Publications by authors named "Harin Padma-nathan"

24 Publications

  • Page 1 of 1

Return of nocturnal erections and erectile function after bilateral nerve-sparing radical prostatectomy in men treated nightly with sildenafil citrate: subanalysis of a longitudinal randomized double-blind placebo-controlled trial.

J Sex Med 2008 Feb 14;5(2):476-84. Epub 2007 Dec 14.

New York University Medical Center-Urology, New York, NY, USA.

Introduction: After bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP), nocturnal and sexually mediated erections may help to preserve normal erectile function (EF).

Aim: To investigate nocturnal penile tumescence and rigidity (NPTR) in a subset (N = 54 men) from a randomized, double-blind trial (N = 76) of nightly sildenafil after BNSRRP.

Methods: Inclusion required preoperative "normal" EF (defined as a combined score of >/=8 for International Index of Erectile Function questions 3 (penetration) and 4 (maintained erection after penetration) and NPTR testing (>/=10 continuous minutes of >/=55% rigidity [R >/= 55%] at the base). Postoperative assessments were at weeks 4 (pretreatment), 16, 28, 40 (during 36 weeks of nightly prophylaxis: sildenafil 50 mg [N = 17], 100 mg [N = 18] or placebo [N = 19]), and 48 (after 8 weeks of no erectile dysfunction therapy, when "responders" were delineated by the defined normal EF and a "yes" response to "Over the past 4 weeks, have your erections been good enough for satisfactory sexual activity?"). Base and tip rigidity and tumescence were measured using penile plethysmography.

Main Outcome Measures: Duration of R >/= 55% and area under the curves for rigidity and tumescence.

Results: Postoperatively, rapid profound reduction in nocturnal EF was noted in all groups. There was a gradual dose-dependent improvement in base and tip rigidity in the sildenafil groups but little improvement in the placebo group. Eight weeks after treatment termination (48 weeks postoperatively), 24% (4/17) of 50-mg sildenafil recipients, 33% (6/18) of 100-mg sildenafil recipients, and 5% (1/19) of placebo recipients were responders. Tip R >/= 55% was the most discriminating NPTR measure between nonresponders and responders to sildenafil, in whom it regained baseline (preoperative) levels (whereas base R >/= 55% did not). It was most prolonged in responders to sildenafil 100 mg.

Conclusions: In our subset analysis, nightly sildenafil for 9 months post-BNSRRP objectively improved nocturnal erections and pharmaceutically unassisted EF.
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http://dx.doi.org/10.1111/j.1743-6109.2007.00700.xDOI Listing
February 2008

Vardenafil restores erectile function to normal range in men with erectile dysfunction.

J Sex Med 2007 Jan;4(1):152-161

Bayer Inc., Toronto, Canada.

Introduction: The ability of oral phosphodiesterase type 5 (PDE5) inhibitor therapy to restore erectile function to normal is an important attribute to men with erectile dysfunction (ED).

Aim: To assess the ability of vardenafil to restore normal erectile function in men with general ED.

Methods: In two fixed-dose, parallel-group, double-blind, placebo-controlled, pivotal studies, patients received vardenafil (5, 10, or 20 mg) or placebo for 12/26 weeks.

Main Outcome Measure: In this retrospective analysis, the percentage of patients "returning to normal" erectile function at week 12 (as defined by scores > or =26 on erectile function domain of International Index of Erectile Function [IIEF-EF]) was determined, with further stratification by baseline ED severity, etiology, age, and duration of ED.

Results: Vardenafil 5, 10, and 20 mg returned 32%, 43%, and 49% of patients, respectively, to normal erectile function after 12 weeks, compared with 10% of patients receiving placebo (P < 0.0001). Return to normal IIEF-EF domain scores was noted irrespective of severity, etiology, age, and duration of ED, and was observed even in challenging-to-treat subgroups. With vardenafil 20 mg, 39% of men with severe ED at baseline, 45-49% of men with ED of mixed or organic etiology, 35% of men aged > or =65 years, and 43% of men with ED of > or =3 years of duration returned to normal erectile function at week 12. Mean per-patient SEP3 (question 3 on the Sexual Encounter Profile) success rates in patients achieving IIEF-EF domain scores > or =26 ranged from 87% to 95%.

Conclusion: Vardenafil improves the IIEF-EF domain score to the normal range in a substantial proportion of men with ED.
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http://dx.doi.org/10.1111/j.1743-6109.2006.00380.xDOI Listing
January 2007

Erectile function and assessments of erection hardness correlate positively with measures of emotional well-being, sexual satisfaction, and treatment satisfaction in men with erectile dysfunction treated with sildenafil citrate (Viagra).

Urology 2006 Sep;68(3 Suppl):26-37

Department of Urology, Università Vita e Salute San Raffaele, Milan, Italy.

We aimed to determine whether erectile function (EF) and assessments of erection hardness correlate positively with measures of psychosocial outcomes (ie, emotional well-being, sexual satisfaction, and satisfaction with erectile dysfunction [ED] treatment) in men treated with sildenafil citrate (Viagra; Pfizer Inc, New York, NY). Data were collected from 33 worldwide phase 2, 3, and 4 sildenafil clinical trials, which included almost 10,000 men with ED. Most of these trials were randomized, double-blind, and placebo-controlled (n = 27) and were undertaken to assess doses of 50 mg adjustable to 25 mg or 100 mg, depending on efficacy and tolerability (n = 32). Doses were taken approximately 1 hour before anticipated sexual activity but not more often than once daily. EF was assessed with use of the EF domain of the International Index of Erectile Function (IIEF) and with assessments of erection hardness (Erection Hardness Grading Scale [EHGS] and IIEF Q2 [the frequency of erections hard enough for penetration]). Change (baseline to end point) in emotional well-being in men treated for ED was assessed with the Self-Esteem and Relationship (SEAR) questionnaire, which consisted of the Confidence domain (ie, the Self-Esteem subscale and Overall Relationship subscale) and the Sexual Relationship domain. End point treatment satisfaction (overall, speed of onset, and duration of action) was assessed with the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). The IIEF was used to assess change and end point sexual satisfaction by means of the Intercourse Satisfaction domain, Q7 (frequency of satisfactory sexual intercourse), and the Overall Satisfaction domain (ie, Q13, satisfaction with sex life, and Q14, satisfaction with sexual relationship). In men treated with sildenafil for ED, scores for measures of EF (IIEF EF domain, IIEF Q2) and the percentage of erections graded completely hard and fully rigid (EHGS grade 4) correlated positively with scores for measures of psychosocial outcomes (SEAR emotional well-being, IIEF sexual satisfaction, and EDITS ED treatment satisfaction), indicating that when EF improved and erection hardness increased, these measures of psychosocial function also improved.
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http://dx.doi.org/10.1016/j.urology.2006.06.027DOI Listing
September 2006

PDE-5 Inhibitor Therapy for Erectile Dysfunction Secondary to Nerve-Sparing Radical Retropubic Prostatectomy.

Rev Urol 2005 ;7 Suppl 2:S33-8

The majority of patients receiving therapy for erectile dysfunction (ED) following post-radical retropubic prostatectomy (RRP) are treated with phosphodiesterase (PDE)-5 inhibitors, which seem to have variable efficacy in this population. So far, the only head-to-head trials with PDE-5 inhibitors have been in general ED patients and not in post-RRP patients. Both vardenafil and tadalafil failed to meet statistical noninferiority to sildenafil in head-to-head trials. To date, only sildenafil has demonstrated efficacy in the prevention of post-nerve-sparing RRP ED. The selection of a PDE-5 inhibitor requires consideration of the patient's sexual activity pattern as well as the drug's efficacy and its ability to meet the patient's expectations. In this regard, sildenafil continues to account for almost 70% of PDE-5 inhibitor prescriptions in the United States.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477594PMC
July 2011

An integrated analysis of alprostadil topical cream for the treatment of erectile dysfunction in 1732 patients.

Urology 2006 Aug;68(2):386-91

The Keck School of Medicine of the University of Southern California, The Male Clinic, Beverly Hills, California 90212, USA.

Objective: To assess the safety and efficacy of topical alprostadil cream for erectile dysfunction (ED).

Methods: Patients with an ED score of 25 or less on the erectile function domain of the International Index of Erectile Function (IIEF) were randomly assigned to placebo or topical alprostadil cream (100, 200, or 300 microg) for at-home use for 12 weeks in two multicenter, double-blind, parallel-group studies. Patients receiving organic nitrates and patients with diabetes were included. Primary end points included the change in score for the erectile function domain of the IIEF and the change from baseline for the Sexual Encounter Profile (SEP) questions 2 (vaginal penetration success) and 3 (maintenance of erection to ejaculation). Safety was based on observed and reported adverse events and clinical laboratory results. Data from each study were pooled into a single integrated analysis.

Results: A total of 1732 patients received placebo (n = 434) or topical alprostadil cream at 100 microg (n = 434), 200 microg (n = 430), or 300 microg (n = 434). The mean changes from baseline to end point in IIEF erectile function (EF) domain scores were -0.7, 1.6, 2.5, and 2.4 points for each group, respectively (P <0.001). Scores on SEP questions 2 and 3 improved slightly but significantly for all drug treatment groups compared with placebo (P <0.001). Most adverse events were localized to the application site and resolved within 2 hours.

Conclusions: Topical alprostadil cream significantly improves ED in a broad range of patients. Most adverse events were limited to the application site and were generally well tolerated.
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http://dx.doi.org/10.1016/j.urology.2006.02.027DOI Listing
August 2006

An integrated analysis of alprostadil topical cream for the treatment of erectile dysfunction in 1732 patients.

Urology 2006 Aug;68(2):386-91

The Keck School of Medicine of the University of Southern California, The Male Clinic, Beverly Hills, California 90212, USA.

Objective: To assess the safety and efficacy of topical alprostadil cream for erectile dysfunction (ED).

Methods: Patients with an ED score of 25 or less on the erectile function domain of the International Index of Erectile Function (IIEF) were randomly assigned to placebo or topical alprostadil cream (100, 200, or 300 microg) for at-home use for 12 weeks in two multicenter, double-blind, parallel-group studies. Patients receiving organic nitrates and patients with diabetes were included. Primary end points included the change in score for the erectile function domain of the IIEF and the change from baseline for the Sexual Encounter Profile (SEP) questions 2 (vaginal penetration success) and 3 (maintenance of erection to ejaculation). Safety was based on observed and reported adverse events and clinical laboratory results. Data from each study were pooled into a single integrated analysis.

Results: A total of 1732 patients received placebo (n = 434) or topical alprostadil cream at 100 microg (n = 434), 200 microg (n = 430), or 300 microg (n = 434). The mean changes from baseline to end point in IIEF erectile function (EF) domain scores were -0.7, 1.6, 2.5, and 2.4 points for each group, respectively (P <0.001). Scores on SEP questions 2 and 3 improved slightly but significantly for all drug treatment groups compared with placebo (P <0.001). Most adverse events were localized to the application site and resolved within 2 hours.

Conclusions: Topical alprostadil cream significantly improves ED in a broad range of patients. Most adverse events were limited to the application site and were generally well tolerated.
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http://dx.doi.org/10.1016/j.urology.2006.02.027DOI Listing
August 2006

Determining the earliest time within 30 minutes to erectogenic effect after tadalafil 10 and 20 mg: a multicenter, randomized, double-blind, placebo-controlled, at-home study.

J Sex Med 2004 Sep;1(2):193-200

Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Introduction: Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor used for the treatment of erectile dysfunction (ED). The minimal time to onset of erectogenic effect in the at-home setting has not been evaluated.

Aim: The goal was to determine the earliest time to erectogenic effect leading to successful intercourse within 30 minutes after taking tadalafil 10 and 20 mg.

Methods: The multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase-2 study enrolled men at least 21 years old with a minimum 3-month history of ED. Four single doses each of placebo, tadalafil 10 mg, or 20 mg were taken at home once every 8-10 days. Using a stopwatch, couples recorded in Sexual Encounter Profile diaries the earliest time within 30 minutes after dosing to the first erection adequate for vaginal penetration, and whether the erection led to successful intercourse.

Main Outcome Measures: The primary analysis compared the percentage of erections resulting in successful intercourse between tadalafil groups and placebo at one-minute intervals using a step-down procedure. A secondary analysis compared the overall distribution of time to erectogenic effect between treatment groups using the Cox Regression Method.

Results: Compared to placebo, a significant erectogenic response to tadalafil 20 mg was found from 30 minutes down to 16 minutes after dosing (P = 0.012). Response to tadalafil 10 mg approached significance (P = 0.054) at 30 minutes. As analysed by the Cox Regression Method, a significant erectogenic response was found from 30 minutes down to 15 minutes after dosing for tadalafil 20 mg (P = 0.020), and from 30 minutes down to 26 minutes for tadalafil 10 mg (P = 0.042). Fifty-two percent of men taking tadalafil 20 mg had at least one successful intercourse attempt within 30 minutes compared to 35.1% of men taking placebo (P = 0.038).

Conclusions: This stopwatch-based study demonstrated a pharmacodynamic effect within 30 minutes after dosing for tadalafil 10 and 20 mg.
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http://dx.doi.org/10.1111/j.1743-6109.2004.04028.xDOI Listing
September 2004

Earliest time to onset of action leading to successful intercourse with vardenafil determined in an at-home setting: a randomized, double-blind, placebo-controlled trial.

J Sex Med 2004 Sep;1(2):168-78

Department of Urology, Universita Vita Salute San Raffaele, Milan, Italy.

Introduction: Vardenafil, a potent and selective oral PDE5 inhibitor, is efficacious and generally well-tolerated in men with erectile dysfunction (ED). Of considerable interest to patients and physicians is an understanding of the time required after dosing to attain penile erection sufficient for successful sexual intercourse.

Aim: To determine the earliest time to onset of action of vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in men with ED.

Methods: A prospective, randomized, double-blind, parallel-group, at-home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in North America and Europe. Following a 4-week run-in period, patients were randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N = 247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the elapsed time from dosing to attainment of an erection perceived to be adequate for penetration that led to intercourse completion. Earliest time of onset was defined as the fastest time among the first four doses for each patient. Time points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a backward stepping procedure.

Results: Mean baseline erectile function domain score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of men on vardenafil 10/20 mg had at least one erection in the first four doses perceived to be sufficient for penetration with subsequent intercourse completion compared to 26% on placebo (P < 0.0001). A statistically superior response to vardenafil vs. placebo was observed in these responders at all times >or= 10 and >or= 11 minutes (P < 0.025) in the 10 and 20 mg groups, respectively. In a retrospective analysis using time intervals of
Conclusion: In this large, at-home study, the onset of action of vardenafil with subsequent intercourse completion was recognized as early as 10 minutes after dosing.
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http://dx.doi.org/10.1111/j.1743-6109.2004.04025.xDOI Listing
September 2004

Pharmacotherapy for erectile dysfunction.

J Sex Med 2004 Sep;1(2):128-40

Introduction: Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction.

Aim: To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction.

Methods: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries.

Main Outcome Measure: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate.

Results: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation.

Conclusions: There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.
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http://dx.doi.org/10.1111/j.1743-6109.2004.04021.xDOI Listing
September 2004

Erectile dysfunction is a marker for cardiovascular disease: results of the minority health institute expert advisory panel.

J Sex Med 2005 Jan;2(1):40-50; discussion 50-2

The Epicenter for Sexual Health & Medicine, University of Minnesota School of Medicine, Minneapolis, USA.

Introduction: Cardiovascular disease and its related comorbidities are associated with significant morbidity and mortality and affect a disproportionately large number of African Americans and Hispanics. The prevalence of cardiovascular disease is increasing worldwide, which underscores the urgency to improve methods of prevention and early detection.

Aim: To develop a risk assessment and management algorithm for primary care patients with erectile dysfunction (ED) that facilitates diagnosis, early intervention, and prevention of cardiovascular disease.

Methods: The Minority Health Institute (MHI) convened an Expert Advisory Panel of cardiologists and urologists to design a new practice model algorithm that uses ED as a clinical tool for early identification of men with systemic vascular disease. A draft of the algorithm was presented at a national symposium and comments from symposium participants were considered in the development of the final algorithm.

Main Outcome Measures And Results: Erectile dysfunction is common and has long been considered a secondary complication of cardiovascular disease, diabetes, hypertension, and dyslipidemia. However, a growing body of evidence challenges this view, suggesting instead that ED is an early manifestation of atherosclerosis and a precursor to systemic vascular disease. Endothelial dysfunction is the etiologic factor linking ED and cardiovascular disease.

Conclusions: The recognition of ED as an early sign of systemic cardiovascular disease offers an opportunity for prevention, particularly in high-risk and underserved minority populations. The MHI algorithm stipulates that all men 25 years old and older regardless of sexual dysfunction complaints should be asked about ED. The presence of ED should prompt an aggressive assessment for cardiovascular risk and occult systemic vascular disease.
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http://dx.doi.org/10.1111/j.1743-6109.2005.20104_1.xDOI Listing
January 2005

Erectile dysfunction secondary to nerve-sparing radical retropubic prostatectomy: comparative phosphodiesterase-5 inhibitor efficacy for therapy and novel prevention strategies.

Curr Urol Rep 2004 Dec;5(6):467-71

Male Clinic, Beverly Hills, CA 90210, USA.

Postprostatectomy erectile dysfunction appears to be initiated by neuropraxia and perpetuated by cavernosal smooth muscle apoptosis. Phosphodiesterase-5 (PDE-5) inhibitor therapy is the current cornerstone of erectile dysfunction (ED) therapy in this population. Although no head-to-head trials have been performed with sildenafil, vardenafil, and tadalafil in this population, there are numerous studies in the general ED population. The results of these studies demonstrate that neither of the new PDE-5 inhibitors met statistical noninferiority to sildenafil. Sildenafil has been studied in a novel primary prevention modality using nightly administration after a bilateral nerve-sparing prostatectomy. In this novel approach, it effected a sevenfold improvement in return of spontaneous, normal erectile function 2 months after drug discontinuation. This effect appears to be mediated by properties unique to sildenafil that include improved endothelial function and neuronal regeneration and neuroprotection. In primary prevention, unlike ED therapy, one has only "one shot" by definition. Therefore, it is even more critical to apply evidence-based medicine.
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http://dx.doi.org/10.1007/s11934-004-0072-0DOI Listing
December 2004

Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial.

J Urol 2004 Sep;172(3):1036-41

Department of Urology, Universita Vita Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy.

Purpose: We evaluated the efficacy and safety of tadalafil 20 mg, taken on demand, in men with erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy (BNSRRP).

Materials And Methods: This randomized, double-blind, placebo controlled multicenter study consisted of a 4-week treatment-free run-in period (baseline) followed by 12 weeks of treatment. A total of 303 men (mean age 60 years) with preoperative normal erectile function who had undergone a BNSRRP 12 to 48 months before study were randomized (2:1) to tadalafil (201) or placebo (102). The 3 co-primary end points were changes from baseline in the International Index of Erectile Function erectile function domain score, and the percentage of positive responses to Sexual Encounter Profile questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question and the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary end points. We defined a priori a subgroup of 201 patients reporting evidence of postoperative tumescence, defined as 50% or greater "yes" responses to Sexual Encounter Profile question 1 (ability to achieve at least some erection) during baseline intercourse attempts and stratified randomization based on this criterion.

Results: Patients receiving tadalafil reported greater improvement on all primary and secondary end points (p <0.001) compared to placebo. For all randomized patients and for the subgroup with evidence of postoperative tumescence, the mean International Index of Erectile Function erectile function domain score increased for patients receiving tadalafil (mean +/- SEM 5.3 +/- 0.5 and 5.9 +/- 0.7, respectively, p <0.001 vs placebo for both). For all randomized patients who received tadalafil, the mean percentage of successful penetration attempts was 54% and the mean percentage of successful intercourse attempts was 41%. For the subgroup with evidence of postoperative tumescence these values were 69% and 52%, respectively. Of all patients randomized to tadalafil 62% and of the subgroup patients randomized to tadalafil 71% reported improved erections. Patients receiving tadalafil reported greater treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction than those receiving placebo. Headache (21%), dyspepsia (13%) and myalgia (7%) were the most commonly reported adverse events.

Conclusions: Tadalafil 20 mg, taken on-demand, was an efficacious and well tolerated treatment for erectile dysfunction following BNSRRP.
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http://dx.doi.org/10.1097/01.ju.0000136448.71773.2bDOI Listing
September 2004

Roundtable discussion: tadalafil study group.

Am J Cardiol 2003 Nov;92(9A):58M-65M

Division of Cardiovascular Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

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http://dx.doi.org/10.1016/s0002-9149(03)00826-9DOI Listing
November 2003

Efficacy and tolerability of tadalafil, a novel phosphodiesterase 5 inhibitor, in treatment of erectile dysfunction.

Am J Cardiol 2003 Nov;92(9A):19M-25M

Male Clinic, Beverly Hills, California, USA.

Advances in molecular biology and protein chemistry, along with increasing understanding of the mechanisms of penile erection, have spurred development of pharmacologic approaches to the treatment of erectile dysfunction (ED). The next generation of oral agents includes tadalafil, a potent, highly selective phosphodiesterase 5 inhibitor. In vitro studies have shown that tadalafil enhances relaxation of trabecular smooth muscle, and clinical trials have supported its efficacy and tolerability in a broad population of men with ED. The effect of tadalafil in enhancing the erectile response to sexual stimulation is relatively rapid in onset and lasts for >or=24 hours. The ability of patients with ED treated with tadalafil to achieve improved erectile function is demonstrated by significantly increased subjective measures of penetration ability, successful intercourse, and sexual satisfaction. Partners have expressed similar or higher levels of satisfaction with the results of treatment. Men with ED of psychogenic, organic, or mixed etiology and in a range from mild to severe have experienced significant improvment with tadalafil treatment. Response to treatment in men with diabetes has been robust and not affected by disease severity. Tadalafil has been well tolerated. Adverse events have generally been mild or moderate and have abated with continued treatment. Headache and dyspepsia have been most frequently reported. Changes in color vision have been rare (<0.1%) with tadalafil across all clinical trials. Tadalafil appears to be a safe and effective treatment for men with ED.
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http://dx.doi.org/10.1016/s0002-9149(03)00828-2DOI Listing
November 2003

Efficacy and safety of topical alprostadil cream for the treatment of female sexual arousal disorder (FSAD): a double-blind, multicenter, randomized, and placebo-controlled clinical trial.

J Sex Marital Ther 2003 Oct-Dec;29(5):329-44

The Male Clinic, Beverly Hills, California, USA.

We evaluated the efficacy and safety of three doses of a novel alprostadil cream in a randomized, double-blind, placebo-controlled study in 94 women presenting with female sexual arousal disorder of at least 6 month s duration. We sent the subjects home with 10 premeasured doses of 500 g, 1000 g, or 1500 g alprostadil or a placebo cream to be applied to the vulvar area prior to vaginal intercourse over a period of 6 weeks. The primary efficacy parameter, the arousal success rate (as measured by diary responses to the Female Sexual Encounter Profile [FSEP]), was highest in the alprostadil 1000 g group and lowest in the 500 g group, but the responses were not different from that of the placebo cream, at the p = 0.05 level, for any of the three alprostadil doses. However, the change from baseline for Item 6 of the Female Sexual Function Index (FSFI; Rosen et al., 2000; satisfaction with arousal during sexual activity) suggested an important dose-related trend (p = 0.173; 1500 g versus placebo). The mean percent responder rate (responder = > 50% arousal success rate with > 3 sexual attempts) suggested a dose-response effect (p = 0.157; 1500 g versus placebo). Adverse events were generally mild or moderate in intensity and mainly involved localized reactions in the genital area.
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http://dx.doi.org/10.1080/00926230390224710DOI Listing
March 2004

Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy.

J Urol 2003 Oct;170(4 Pt 1):1278-83

St. Joseph's Medical Center, Lawson Research Institute, London, Ontario, Canada.

Purpose: More than one-third of men may experience erectile dysfunction (ED) after nerve sparing radical retropubic prostatectomy. The efficacy and safety of vardenafil, a potent, selective, phosphodiesterase 5 inhibitor, was assessed for the treatment of ED after radical prostatectomy.

Materials And Methods: In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were randomized to take placebo, or 10 or 20 mg vardenafil. Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function, diary questions measuring vaginal penetration and intercourse success rates, and a global assessment question (GAQ) on erection.

Results: Of the intent to treat population 70% had severe ED (erectile function less than 11) at baseline. After 12 weeks both vardenafil doses were significantly superior to placebo (p <0.0001) for all efficacy variables. Improved erections (based on GAQ) were reported by 65.2% and 59.4% of patients on 20 and 10 mg vardenafil, respectively, and by only 12.5% of patients on placebo (p <0.0001). Among men with bilateral neurovascular bundle sparing, positive GAQ responses were reported by 71.1% and 59.7% of patients on 20 and 10 mg vardenafil, respectively, versus 11.5% of those on placebo (p <0.0001). The average intercourse success rate per patient receiving 20 mg vardenafil was 74% in men with mild to moderate ED and 28% in men with severe ED, compared to 49% and 4% for placebo, respectively. Few adverse events were observed. They were generally mild to moderate headache, flushing and rhinitis.

Conclusions: In men with severe ED after nerve sparing radical retropubic prostatectomy, vardenafil significantly improved key indices of erectile function.
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http://dx.doi.org/10.1097/01.ju.0000086947.00547.49DOI Listing
October 2003

Erectile dysfunction in the cardiac patient: how common and should we treat?

J Urol 2003 Aug;170(2 Pt 2):S46-50; discussion S50

Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd., Los Angeles, California 90017, USA.

Purpose: Risk factors for erectile dysfunction (ED) (hypertension, diabetes, smoking, lipid abnormality) are also risk factors for coronary artery disease. However, most cardiologists do not routinely ask about ED and patients often are reluctant or embarrassed to discuss it. We determined how common ED was in a group of patients with chronic stable coronary artery disease.

Materials And Methods: We administered the validated Sexual Health Inventory for Men (SHIM) 5-item questionnaire, based on the International Index of Erectile Function questionnaire, to 76 men with chronic stable coronary artery disease during routine outpatient cardiology visits. Most of these men had not previously discussed ED with their cardiologist.

Results: The mean patient age was 64 years (range 40 to 82). The questionnaire took about 5 minutes to complete. Of the patients 47% were on beta blockers, 92% statins, 28% diuretics. SHIM score was 21 or less in 53 men (70%), which is indicative of ED. Of the patients 75% had some difficulty achieving erections (question 2) and 67% had some difficulty maintaining an erection after penetration (question 3). The questionnaire reflected successful sildenafil treatment in 4 patients (SHIM scores 23 to 25). If these 4 men are included as having had ED then 57 of 76 (75%) had ED or recent history of ED.

Conclusions: ED is extremely common in men with chronic coronary artery disease (affecting approximately 75%) yet most cardiologists do not ask about it. The SHIM is a useful, quick and inexpensive tool for discussion and diagnosis of ED in this population. Although it is well established that cardiovascular risk factors are associated with erectile dysfunction, once it is present there is mixed information on whether treating the risk factors will treat the ED. Problems appear to be that lifestyle modification in midlife may simply be too late to effect a change, and some antihypertensive and lipid lowering drugs may actually exacerbate ED. Oral therapy for ED, namely the PDE5 inhibitors, is effective and safe in most cardiac and hypertensive patients. Organic nitrates such as nitroglycerin remain a contraindication to the concomitant use of these drugs. Guidelines for treatment of ED in the cardiac patient issued by the American College of Cardiology/American Heart Association and Princeton Guidelines may be useful in the approach to the cardiac patient with ED.
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http://dx.doi.org/10.1097/01.ju.0000075055.34506.59DOI Listing
August 2003

Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial.

Urology 2003 Jul;62(1):121-5; discussion 125-6

Private Urological Practice, Hamburg, Germany.

Objectives: To examine the therapeutic effects of tadalafil on erectile dysfunction (ED) at 24 and 36 hours after dosing.

Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 348 men (mean age 57 years) with ED was conducted in Europe and the United States. Patients were stratified by baseline severity of ED using the Erectile Function domain score of the International Index of Erectile Function and then randomly allocated within the severity group to receive tadalafil 20 mg (n = 175) or placebo (n = 173). Subsequently, participants were randomly assigned to two 4-week treatment intervals, during which they were requested to attempt sexual intercourse approximately 24 or 36 hours after tadalafil or placebo dosing. The primary outcome measure was the proportion of successful sexual intercourse attempts (completed to ejaculation) according to patient self-report using the Sexual Encounter Profile diary.

Results: Of the 348 patients, 327 (94%) completed the trial (163 of 175 in the tadalafil group and 164 of 173 in the placebo group). Thirty-six hours after tadalafil dosing, 59.2% of intercourse attempts were successful versus 28.3% in the placebo group (P <0.001). The proportion of successful intercourse attempts at approximately 24 hours after treatment was also significantly greater with tadalafil (52.9%) than with placebo (29.1%; P <0.001). Tadalafil was well tolerated. The incidences of four treatment-emergent adverse events were significantly greater in the tadalafil group than in the placebo group (all P <0.05): headache, flushing, dyspepsia, and myalgia.

Conclusions: Tadalafil 20 mg is an effective and well-tolerated treatment for ED that has a period of responsiveness of up to 36 hours.
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http://dx.doi.org/10.1016/s0090-4295(03)00359-5DOI Listing
July 2003

Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial.

Urology 2003 Apr;61(4 Suppl 1):8-14

Department of Urology, Tulane University Medical Center, New Orleans, Louisiana 70112, USA.

The durability of key efficacy response parameters and safety of vardenafil was evaluated in a pivotal trial conducted in a broad population of men with erectile dysfunction (ED) in North America. In this randomized, double-blind, placebo-controlled, multicenter, fixed-dose, parallel-group, 6-month comparison study, men >18 years of age with ED for >6 months received 5-mg, 10-mg, and 20-mg doses of vardenafil as needed for up to 26 weeks. The primary efficacy variables were the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain scores, and the Sexual Encounter Profile (SEP) mean per-patient success rates for penetration (SEP question 2) and maintenance of erections (SEP question 3). Safety data were also collected over time. Improvement in all primary efficacy variables was observed in all vardenafil groups versus placebo. These improvements occurred early and were either sustained or increased through week 26. Vardenafil in 10-mg and 20-mg doses was significantly superior to placebo at all time points for all efficacy variables (P <0.01), and all doses were superior to placebo at endpoint (P <0.001). Most treatment-emergent adverse events (headache, flushing, dyspepsia, and rhinitis) were mild or moderate in intensity, and incidence generally decreased over time. All 3 doses of vardenafil were superior to placebo across all primary efficacy variables and all study time points in a broad range of patients with ED, regardless of etiology or severity. Vardenafil was well tolerated. These results demonstrate that vardenafil provides sustained efficacy with reduced incidence of nuisance side effects over time. High resolution video, medium resolution video, low resolution video.
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http://dx.doi.org/10.1016/s0090-4295(03)00115-8DOI Listing
April 2003

Topical alprostadil cream for the treatment of erectile dysfunction: a combined analysis of the phase II program.

Urology 2002 Dec;60(6):1077-82

Northeast Indiana Research, Fort Wayne, Indiana, USA.

Objectives: To present a meta-analysis of the efficacy and safety data of two recently completed Phase II studies examining a novel alprostadil topical cream for the treatment of erectile dysfunction (ED).

Methods: Patients (n = 303) with ED of at least 3 months' duration were randomized to receive placebo or 50, 100, 200, or 300 microg alprostadil in two nearly identical 11-dose, multicenter, at-home studies of a novel topical cream containing alprostadil and a proprietary skin permeation enhancer. The primary efficacy endpoint was the change in erectile function domain score from baseline to the final visit. Secondary endpoints included changes in scores for questions 3 and 4 of the International Index of Erectile Function and standard diary analyses. Safety was assessed by analysis of adverse events, changes in laboratory test results, and physical examination findings.

Results: The mean baseline parameters for the erectile function score, ED history, and secondary diagnoses suggested no significant differences among the treatment groups. The changes from baseline to the final visit erectile function scores were 0.98 +/- 0.84, 3.4 +/- 1.3, 3.4 +/- 0.88 (P <0.05), 5.3 +/- 0.92 (P <0.001), and 9.4 +/- 1.43 (P <0.001) for the ascending dose groups. Most secondary efficacy endpoints were significant for the 200 and 300-microg dose groups. Dose-related trends in efficacy were observed. Adverse events were localized to the application site, were of mild or moderate intensity, and were of short duration.

Conclusions: These results suggest topical alprostadil cream, when combined with a novel dermal permeation-enhancer, to be a potentially useful agent for the treatment of ED.
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http://dx.doi.org/10.1016/s0090-4295(02)01980-5DOI Listing
December 2002

A 4-year update on the safety of sildenafil citrate (Viagra).

Urology 2002 Sep;60(2 Suppl 2):67-90

The Male Clinic, Keck School of Medicine at the University of Southern California School of Medicine, Beverly Hills, California, USA.

Clinical studies have demonstrated that sildenafil citrate (Viagra) is an effective and well-tolerated oral treatment for erectile dysfunction. Despite its established safety profile, concern about its cardiovascular safety persists among some physicians and the general public. This concern has stemmed primarily from sporadic reports of adverse events published in the literature and sensationalized by the media. However, the only absolute contraindication for sildenafil is concurrent use of nitrates. Because sildenafil has been on the market for 4 years and under clinical investigation for even longer, we can now evaluate its long-term safety in men who have been taking the drug for several years. We review this issue from 3 perspectives. First, we reassess the overall safety profile of sildenafil by reviewing the initial controlled clinical trials and open-label studies. We present new data from patients who have been exposed to sildenafil for up to 4.5 years. We also evaluate the results from independent postmarketing studies. Second, we review the cardiovascular-specific results from the clinical trials, long-term extension, and postmarketing studies. Lastly, we review the specific effects on the visual system based on findings from studies conducted during drug development and post marketing.
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http://dx.doi.org/10.1016/s0090-4295(02)01752-1DOI Listing
September 2002

Introduction. The management of erectile dysfunction (ED).

Urology 2002 Sep;60(2 Suppl 2):1-3

The Male Clinic, the Keck School of Medicine at the University of Southern California School of Medicine, Beverly Hills, California, USA.

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http://dx.doi.org/10.1016/s0090-4295(02)01685-0DOI Listing
September 2002

Vardenafil for treatment of men with erectile dysfunction: efficacy and safety in a randomized, double-blind, placebo-controlled trial.

J Androl 2002 Nov-Dec;23(6):763-71

Department of Urology, Tulane University Medical Center, New Orleans, Louisiana 70112, USA.

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May 2003