Efficacy and safety of tadalafil for erectile dysfunction in patients with multiple sclerosis.

INTRODUCTION: Data are sparse concerning the effects of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) in subjects with multiple sclerosis (MS). AIM: To evaluate the efficacy and safety of tadalafil use in subjects with ED because of MS. METHODS: Ninety-six MS patients with ED after a 4-week treatment-free period were given tadalafil 10 mg. All patients were re-evaluated after 4 weeks. Those with a score lower than 26 on the International Index of Erectile Function (IIEF-15) and with less than 75% of total successful sexual attempts assessed by the Sexual Encounter Profile Questions 2 and 3 (SEP2-3) had their dosage of tadalafil increased to 20 mg, whereas responding subjects continued with 10 mg. Subsequently, all patients had a final follow-up visit after 8 weeks. MAIN OUTCOME MEASURES: SEP2-3, IIEF-15 questionnaire. The Life Satisfaction Checklist (LSC) questionnaire composed of eight questions was used prior to starting tadalafil and at the end of the 12-week treatment. RESULTS: Ninety-two subjects completed the study. Seventy-two responded, 30 of whom used 10 mg. Two subjects discontinued the therapy because of moderate side effects: one suffered from headache and one from tachycardia. Responding patients reached a significant statistical improvement in all follow-ups compared with baseline on the erectile domain and overall sexual satisfaction scores of the IIEF-15 using the Wilcoxon test P < 0.01. Furthermore, they showed statistical improvement through the Wilcoxon test P < 0.01 on the sexual life, family life, and partner relationship questions of the LSC compared with baseline. CONCLUSION: Tadalafil is an effective and safe treatment for males with MS suffering from ED. Further studies are needed on MS patients to evaluate the efficacy and safety of long-term use, and to detect predictable parameters for the success of PDE5 inhibitors.

Ten-year follow-up of sildenafil use in spinal cord-injured patients with erectile dysfunction.

INTRODUCTION: Data are sparse concerning the long-term effects of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED). AIM: To evaluate the efficacy and safety of long-term sildenafil use in subjects with ED caused by spinal cord injury (SCI). METHODS: Phase 1: From October 1998 to January 1999, 113 SCI patients with ED were given 50 mg of sildenafil after a 4-week treatment-free period. Those with a score lower than 26 on the International Index of Erectile Function (IIEF-15) and with less than 75% total successful sexual attempts the dosage of sildenafil was increased to 100 mg. Attempts were evaluated using the Sexual Encounter Profile Questions 2 and 3 (SEP2 and 3) regarding respectively the capacity to penetrate their partner and to maintain the erection after penetration. Phase 2: Only responding patients entered phase 2 where they were evaluated every 6 months. The final visit was concluded by January 2009. MAIN OUTCOME MEASURES: Follow-up using the IIEF-15 questionnaire every 6 months. RESULTS: Seventy-five patients entered Phase 2. Thirty-eight patients were excluded, 35 of them because they did not respond to the drug. Lesions higher than T12, an incompleteness of lesions, and higher residual erection were significant predictable factors for the success of the therapy (P < 0.05). Phase 2: the most frequent reason (68.3%) for discontinuing treatment was the desire to try a new oral therapy especially for patients using 100 mg. Thirty-four individuals continued treatment, 28 of whom took 50 mg. CONCLUSION: Sildenafil represents an effective and safe long-term option for SCI subjects with ED. Further investigation of long-term use of oral PDE5 inhibitors in SCI patients is needed for evaluating both factors that are determinant in the choice of a starter treatment and in detecting elements that influence the switching from initial treatment.

Ten years of phosphodiesterase type 5 inhibitors in spinal cord injured patients.

INTRODUCTION: The majority of men with spinal cord injury (SCI) require chronic treatment for erectile dysfunction (ED), but most of them, prior to taking phosphodiesterase type 5 (PDE5) inhibitors, stopped therapy due to side-effects or low compliance rate. AIM: Analysis of literature on oral PDE5 inhibitors in individuals with SCI and ED in order to evaluate how much their release changed the management of ED in SCI subjects and what remains to be seen of their potential or limits. MAIN OUTCOME MEASURES: Questionnaires on sexual function. METHODS: 18 internationally published clinical studies that enrolled SCI males treated with at least one of the PDE5 inhibitors were analyzed. RESULTS: The small numbers of papers with large and diverse outcome measures did not consent a meta-analysis of treatment results. 705 used sildenafil, 305 vardenafil and 224 tadalafil. Median age was less than 40 years. Only 1 study excluded tetraplegic individuals. For measures of ED evaluated, 11 out of 13 studies reported a significant statistical improvement with PDE5 inhibitors versus placebo or erectile baseline (P < 0.01, or p < 0.005). The most frequent predicable factor for the therapeutic success of PDE5 inhibitors was upper motoneuron lesion. Statistical impact on ejaculation success rates was shown in at least one paper for all PDE5 inhibitors (p < 0.05). Overall, 15 patients, (7 using sildenafil), discontinued the therapies due to drawbacks. Only 1 sildenafil study reported a follow-up maximum of 24 months. CONCLUSIONS: Literature suggests that all oral PDE5 inhibitors represent a safe and effective treatment option for ED caused by SCI. Further research is needed on head-to-head comparative trials and SCI patient preference for these drugs; their impact on ejaculation and orgasm function, their early use after SCI for increasing the recovery rate of a spontaneous erection, and their effectiveness and tolerability in the long-term are still to be investigated.

Efficacy and safety of medium and long-term tadalafil use in spinal cord patients with erectile dysfunction.

INTRODUCTION: The efficacy of phosphodiesterase type 5 inhibitors for a broad spectrum of erectile dysfunction (ED) is largely reported in literature. Data are lacking concerning medium and long-term effects and safety of these treatments. AIM: The aim of this study was to evaluate the efficacy and safety of medium and long-term use of tadalafil in subjects with ED because of spinal cord injury (SCI). METHODS: Phase 1: From March 2003 to March 2007, 103 SCI patients with ED, mean age 39 years, were given 10 mg of tadalafil after a 4-week treatment-free period. For patients with a score lower than 26 in the erectile domain of the International Index of Erectile Function (IIEF15) and with total unsuccessful sexual attempts of more than 25% according to the Sexual Encounter Profile questions 2 and 3 (SEP2-3), the dosage of tadalafil was increased to 20 mg. Phase 2: Only responding patients entered phase 2 where the subjects were evaluated in office visits every 6 months using the IIEF15 questionnaire and a diary reporting the day and time the drug was taken. All final visits were concluded by May 2008. MAIN OUTCOME MEASURES: The improvement of ED was measured using the IIEF15 and the SEP2-3 questions. RESULTS: Twenty-nine patients were excluded from phase 2: Twenty-seven did not respond to the drug and two left the study because of mild drawbacks. During the 6-month follow-up, nine left the study. Sixty-five individuals continued treatment with median follow-up of 33.6 months, 31 of whom took 10 mg and 34 who used 20 mg. Each group maintained up until the final visit a significant statistical improvement in erectile function, sexual satisfaction, overall satisfaction and percentages of "yes" responses to the SEP2-3 compared with baseline using the Wilcoxon test (P < 0.05). CONCLUSION: Tadalafil represents an effective and safe long-term option for SCI patients with ED.

Sacral neuromodulation for lower urinary tract dysfunction and impact on erectile function.

INTRODUCTION: The first sacral nerve stimulators were for urinary urgency incontinence, urgency-frequency, and nonobstructive urinary retention. Since then, observations have been made for benefits beyond voiding disorders. AIM: To evaluate if sacral neuromodulation (SNM) using the InterStim system (Medtronic Inc., Minneapolis, MN, USA) improves erectile function. METHODS: From January 1999 to January 2007, 54 males, mean age 42.8, underwent a permanent SNM for lower urinary tract symptoms (LUTS). Pre-SNM only subjects with concomitant erectile impairment according to the five-item version of the International Index of Erectile Function (IIEF-5), with normal blood sexual hormonal status, and responding to an intracavernous injection test 10 microg were enrolled in our study. Three months after permanent implantation, the IIEF-5 was completed again. Those who benefited significantly in erectile function completed the IIEF-5 semiannually. A final checkup was performed in July 2007. MAIN OUTCOME MEASURES: A score of IIEF-5 equal to or higher than 25% compared to baseline indicated remarkable clinical enhancement. RESULTS: Presurgery, two patients were excluded. Overall, 22 subjects (42.3%) showed erectile impairment (14 were neurogenic). In the first visit post-SNM, five retentionists of neurogenic origin and two with overactive bladder syndrome of idiopathic origin achieved noticeable erectile improvement. Their median IIEF-5 score shifted from 14.6 to 22.2, and 15.5 to 22.5, respectively. During follow-up, two neurogenics lost the benefits concerning voiding and erection and recovered them after a new implant in the contralateral sacral S3 root. In the final visit, the seven responders reached an IIEF-5 score of at least 22. CONCLUSIONS: Our study showed a clinically important benefit of sexual function mainly for neurogenic retentionists. Future research should test SNM in a larger sample of subjects, exclusively with sexual dysfunctions, in order to better understand the mechanism of action of SNM on erectile function.

Clinical female sexual outcome after sacral neuromodulation implant for lower urinary tract symptom (LUTS).

INTRODUCTION: Over the last few years, sacral neuromodulation (SNM) has become an established treatment option for lower urinary tract symptoms (LUTS). AIM: To evaluate if SNM improves sexual function in females treated with SNM for LUTS. MAIN OUTCOME MEASURES: Improvement in sexuality by the Female Sexual Function Index (FSFI) and the Female Sexual Distress Score (FSDS). MATERIALS AND METHODS: We included 31 women, 17 of whom were neurogenic with permanent SNM. Prior to the neuromodulation screening, we assessed sexual function through blood sexual hormones, the FSFI and the FSDS questionnaires. Significant enhancement in sexuality meant an increase of 60% of the total score or of one FSFI domain, or 50% improvement on the FSDS. Only females who showed significant benefits in the first visit post-permanent SNM repeated the questionnaires in follow-up. All these women had their final visit by July 2007. RESULTS: Both questionnaires indicated a clinically significant improvement in sexuality that was maintained up to the final visit for 4 out of 11 neurogenics with sexual dysfunctions: one showed arousal and desire disorders, one showed arousal disorder and lubrication impairment, one showed arousal disorder and pain, and one showed desire and orgasm deficits. Mean duration of sexual improvement was 23 months. Notable clinical improvement in sexuality was observed in two out of eight idiopathics (one suffering from arousal and desire disorders, and one from lubrication impairment) with a median follow-up of 22 months. CONCLUSIONS: The positive effects regarding sexuality may be due either to enhancement of LUTS or to the direct stimulation of the sacral roots (S3).

Neurogenic detrusor overactivity treated with english botulinum toxin a: 8-year experience of one single centre.

OBJECTIVE: Determine long-term effect of English botulinum neurotoxin type A (BoNTA; Dysport) for refractory neurogenic detrusor overactivity (NDO) for possible reduction of BoNTA efficacy after repeated injections. METHODS: Between 1999 and 2005, 199 patients with spinal cord lesions with refractory NDO were treated with Dysport. All patients underwent a clinical examination, urinalysis, and videourodynamic study at baseline and at 3, 6, and 12 mo after each treatment, as well as a visual analogue scale (VAS) assessment and a bladder diary checked for 1 wk before each visit. We used 1000, 750, 500 IU BoNTA at the beginning of our experience, and thereafter we mainly used 750 IU. Outcome measures included frequency of urge urinary incontinence (Incontinence Episode Frequency [IEF] test); urodynamic parameters including maximum cystometric bladder capacity (MCBC), reflex volume (RV), bladder compliance (BC); number of pads/condoms; antimuscarinic drug consumption; short- and long-term side-effects; and quality of life measured with VAS. RESULTS: No statistically significant differences were found in efficacy duration with the three Dysport doses (p=0.5274). The difference between the intervals of injections was not statistically significant (p=0.2659). MCBC, RV, and BC improved significantly after treatment compared with baseline values (p<0.001) and there were no statistically significant differences after each retreatment or regarding Dysport dose (p>0.05). There was a significant improvement in patient satisfaction after each retreatment as expressed on the VAS (p<0.001). There was a significant reduction in IEF score and pads/condoms use in the first 4 wk after each treatment (p<0.0001). CONCLUSION: After repeated injections the effect of BoNTA remained constant.

Vardenafil improves urodynamic parameters in men with spinal cord injury: results from a single dose, pilot study.

PURPOSE: We assessed urodynamic changes after vardenafil administration in spinal cord injured male patients on oxybutynin treatment. MATERIALS AND METHODS: We performed a single center, randomized, double-blind, placebo controlled trial in 25 patients with spinal cord injury who had erectile dysfunction and micturition disorders. A baseline urodynamic test was performed as well as a second urodynamic test 1 to 3 hours after the administration of 20 mg vardenafil and placebo in 15 and 10 cases, respectively. In all patients standard oral oxybutynin administration was not discontinued. Statistical assessment included the 3 urodynamic parameters maximum detrusor pressure during voiding, maximum cystometric capacity and detrusor overactivity volume. RESULTS: Placebo administration did not affect urodynamic parameters. After vardenafil administration maximum detrusor pressure was significantly decreased (59.3 vs 52.1 cm H(2)O, p <0.001) and maximum cystometric capacity considerably improved (233.5 vs 272 ml, p <0.001). The most dramatic variations were observed for detrusor overactivity volume (174 vs 218 ml, p <0.0001). In 7 patients with American Spinal Injury Association classification A and spinal cord injury above T6 we observed the most significant improvement in the evaluated urodynamic items, including maximum detrusor pressure 57 vs 52 cm H(2)O (p = 0.039), maximum cystometric capacity 253 vs 296 ml (p = 0.004) and detrusor overactivity volume 177 vs 229 ml (p = 0.003). CONCLUSIONS: This trial demonstrates that in spinal cord injured patients a single 20 mg vardenafil administration achieved a significant decrease in maximum detrusor pressure, an improvement in maximum cystometric capacity and a remarkable increase in detrusor overactivity volume value.

Female sexual dysfunction and hormonal status in spinal cord injured (SCI) patients.

To investigate a possible correlation between sexual hormonal status and the presence of female sexual dysfunction (FSD) using the Female Sexual Function Index (FSFI) in females with spinal cord injuries (SCI), we selected 39 SCI fertile-aged women. At visit 1, we assessed the presence of FSD using the FSFI, and all individuals were submitted to a blood hormone evaluation on the third day of their menstrual cycle. The levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid-stimulating hormone (TSH), cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstenedione, 17[alpha]-hydroxyprogesterone; total and free testosterone, 17beta-estradiol, inhibin, sex hormone-binding globulin (SHBG), and thyroid hormones (fT3 and fT4) were checked. Progesterone was measured on the 20th to 21st day after the menstrual cycle. In patients with amenorrhea, we tested all the hormones using 1 random blood test. After a 3-month period, the tests were repeated. Overall, 23/39 (58.9%) patients continued to manifest at least one sexual dysfunction. These patients reached a median score of 19.52. All but 6 patients (15.3%) consistently showed hormonal values within the normal range. Of the 6 patients with abnormal hormonal alterations, 5 showed at least one sexual dysfunction, 2 had low levels of total testosterone, 1 had a low level of free testosterone, 1 suffered from hypothyroidism, 1 presented with low levels of cortisol, and 1 showed hypoprogesterone. There was no significant correlation between abnormal hormonal status and the presence of a specific sexual dysfunction, as assessed with the FSFI.

Role of bladder neck preservation in urinary continence following radical retropubic prostatectomy.

OBJECTIVE: To report our experience of the influence of bladder neck preservation on patient continence. MATERIAL AND METHODS: Radical retropubic prostatectomy with bladder neck preservation was performed in 131 patients (age range 48-73 years; mean 64.5 years). Urinary continence was evaluated using a validated questionnaire at follow-up visits and telephone interviews. All patients reporting incontinence were studied using a pad test and urodynamics. RESULTS: After a mean follow-up period of 21.7 months (range 4-47 months), 115 patients were continent (87%) and 16 incontinent. According to the International Continence Society criteria, three had severe, three moderate and 10 mild incontinence. Urodynamics revealed sphincter deficiency in 15 cases, which was associated with decreased bladder compliance in four, while decreased compliance was the only abnormality in one. Continence was recovered 0-27 months after surgery (mean 3.2 months): 40% of men were continent within the first month and 74% within the third. Histopathology revealed positive margins in 30/131 patients (22%), but exclusively at the bladder neck level in only seven (5%), and two also had positive nodes. Six patients (4.5%) presented bladder neck stenosis requiring transurethral incision. No statistically significant differences were found between the ages of continent and incontinent men or between the time to continence recovery with two different techniques of retropubic hemostasis; however, use of a nerve-sparing technique significantly reduced the time to continence recovery. CONCLUSIONS: Bladder neck preservation during radical retropubic prostatectomy does not improve the long-term results of urinary continence but does contribute substantially to its earlier recovery, thus improving the quality of life. With proper patient selection the risk of positive margins at the bladder neck level only is reasonably low.