebo-controlled trial was conducted, involving 463 men aged > or = 18 years with moderate-to-severe erectile dysfunction (ED) and who were unresponsive to sildenafil (by history). After a 4-week treatment-free run-in, patients received placebo or vardenafil 10 mg with the option to maintain current dose or to titrate by one dose level (5, 10 or 20 mg) based on efficacy and tolerability at 4 and 8 weeks. Outcome measures were the erectile function (EF) domain score of the International Index of Erectile Function, two Sexual Encounter Profile diary questions (vaginal penetration and maintenance of erection until successful completion of intercourse), and the Global Assessment Question (GAQ). RESULTS: There was significantly better EF with vardenafil than with placebo throughout the study. The least-square mean EF domain scores increased from 9.3 at baseline to 17.6 at the 'last' observation carried forward (LOCF) analysis with vardenafil (P < 0.001). Overall least-square mean per-patient success rates more than doubled for penetration (30.3% to 62.3%) and quadrupled for successful intercourse (10.5% to 46.1%) with vardenafil. Improved erections (positive response to the GAQ) were reported by 61.8% of patients receiving vardenafil and 14.7% of those receiving placebo at LOCF (P < 0.001). Normal EF (domain score > or = 26) was achieved by 30% of patients receiving vardenafil and 6% receiving placebo at LOCF (P < 0.001). Adverse events were infrequent and representative of the phosphodiesterase-5 inhibitor profile. CONCLUSION: Vardenafil is an effective and generally safe treatment for ED, even in men unresponsive to sildenafil (by history).     

A Placebo-Controlled,Multicenter, Randomized,Double-Blind,Flexible-Dose,Two-Way Crossover Study to Evaluate the Efficacy and Safety of Sildenafil in Men With Traumatic Spinal Cord Injury and Erectile Dysfunction

Background/objective: To show the efficacy, safety, and tolerability of sildenafil in men with erectile dysfunction (ED) associated with complete or incomplete spinal cord injury (SCI) and to assess its effects onquality of life (Qol) using the Life-Satisfaction Check List.

Methods: This was a placebo-controlled, multicenter, randomized, double-blind, flexible-dose, 2-way crossover study with a 2-week washout period between each phase. Patients with ED attributable to SCI(Sexual Health Inventory-Male score ≤21) received 50 to 100 mg sildenafil (n = 24) or placebo (n = 26).

Results: Compared with placebo, sildenafil produced higher levels of successful sexual stimulation,intercourse success, satisfaction with sexual life and sexual relationship, erectile function, overall sexual satisfaction, and an improved Erectile Dysfunction Inventory of Treatment Satisfaction score, with no clinically relevant effects onvital signs. Sildenafil seemed more effective in patients with incomplete SCI than in those with complete SCI, producing significant improvements, compared with placebo, in a number of measures only in patients with incomplete SCI. All patients who expressed a preference selected sildenafil over placebo, although the drug had no effect on patient Qol. Sildenafil was well tolerated, with a profile comparable to that of placebo.

Conclusions: Compared with placebo, treatment with oral sildenafil safelyand effectively improved erectile function in patients with ED attributable to SCI, especially in those with incomplete injury, and was theagent of choice in those who expressed a preference.     

Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy

Four weeks after bilateral nerve-sparing radical retropubic prostatectomy, men with normal erectile function before surgery were randomized to double-blind sildenafil (50 or 100 mg) or placebo nightly for 36 weeks, followed by an 8-week drug-free period before assessment of erectile function. Enrollment was prematurely ceased and only 76 men completed because, assuming a placebo response rate similar to the published literature (for example, 34% in meta-analysis), the 25% response at blinded interim review suggested a lack of treatment effect. On the contrary, spontaneous erectile function (a combined score of >or=8 for questions 3 and 4 of the International Index of Erectile Function and a positive response to 'Were erections good enough for satisfactory sexual activity?') occurred in only 4% of the placebo group (n=1 of 25) versus 27% (n=14 of 51, P=0.0156, Fisher's exact test) of the sildenafil group. Nightly sildenafil administration for 36 weeks after surgery markedly increased the return of normal spontaneous erections.     

Time/duration effectiveness of sildenafil versus tadalafil in the treatment of erectile dysfunction in male spinal cord-injured patients

STUDY DESIGN: A randomized, blinded, crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction (ED) in male spinal cord-injured (SCI) patients. OBJECTIVES: To compare the safety, time/duration effectiveness, and the impact on the quality of life (QoL) of tadalafil 10 mg versus sildenafil 50 mg. SETTING: Neurourology Section, Careggi Hospital, Florence, Italy. METHODS: During a screening (visit 1), a diary card was distributed, in which the subjects assessed, after each attempt at intercourse the quality of their erection, responding (Yes/No) to both Sexual Encounter Profile Questions 2 (SEP2) and 3 (SEP3). The subjects made at least four attempts at intercourse. At visit 2, 15 patients (group 1) were assigned sildenafil and 15 (group 2) started with tadalafil. Responses to baseline International Index of Erectile Function 5 items (IIEF-5), Questions 13-14 (IIEF 15 items) and SEP diary were recorded. Patients attempted intercourse on four separate occasions: within 4 h of taking the first tablet, within 12 h for the second tablet, 24 h for the third, and the fourth from 24 to 36 h. At visit 3, the investigators evaluated the effectiveness with the same measures used at baseline. After a wash-out period, at visit 4, Group 1 was given tadalafil, and Group 2 was given sildenafil. Patients were required to observe the same criteria in taking the four tablets as in visit 2. After 4 weeks (visit 5), we evaluated the patients as we did in visit 3. RESULTS: Overall, 28 patients completed the study. No subjects discontinued the drugs due to drawbacks.Tadalafil allowed a majority of men in this trial to achieve both normal sexual functioning up to 24 h postdosing compared to sildenafil (P<0.01) and improved overall sex life satisfaction as well as sexual relations with partner. CONCLUSION: Based on these data, tadalafil may have the potential to become an important treatment option for ED in SCI patients. SPONSORSHIP: This study was not sponsored.     

Erectile function and male reproduction in men with spinal cord injury: a review

Spinal cord injury (SCI) in men results in defects in erectile function, ejaculatory process and male reproductive potential. There are alterations in the capacity of men with SCI to achieve reflexogenic, psychogenic and nocturnal erections. The sexual function in different stages after SCI and the types of erections depend mainly on the completeness of the injury and the level of neurological damage. Furthermore, most of the SCI men demonstrate defects concerning the entrance of semen into the posterior urethra and the expulsion of the semen through the penile urethra and the urethral orifice. In addition, SCI men develop defects in the secretory function of the Leydig cells, Sertoli cells and the male accessory genital glands. The overall result is a decreased quality of the semen is recovered either with penile vibratory stimulation (PVS) or with electroejaculation. Nowadays the therapeutic andrological approach of SCI men focuses on achievement of erectile function, recovery of spermatozoa and assisted reproductive technology. The first line of therapy recommended for infertility in SCI men is collection of semen via PVS with concomitant evaluation of total motile sperm yields for assisted conception which may include intravaginal insemination, intrauterine insemination, or in vitro fertilisation/intracytoplasmic sperm injection. Patients failing PVS may be referred for electroejaculation or surgical sperm retrieval.     

A European multicentre study to evaluate the tolerability of apomorphine sublingual administered in a forced dose-escalation regimen in patients with erectile dysfunction

OBJECTIVE: To determine the risk-benefit ratio of a forced dose-escalation regimen (2 to 3 to 4 mg) in a European clinical study evaluating apomorphine sublingual (SL) in treating erectile dysfunction (ED), by evaluating the overall tolerability and efficacy of the regimen compared with placebo in patients with ED, and evaluating efficacy by assessing the proportion of successful attempts resulting in sexual intercourse. PATIENTS AND METHODS: This randomized, double-blind, two-arm, parallel-group study was conducted in 507 patients enrolled at 34 European sites. After a 1-2 week screening period, patients were treated for 8 weeks with either placebo or apomorphine SL administered as a forced dose-escalation regimen. Heterosexual men (aged 18-70 years) were eligible for participation in the study if they were in stable health, a stable relationship of > or = 6 months duration, had a history of erectile inability, and were diagnosed with ED (successful in fewer than half of attempts to attain and maintain an erection firm enough for intercourse during the 30 days before screening). Patients provided information (recorded on diary cards and reviewed at each study visit) about the frequency and success in achieving erections and of sexual intercourse attempts during both the screening and treatment periods. The dosing regimen required patients to take one tablet of apomorphine SL (2 mg for 2 weeks, then 3 mg for 2 weeks and finally 4 mg for the remaining 4 weeks) or placebo 15-25 min before intercourse, and intercourse was to be attempted at least twice a week. Safety data were collected throughout the 8-week study period, and included recording adverse events, vital signs and changes in laboratory test values for standard haematology and biochemistry variables. The primary efficacy variable was the proportion of successful attempts, defined as an erection rigid enough for sexual intercourse, occurring after dosing (successful intercourse rate). The proportion of erections achieved was a secondary efficacy variable. RESULTS: Of the 507 patients, 254 received apomorphine SL and 253 received placebo; 87% of patients in both groups completed the 8-week treatment period. Of the patients receiving apomorphine SL, 24% had hypertension, 11% had coronary artery disease, 10% had diabetes, and 5.5% had benign prostatic hypertrophy; 62.6% of treated patients received concomitant medications for these maladies. The treatment groups were balanced for demographic and baseline variables, including comorbidity factors. Treatment-emergent adverse events, reported by > 5% of patients in the treated group, were nausea (9.8%), dizziness (7.1%) and headache (6.7%), compared with 0.4%, 2.4% and 4.0%, respectively, in the placebo group. Sixty-six patients withdrew from the study, 16 because of study drug-related adverse events (12 from the apomorphine and four from the placebo group). Six patients (three in each group) reported a total of nine serious treatment-emergent adverse events, all of which resolved by the end of the study. In the intention-to-treat population, the proportion of successful attempts at sexual intercourse and of erections were statistically greater in the apomorphine than in the placebo group (P = 0.001 and 0.021, respectively); analysis of the per-protocol population results confirmed this significant difference. CONCLUSION: This European study supports the safety and tolerability of apomorphine SL despite the forced escalation to a 4-mg dose (exceeding the approved 2-3 mg dose). Adverse effects were not treatment-limiting. These results further support the clinically significant efficacy of apomorphine SL for treating ED at all doses used. The risk/benefit ratio supports apomorphine SL as a safe and effective alternative in managing ED.     

Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries

OBJECTIUES: We investigated which nerve pathways are necessary to achieve ejaculation using penile vibratory stimulation (PVS) in men with spinal cord injury (SCI). METHODS: Eight men with SCI were selected based on the presence of a bulbocavernosus reflex (BCR) and consistent antegrade ejaculation with PVS. Level of injury was cervical (4), upper thoracic (4), and lower thoracic (1). Mean age was 30.4 years (range 22 to 38). Usual responses to PVS included autonomic dysreflexia (4), erection (4), and consistent somatic responses such as abdominal contractions (8). Local anesthesia of the dorsal penile nerves (penile block) was achieved using 1% plain lidocaine injection. Effective penile block was confirmed by loss of the BCR. Two PVS ejaculation trials were performed: one trial during the penile block and one trial when the penile block had worn off. In 4 subjects, the bladder contents were analyzed for retrograde ejaculation. RESULTS: With the penile block, ejaculation was inhibited in 100% of the subjects. None of the bladder washings demonstrated sperm, indicating absence of retrograde ejaculation. None of the subjects exhibited their usual erectile response, somatic responses, or signs of autonomic dysreflexia. After the penile block wore off, PVS induced ejaculation in all subjects. If subjects usually had erection, somatic responses, or signs of autonomic dysreflexia, these also returned. CONCLUSIONS: Our data suggest that ejaculatory response to PVS in SCI men requires the presence of intact dorsal penile nerves.     

Acupuncture in the treatment of psychogenic erectile dysfunction: first results of a prospective randomized placebo-controlled study

In a prospective study, we investigated the potentially curative effect of acupuncture in patients with psychogenic erectile dysfunction (pED). A total of 22 patients with pED were randomized into two groups. They were either treated with acupuncture specific against ED (treatment group) or acupuncture specific against headache (placebo group). Nonresponders of the placebo group were crossed over to the treatment group. Prior to acupuncture, serum sexual hormone levels, IIEF score, nocturnal penile tumescence testing for three nights (Rigiscan) and the erectile response to 50 mg sildenafil were evaluated. Out of 21 patients, 20 completed the study, including 10 patients after crossover. A satisfactory response was achieved in 68.4% of the treatment group and in 9% of the placebo group (P=0.0017). Another 21.05% of the patients had improved erections, that is, sufficient rigidity under simultaneous treatment with 50 gm sildenafil. The results of our pilot study indicate that acupuncture can be an effective treatment option in more than two-thirds of patients with psychogenic erectile dysfunction.     

Restorative increases in serum testosterone levels are significantly correlated to improvements in sexual functioning

It is recognized that testosterone (T) levels decrease in men with age, as does sexual function. We hypothesize that T supplementation in hypogonadal men with sexual dysfunction will restore certain elements of sexual function. Hypogonadal male subjects (total T < or = 300 ng/dL, n = 406, mean age 58 years) reporting one or more symptoms of low testosterone were randomized to T gel (50 mg/d and 100 mg/d), T patch, or placebo. Twenty-four-hour pharmacokinetic profiles for T were obtained. The 3 primary end points evaluated at 30 and 90 days posttreatment included a significant change in the frequency of intercourse and nighttime erections per 7-day week as well as a change in sexual desire measured on a Likert-type scale and calculated as a mean daily score. At day 30, a significant increase from baseline in sexual desire was noted for those on 100 mg/d T gel compared with those on 50 mg/d T gel, T patch, or placebo (1.2 vs 0.4, 0.7, and 0.4, respectively). A significant increase from baseline in the frequency of nighttime erections was also noted for those on 100 mg/d T gel compared with those on 50 mg/d T gel or placebo (51% of subjects in the 100 mg/d T gel group had an increase in frequency vs 30% for the 50 mg/d T gel group and 26% in the placebo group). Finally, a significant increase from baseline in the frequency of intercourse was evidenced for those on 100 mg/d T gel compared with those on T patch or placebo (39% of subjects in the 100 mg/d T gel group had an increase in frequency vs 21% for the T patch group and 24% in the placebo group). Similar results were seen for 100 mg/d T gel at day 90 for sexual desire and nighttime erections vs placebo. These data demonstrate a clear relationship between restoring serum T concentrations and improvement in certain parameters of sexual function. We propose that threshold T levels are needed in order to significantly affect improvements in sexual functioning.     

Efficacy of sildenafil citrate at 12 hours after dosing: re-exploring the therapeutic window

OBJECTIVE: This open-label study investigated the efficacy of sildenafil citrate at 12 hours postdose among prior treatment responders. PATIENTS AND METHODS: Eight 100-mg doses of sildenafil were provided to 40 eligible patients with erectile dysfunction (ED), who were to record the results of each sexual attempt in a patient diary. Each patient was instructed to make a sexual attempt at 1 and 12 hours postdose on 4 occasions (part 1) and only at 12 hours postdose on 4 subsequent occasions (part 2). RESULTS: Of 40 enrolled patients, 34 (85%) completed the study. In these evaluable patients, 97% and 74% of patients achieved erections that resulted in successful intercourse at 1 hour and 12 hours postdose, respectively. There was a nonsignificant reduction in the percentage of responders at 12 hours during part 1 versus part 2 of this study (71% versus 78%). CONCLUSIONS: This study demonstrates that, in the majority of these patients with ED, sildenafil remains clinically active 12 hours after administration. Larger studies may be necessary to confirm and clarify the therapeutic window of sildenafil.     

Efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction. A comparative crossover study

To compare the efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction (ED), 40 men were studied. Post-injection penile peak systolic velocity was greater than 25 cm s(-1). Twenty men started on apomorphine 2 mg and 20 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg, respectively, if necessary. After a 1-week washout period each group switched to the other treatment mode. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on an event log data. The majority (85%) of the men had concomitant diseases, risk factors for ED and 95% were heavy smokers. The overall success rate of apomorphine was 62.7%, compared with 73.1% of sildenafil (Yates-corrected chi-square, P < 0.0004). The response to apomorphine 2 mg and sildenafil 50 mg was age related. Sildenafil was statistically more effective than apomorphine in impotent men with normal penile Doppler. Given the contraindication of sildenafil in men taking nitrates and the quick time of action of apomorphine, the two drugs are satisfactory first line therapeutic tools in such individuals and the choice should be based on patient's needs and preferences.     

Comparison of the efficacy and safety of sildenafil citrate (Viagra) and oral phentolamine for the treatment of erectile dysfunction

This open-label, multi-center study from Mexico compared the efficacy and safety of oral sildenafil and phentolamine in men with erectile dysfunction. Patients received sildenafil (25-100 mg; n=123) or phentolamine (40 mg; n=119) for 8 weeks, and efficacy was assessed using the International Index of Erectile Function (IIEF) as well as two global efficacy questions. Mean scores for the erectile function domain of the IIEF were significantly higher for sildenafil (27.23 +/- 0.62; P=0.0001) than for phentolamine (19.35 +/- 0.66). Approximately twice as many men receiving sildenafil had successful attempts at sexual intercourse (88% vs 42%), improved erections (95% vs 51.1%), and improved ability to have sexual intercourse (94.4% vs 46.4%) compared with phentolamine. The most common adverse events included rhinitis, headache, tachycardia, and nausea, with a higher frequency reported in patients receiving phentolamine than sildenafil (41% vs 33%), with the exception of headache, which was reported more frequently in sildenafil users. Overall, sildenafil was more effective and appeared to be better tolerated than phentolamine for the treatment of erectile dysfunction.     

Long-term efficacy and safety of oral Viagra (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal

The long-term efficacy and safety of oral Viagra (sildenafil citrate), a selective phosphodiesterase 5 inhibitor, and the effect of withdrawing treatment were evaluated in men with erectile dysfunction (ED). In 233 men with ED of psychogenic or mixed organic/psychogenic aetiology, 16 weeks of open-label, flexible-dose sildenafil treatment (10-100 mg) was followed by eight weeks of double-blind, fixed-dose, randomised withdrawal to placebo or continued treatment with sildenafil. Sildenafil was taken as needed (not more than once daily) approximately 1 h prior to sexual activity. The main outcome measures were a global efficacy question, a sexual function questionnaire, an event log of erections, and adverse event recording. In the open-label phase, 200 of 216 patients (93%) reported improved erections with sildenafil; 28 patients (12%) discontinued treatment. In the double-blind phase, the significant improvements in the frequency and duration of erections were maintained in the sildenafil group but returned to pre-treatment values in patients on placebo (P values < 0.0001 versus placebo). The most frequent adverse events in the sildenafil group during the double-blind phase were flushing (7%), headache (6%), and dyspepsia (5%). Of the 192 patients enrolled in the 1-y extension, 90% completed the study; only two patients (1%) were withdrawn due to lack of efficacy. In men with ED of psychogenic or mixed aetiology, oral sildenafil is effective and well-tolerated both at the initiation of therapy and during long-term treatment. For most patients, sildenafil treatment must be continued for improvements in erectile function to be maintained.