Giuseppe Lombardi

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.

Clinical outcome of sacral neuromodulation in incomplete spinal cord injured patients suffering from neurogenic lower urinary tract symptoms

Objective:To determine the efficacy and safety of sacral neuromodulation (SNM) in incomplete spinal cord injured (SCI) subjects affected by neurogenic lower urinary tract symptoms (NLUTS).Methods:Twenty-four SCI patients were enrolled. The individuals were divided into two groups: 13 individuals in the urinary retention category and 11 suffering from overactive bladder syndrome. All subjects underwent definitive SNM implantation (Medtronic, Inc.). Voiding symptoms were assessed using patient bladder diaries, which recorded both pre-SNM and before each follow-up (1, 3 and 6 months, and then every 6 months). Outcome measures were per 24 h: number of voids and voided volume per void for both groups; number of urinary leakages, pad use and nocturia for patients with overactive bladder syndrome; and volume per catheterization and number of catheterizations for urinary retention subjects only. Final checkups were completed by June 2008.Results:Median follow-up was 61 months. Up to the final visit, all subjects maintained a clinical improvement of more than 50% compared with baseline. Twenty-two side effects were recorded. Four subjects with urinary retention needed a new implant in the controlateral S3 sacral root because of loss of efficacy. One patient with urinary retention developed a wound infection at the implanted pulse generator site.Conclusions:Our study contains the largest series of implanted SCI patients ever published. SNM is a therapy to consider in the treatment of NLUTS for partial SCI patients, even if the loss of clinical benefits for patients with retentive NLUTS must be taken into account. All adverse events were treated effectively.

Sexual dysfunction in women during dialysis and after renal transplantation.

INTRODUCTION Disorders of the reproductive system and menstrual abnormalities often associated with loss of libido and inability to reach orgasm are common in adults of both sexes with an end-stage renal disease. These symptoms may significantly contribute to depression and reduce the sexual activity of women. AIM To determine if sexual function, as well as hormonal status, improves after kidney transplantation, comparing a group of pre-menopausal women during dialysis and after a successful renal transplantation. METHODS We enrolled 58 women that received kidney transplantation. Patients included were 18-45 years old, on hemodialysis for more than 6 months following a fully functioning kidney transplantation, and on a stable corticosteroids immunosuppressive regimen for at least 6 months. All women underwent a general and urogynecological examination, a hormonal profile determination, and filled out the Female Sexual Function Index (FSFI) and a Beck Depression Inventory questionnaire administered during dialysis and 12 months after transplantation. MAIN OUTCOME MEASURES We evaluated the prevalence of Female Sexual Dysfunction according to the FSFI cutoff points, sexual hormonal status, and menstrual status during dialysis and 12 months after kidney transplantation. RESULTS Nineteen out of 58 women left the study prematurely. Thirty-nine women (mean age 36 +/- 5.9 years) completed the study. A total of 74% of the patients had menstrual disturbances during dialysis, as opposed to 45% after transplantation (P < 0.001). Sixteen out of 39 (41%) patients acknowledged having an active sexual life during dialysis. Thirty-four out of 39 (88%) transplanted patients acknowledged having an active sexual life (Fischers exact test P = 0.000039). The hormonal profile and FSFI results improved significantly after transplantation. CONCLUSION This study demonstrates that a successful transplantation should improve the sexual life in women with chronic renal failure.

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).

Sexual rehabilitation in women with spinal cord injury: a critical review of the literature

Study design:Review article.Objectives:Critical review of literature on the multiple aspects of sexual rehabilitation in women with spinal cord injury (SCI) from initial recovery to long-term follow-up.Setting:Neuro-urology Department.Methods:Studies on sexuality selected from PubMed from 1993 to 2009.Results:Literature supported by significant statistical analyses reports that females with complete tetraglegia deserved special attention immediately at initial recovery; sexual intercourse is much more difficult for them (as compared with other women with SCI) mainly because of autonomic dysreflexia and urinary incontinence. There are sparse data on predictable factors favoring sexual rehabilitation such as the age SCI was incurred, the importance of ones sexual orientation, and the SCI etiology. Information after initial discharge is based chiefly on questionnaires, which report that as more time passes since the injury, patients attain more sexual satisfaction compared with recently injured women. Studies on neurological changes after SCI, and their effect on sexual response, are supported by a significant statistical analysis, but with few SCI patients. One topic reported the effect of sildenafil on sexuality, without benefit. No paper offers any detailed analysis on the sexual impact of medical and psychological treatments related to SCI. Literature reports that some co-morbidities are more prevalent in women with SCI compared with able-bodied women but data on sexual functioning are missing.Conclusion:To improve sexual rehabilitation services, sexual issues and response require evaluation during periodical check-ups using validated questionnaires administered by a physician ‘guide’ who coordinates professional operators thus providing personalized programmable interventions.

Clinical outcome of sacral neuromodulation in incomplete spinal cord-injured patients suffering from neurogenic bowel dysfunctions

Study design:Retrospective study.Objectives:Efficacy and safety of sacral neuromodulation (SNM) in incomplete spinal cord-injured patients (SCIPs) affected by chronic neurogenic bowel symptoms (NBSs).Setting:Neurourology Department. Primary to tertiary care.Methods:Retrospective non-blinded study without controls. Thirty-nine SCIPs were submitted to temporary stimulation for NBS. Permanent implantation was carried out if both their NBSs improved and the Wexner questionnaire scores were reduced by at least 50% during the first stage compared with that at baseline. Outcome measures included episodes of fecal incontinence and number of evacuations per week, as well as the Wexner score and the Short Form 36 (SF-36) Health Survey questionnaire.Results:Twenty-three SCIPs were submitted to definitive SNM, maintaining their clinical benefits after permanent implantation with a median follow-up of 38 months. The length of time since neurological diagnosis to SNM therapy represents the only factor related to the success of the implantation, P<0.05. In subjects with constipation (12), the median number of evacuations shifted from 1.65 to 4.98 per week, whereas the Wexner score changed from 19.91 to 6.82 in the final checkup with P<0.05. In subjects with fecal incontinence (11), the median number of episodes per week in the final follow-up was 1.32 compared with 4.55 pre-SNM. The general and mental health of both groups was measured with the SF-36 questionnaire and consistently showed statistical improvement (P<0.05).Anorectal manometry showed no important variation compared with baseline. There were no major complications.Conclusions:SNM therapy should be considered for the treatment of NBS for select patients with incomplete spinal cord injury when conservative treatments fail.

Treating erectile dysfunction and central neurological diseases with oral phosphodiesterase type 5 inhibitors. Review of the literature.

INTRODUCTION Erectile dysfunction (ED) is reported in a high percentage of patients with central neurological disorders (CND). AIM   An up-to-date review on oral phosphodiesterase 5 inhibitors (PDE5): sildenafil, tadalafil, and vardenafil for individuals with CND and ED. MAIN OUTCOME MEASURES Various questionnaires on ED, such as the International Index of Erectile Function composed of 15 questions. METHODS Internationally published clinical studies evaluating the efficacy and safety of PDE5 on subjects with CND and ED were selected. RESULTS Overall, 28 articles on PDE5 used to treat patients with CND and ED were included. With each of the three PDE5 compared to placebo or erectile baseline, literature reported significant statistical improvement (P < 0.01; P < 0.05) only in patients with spinal cord injury (SCI). PDE5 efficacy was documented for SCI patients up to 10 years. The most frequent predicable factor for PDE5 success was the presence of upper motoneuron lesion. Each of the three clinical sildenafil studies documented statistically significant improvement on erectile function in Parkinsons patients (P < 0.01; P < 0.05). Two studies reported discordant results about sildenafils effectiveness on multiple sclerosis (MS) patients; one on tadalafil showed significant statistical efficacy on erection versus baseline (P < 0.01; P < 0.05). The only spina bifida article determined that sildenafil remarkably improved erectile function. Overall, drawbacks were mostly slight-moderate, except in subjects with multiple system atrophy where sildenafil caused severe hypotension. CONCLUSIONS PDE5 represent first line ED therapy only for SCI patients, though treatment results through meta-analysis were not possible. Encouraging results are reported for Parkinsons and MS patients. PDE5 use for other CND patients is limited for various reasons, such as ED and concomitant libido impairment caused by depression and/or sexual endocrinology dysfunctions, and because PDE5 may cause a worsening of neurological illness. Medical centers staffed by health professionals able to counsel patients on the possible use of PDE5 are needed.

Diagnosis and therapy for neurogenic bladder dysfunctions in multiple sclerosis patients

Neurogenic lower urinary tract dysfunctions are common in patients with multiple sclerosis and for most of them urinary dysfunction has the most negative impact on their social life. No correlation exists between clinical urinary symptoms and urodynamic patterns. Abnormal urodynamic patterns may be present in asymptomatic patients. Both clinical and urodynamic findings may change during the course of the illness. Early diagnostic approach and scheduled follow-ups are mandatory in order to prevent upper urinary tract complications and improve quality of life (QoL).

Clinical concomitant benefits on pelvic floor dysfunctions after sacral neuromodulation in patients with incomplete spinal cord injury

Objectives:To assess the concomitant clinical improvement in incomplete spinal cord injury patients (SCIPs) suffering from neurogenic bowel symptoms (NBSs), neurogenic lower urinary tract symptoms (NLUTSs) and neurogenic erectile dysfunction (NED) using sacral neuromodulation (SNM) for NBSs and NLUTSs.Methods:Seventy-five SCIPs were selected. Before and during the follow-ups post-SNM, NLUTSs and NBSs were detected mainly through specific diaries. Erectile function was assessed using the International Index of Erectile Function composed of 5 questions (IIEF5). Quality of life (QoL) was measured with the Short Form 36 Health Survey questionnaire (SF-36). During the first stage, in which a permanent electrode was inserted percutaneously into the third sacral foramina and stimulated using an external generator, patients with NBSs or NLUTSs were required to improve their symptoms by at least 50% compared with baseline before proceeding to the second stage in which the generator was placed in the patients buttock. NED patients needed to increase their IIEF5 score by at least 25% compared with baseline (evaluated initially 3 months after the second stage) in order to continue follow-up.Results:Fourteen out of 37 subjects who manifested two functional pelvic dysfunctions at baseline maintained notable clinical improvement in two pelvic functions (median follow-up >3 years). Six had non-obstructive retention (NOR) and NED, six double incontinence, and two constipation with NOR. In the general and mental health domains of the SF-36, all patients improved their scores by at least 20% compared with baseline.Conclusions:SNM may be beneficial to selected incomplete SCIP with concomitant pelvic functional disturbances.

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.