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ABSTRACT: We compare the efficacy of testosterone gel (T-gel) versus placebo as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone.
A randomized, placebo controlled, double-blind, parallel group, multicenter study was performed. A total of 75 hypogonadal men (18 to 80 years old, morning serum total testosterone 400 ng/dl or less) with confirmed lack of response to sildenafil monotherapy were randomized (1:1) to receive a daily dose of 1% T-gel or 5 gm placebo gel as adjunctive therapy to 100 mg sildenafil during a 12-week period. Subjects were evaluated for sexual function, primarily based on the International Index of Erectile Function (IIEF), quality of life and serum testosterone levels at baseline and weeks 4, 8 and 12.
Testosterone treated subjects had greater improvement in erectile function compared to those who received placebo, reaching statistical significance at week 4 (4.4 vs 2.1, p = 0.029, 95.1% CI 0.3, 4.7). Similar trends were observed for improvements in orgasmic function, overall satisfaction, total IIEF score and percentage of IIEF responders. T-gel significantly (p < or = 0.004) increased total and free testosterone levels throughout the study, although no significant correlations were made between testosterone levels and the IIEF at end point.
T-gel taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who are unresponsive to sildenafil alone.
The Journal of urology 06/2008; 179(5 Suppl):S97-S102. · 4.02 Impact Factor
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ABSTRACT: To determine the minimal time to successful intercourse after taking sildenafil citrate for erectile dysfunction (ED).
Male patients with ED (mean age 60 years; mean ED duration 7.0 years) who were successfully treated with sildenafil (100 mg) for 2 months or longer were randomized to sildenafil (n = 115) or placebo (n = 113) for 4 weeks of double-blind treatment. Using a stopwatch, patients recorded the time needed to obtain an erection hard enough for sexual intercourse after taking the study drug at least 2 hours after eating.
Within 14 and 20 minutes of sildenafil dosing, 35% and 51% of sildenafil-treated patients, respectively, versus 22% and 30% of placebo-treated patients, respectively, had an erection that led to successful intercourse (P <0.05 for both). The median time to erection leading to successful intercourse after sildenafil dosing was 36 minutes compared with 141 minutes for placebo.
In this study, slightly more than one half of a population of prior sildenafil responders achieved an erection that led to successful sexual intercourse within 20 minutes of sildenafil administration, suggesting that the onset of action of sildenafil can be less than 30 minutes in men with ED.
Urology 09/2003; 62(3):400-3. · 2.43 Impact Factor
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ABSTRACT: In two multicenter, placebo controlled, phase 2 studies, patients with mild-to-moderate (n=161, Study 1) or severe (n=142, Study 2) erectile dysfunction (ED) were randomized to receive placebo, 0.05, 0.1, or 0.2 mg (Study 1) or placebo, 0.1, 0.2, or 0.3 mg (Study 2) of topically applied alprostadil (containing a proprietary skin permeation enhancer). The primary efficacy end point in both studies was the change in erectile function (EF) score from baseline to final visit. The changes from baseline for EF scores were -0.8+/-1.1, 1.8+/-1.1, 0.7+/-1.2, and 3.7+/-1.2 (P<0.01; Study 1) and 2.7+/-1.3, 6.29+/-1.4, 6.49+/-1.5, and 9.44+/-1.5 (P<0.001; Study 2) for ascending dose groups in each study. Topical alprostadil was well tolerated with the most common adverse event being urogenital pain. These results suggest this topical alprostadil formulation may be a potentially useful agent for the treatment of ED.
International Journal of Impotence Research 02/2003; 15(1):10-7. · 1.71 Impact Factor
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ABSTRACT: The objectives of this study were to evaluate long-term safety and efficacy of phentolamine mesylate, an orally active, rapid-acting alpha-adrenergic receptor antagonist, for the treatment of men suffering from erectile dysfunction (ED). It was an open-label study involving more than 2000 patients. Men received phentolamine mesylate 40 mg or 80 mg (10 tablets/month) as needed for up to 13 months and self-assessed erectile performance using two validated questionnaires. Treatment with phentolamine mesylate was associated with increases in Erectile Function Domain score of the IIEF, successful vaginal penetrations, and in overall satisfaction. Most adverse events were mild or moderate in severity and consistent with the known pharmacodynamic properties of phentolamine. In conclusion, phentolamine mesylate is safe and effective in the long-term treatment of men with mild to moderate ED.
International Journal of Impotence Research 09/2002; 14(4):266-70. · 1.71 Impact Factor
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ABSTRACT: Am J Hypertens (2002) 15, 143A–144A; doi:10.1016/S0895-7061(02)02664-X
P-313: Efficacy and safety of tadalafil in men with erectile dysfunction with and without hypertension
H. Padma-Nathan1,2,3,4,5,6, G. Brock1,2,3,4,5,6, C. McMahon1,2,3,4,5,6, K.K. Chen1,2,3,4,5,6, G. Anglin1,2,3,4,5,6, T. Costigan1,2,3,4,5,6, W. Shen1,2,3,4,5,6, V. Watkins1,2,3,4,5,6 and J.S. Whitaker1,2,3,4,5,61Keck School of Medicine, University of Southern California, Beverly Hills, CA, United States2University of Western Ontario, London, Ontario, Canada3St. Luke's Hospital, Sydney, Australia4Taipei Veterans General Hospital, Taipai, Taiwan5Eli Lilly, Indianapolis, IN, United States6ICOS Bothell, United States
American Journal of Hypertension 03/2002; · 3.18 Impact Factor
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ABSTRACT: Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.
International Journal of Impotence Research 08/2001; 13(4):192-9. · 1.71 Impact Factor
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ABSTRACT: Oral drugs are a well-established, first-line therapy for erectile dysfunction. As a result of the success of sildenafil, a plethora of new drugs for erectile dysfunction are on the horizon. Apomorphine and IC351 are in late phase III development. Vardenafil (Bayer, New Haven, CT), a PDE5 inhibitor, and the combination of yohimbine and L-arginine (NitroMed, Boston, MA) are in early phase III development. Early clinical and preclinical studies are investigating new phosphodiesterase inhibitors, cyclic AMP activators, alpha-adrenergic antagonists, dopamine agonists, melanocyte-stimulating hormone, potassium channel modulators, endothelin antagonists, and new nitric oxide donors. The future is bright for this infant field of sexual pharmacotherapy.
Urologic Clinics of North America 06/2001; 28(2):321-34. · 1.82 Impact Factor
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ABSTRACT: IC351 (Cialis) is a selective inhibitor of PDE5. The efficacy and safety of on-demand dosing of IC351 in men with erectile dysfunction was assessed in a multicenter, double-blind, placebo-controlled study. One hundred seventy-nine men (mean age: 56 y) were randomized to receive placebo or IC351 at doses of 2, 5, 10 or 25 mg, taken on demand over a 3-week period. The primary endpoints were change from baseline in responses to Questions 3 (Q3) and 4 (Q4) of the International Index of Erectile Function (IIEF). IC351 significantly improved IIEF Q3 scores at all doses vs placebo (P < or =0.003). IC351 also significantly improved IIEF Q4 scores in all but the 2 mg group (P < or =0.0003). No significant changes in laboratory values, ECGs, or blood pressure were observed. The most common adverse events were headache and dyspepsia. The conclusion of this study was that on-demand IC351 at doses up to 25 mg was well tolerated and significantly improved erectile function.
International Journal of Impotence Research 02/2001; 13(1):2-9. · 1.71 Impact Factor
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H Padma-Nathan
International Journal of Impotence Research 10/2000; 12 Suppl 3:S56-7. · 1.71 Impact Factor
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H Padma-Nathan
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ABSTRACT: The new era of erectile dysfunction medicine ushered in by the availability of an effective and safe oral medication paves the evolution of the field toward a multi-disciplinary and primary care setting. There exists a paucity of guidelines regarding the assessment and management of the patient with erectile dysfunction in the primary care arena. The 'Process of Care' model for the evaluation and treatment of erectile dysfunction has been developed to advance new guidelines for the diagnosis and management of erectile dysfunction in the primary care and multi-disciplinary setting. This model was developed under the auspices of the University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School (chairman: R Rosen) with input from a multi-disciplinary group of experts including representation from primary care, internal medicine, endocrinology, psychiatry, psychology and urology. The methodology employed was a modified delphi-technique (RAND method). The key components of the model are: 1)a rational approach to diagnosis and treatment, 2) emphasis on clinical history-taking and a focused physical examination 3) specialized testing and referral in pre-defined situations 4) step-wise management approach with ranking of treatment options and 5)incorporation of patient and partner needs and preferences in the decision making process when possible (a goal-directed approach). The management algorithm is conceptually organized into progressive stages from Process--> Action--> Outcome. International Journal of Impotence Research (2000) 12, Suppl 4, S119-S121.
International Journal of Impotence Research 10/2000; 12 Suppl 4:S119-21. · 1.71 Impact Factor
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ABSTRACT: The purpose of the study was to utilize axial penile buckling testing as a primary efficacy variable of erection quality during multi-institutional in-office dose titration testing with alprostadil alfadex, prostaglandin E1 (PGE1)-alpha-cyclodextrin, (EDEX /VIRIDAL, Schwarz Pharma) in patients with erectile dysfunction. In 41 study sites, in three different dose titration studies involving 894 patients with impotence >6 months, a buckling test was performed and repeated every 10 min for up to 60 min, within 30 min following alprostadil alfadex administration, or when two consecutive circumference measurements reached maximum values. The buckling device consisted of a standard weight scale attached to a 2 inch diameter plastic cap with a concavity on its ventral surface (H. Eric Richards, Inc., Canton MA). A positive test was associated with absent penile shaft buckling to a downward force of 1.0 kg, slowly applied to the glans in the axis of the erect shaft. A total of 630 (71%) patients experienced at least one positive buckling test. Three consecutive positive buckling tests, implying a functionally rigid erection for at least 20 min, were noted in 521 (58%) patients. There were high correlations between the presence of three consecutive positive buckling tests following alprostadil alfadex injection and the patient's (83% of cases) and the investigator's (88% of cases) evaluation of adequacy of erection for intercourse. Similarly, there were high correlations between the presence of negative buckling tests and the patient's (95% of cases) and the investigator's (96% of cases) evaluation of inadequacy of erection for intercourse. The axial penile buckling test offers a simple, reliable, and inexpensive method to objectively quantify erectile response following in-office dose titration of intracavernosal alprostadil alfadex. The high correlation to subjective patient/investigator assessment adds to the validity of the test.
International Journal of Impotence Research 08/2000; 12(4):205-11. · 1.71 Impact Factor
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R DeBusk,
Y Drory,
I Goldstein,
G Jackson,
S Kaul,
S E Kimmel,
J B Kostis,
R A Kloner,
M Lakin,
C M Meston,
M Mittleman,
J E Muller, H Padma-Nathan,
R C Rosen,
R A Stein,
R Zusman
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ABSTRACT: Sexual dysfunction is highly prevalent in both sexes and adversely affects patients' quality of life and well being. Given the frequent association between sexual dysfunction and cardiovascular disease, in addition to the potential cardiac risk of sexual activity itself, a consensus panel was convened to develop recommendations for clinical management of sexual dysfunction in patients with cardiovascular disease. Based upon a review of the research and presentations by invited experts, a classification system was developed for stratification of patients into high, low, and intermediate categories of cardiac risk. The large majority of patients are in the low-risk category, which includes patients with (1) controlled hypertension; (2) mild, stable angina; (3) successful coronary revascularization; (4) a history of uncomplicated myocardial infarction (MI); (5) mild valvular disease; and (6) no symptoms and <3 cardiovascular risk factors. These patients can be safely encouraged to initiate or resume sexual activity or to receive treatment for sexual dysfunction. An important exception is the use of sildenafil in patients taking nitrates in any form. Patients in the intermediate-risk category include those with (1) moderate angina; (2) a recent MI (<6 weeks); (3) left ventricular dysfunction and/or class II congestive heart failure; (4) nonsustained low-risk arrhythmias; and (5) >/=3 risk factors for coronary artery disease. These patients should receive further cardiologic evaluation before restratification into the low- or high-risk category. Finally, patients in the high-risk category include those with (1) unstable or refractory angina; (2) uncontrolled hypertension; (3) congestive heart failure (class III or IV); (4) very recent MI (<2 weeks); (5) high-risk arrhythmias; (6) obstructive cardiomyopathies; and (7) moderate-to-severe valvular disease. These patients should be stabilized by specific treatment for their cardiac condition before resuming sexual activity or being treated for sexual dysfunction. A simple algorithm is provided for guiding physicians in the management of sexual dysfunction in patients with varying degrees of cardiac risk.
The American Journal of Cardiology 08/2000; 86(2):175-81. · 3.37 Impact Factor
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ABSTRACT: The new era of erectile dysfunction (ED) medicine ushered in by the availability of an effective and safe oral medication paves the way toward managing ED in a primary care setting. The Process of Care Model for the Evaluation and Treatment of Erectile Dysfunction was developed to advance new guidelines for the diagnosis and management of ED. This paper discusses these guidelines.
The Nurse Practitioner 07/2000; Suppl:4-10; quiz 19-20.
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H Padma-Nathan
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ABSTRACT: In treating erectile dysfunction (ED) effectively, a hierarchy of treatments based on efficacy, safety, and other factors can be a valuable instrument for assisting clinical decisions. First-line therapies, in this hierarchy, include sildenafil--the only orally administered erectogenic drug currently available--vacuum constriction devices, and psychological counseling and sexual therapy. Second-line therapies include intracavernous injection and intraurethral suppositories. Third-line therapies include penile implant surgery. This article presents a broad overview of all available therapies, but concentrates on sildenafil as the current paradigm of broadly efficacious, safe, and convenient treatment for ED.
Postgraduate Medicine 06/2000; 107(6 Suppl Educational):14-8. · 1.78 Impact Factor
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ABSTRACT: Sildenafil (Viagra), an oral treatment for erectile dysfunction, has proved popular since its introduction in 1998. However, not all patients respond to this form of therapy. Consequently, this study investigated the efficacy of intracavernous alprostadil alfadex (EDEX/VIRIDAL) treatment in patients not responding to sildenafil.
In an open-label, multicenter study, patients with erectile dysfunction were treated with sildenafil for 4 weeks. The initial dose was 50 mg, which was increased to 100 mg if no response was achieved. Patients not responding to treatment, measured using the International Index of Erectile Function (IIEF) questionnaire, entered an alprostadil alfadex in-office titration phase, to determine the optimal dose, up to 40 microgram. A 6-week alprostadil alfadex at-home treatment phase followed.
In 67 patients who did not respond satisfactorily to sildenafil, the alprostadil alfadex at-home therapy resulted in improvements in questions 3 and 4 of the IIEF in 60 (89.6%) and 57 (85.1%) patients, respectively. The mean improvement in IIEF score for these patients was 2.75 and 2.63 for questions 3 and 4, respectively. The most common side effect was penile pain in 25 (29. 4%) of 85 patients treated with alprostadil alfadex in-office and at home.
Alprostadil alfadex therapy can be used effectively and safely in men who fail initial therapy with sildenafil.
Urology 05/2000; 55(4):477-80. · 2.43 Impact Factor
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R Basson,
J Berman,
A Burnett,
L Derogatis,
D Ferguson,
J Fourcroy,
I Goldstein,
A Graziottin,
J Heiman,
E Laan,
S Leiblum, H Padma-Nathan,
R Rosen,
K Segraves,
R T Segraves,
R Shabsigh,
M Sipski,
G Wagner,
B Whipple
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ABSTRACT: Female sexual dysfunction is highly prevalent but not well defined or understood. We evaluated and revised existing definitions and classifications of female sexual dysfunction.
An interdisciplinary consensus conference panel consisting of 19 experts in female sexual dysfunction selected from 5 countries was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease. A modified Delphi method was used to develop consensus definitions and classifications, and build on the existing framework of the International Classification of Diseases-10 and DSM-IV: Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, which were limited to consideration of psychiatric disorders.
Classifications were expanded to include psychogenic and organic causes of desire, arousal, orgasm and sexual pain disorders. An essential element of the new diagnostic system is the "personal distress" criterion. In particular, new definitions of sexual arousal and hypoactive sexual desire disorders were developed, and a new category of noncoital sexual pain disorder was added. In addition, a new subtyping system for clinical diagnosis was devised. Guidelines for clinical end points and outcomes were proposed, and important research goals and priorities were identified.
We recommend use of the new female sexual dysfunction diagnostic and classification system based on physiological as well as psychological pathophysiologies, and a personal distress criterion for most diagnostic categories.
The Journal of Urology 04/2000; 163(3):888-93. · 3.75 Impact Factor
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ABSTRACT: To compare the efficacy, safety, and patient preference of intracavernously administered alprostadil alfadex and intraurethrally administered alprostadil.
A crossover, randomized, open-label multicenter study of 111 patients with erectile dysfunction of at least 6 months' duration compared the efficacy, safety, and patient preference of intracavernosal alprostadil (EDEX/Viridal) with MUSE plus optional ACTIS. All patients underwent an in-office dose titration with either drug before undertaking an at-home treatment phase. The most frequently used doses during the at-home phase were 40 microg (44.1% of men) and 1000 microg (86.8% of men) for EDEX and MUSE, respectively; the mean doses were 26.1 microg and 922.5 microg for EDEX and MUSE, respectively.
More EDEX than MUSE administrations resulted in an erection sufficient for sexual intercourse (82.5% versus 53.0%); significantly more patients using EDEX achieved at least one erection sufficient for sexual intercourse (92.6% versus 61.8%; P <0.0001); and EDEX use resulted in a significantly greater percentage of patients attaining at least 75% of erections sufficient for sexual intercourse (75% versus 36.8%; P <0.0001). Penile pain was the most common side effect for both medications: 20.0% versus 30.5% (in-office) and 33.8% versus 25.0% (at-home) for EDEX and MUSE, respectively. Similar numbers of adverse events were reported with either treatment during the at-home phase. Patient and partner satisfaction was greater with EDEX, and more patients preferred this therapy, choosing to continue it during a patient preference period at the end of the study.
Since intracavernous injection therapy was more efficacious, better tolerated, and preferred by the patients and their partners, it should be offered as the first-choice treatment if oral therapy fails or is contraindicated.
Urology 02/2000; 55(1):109-13. · 2.43 Impact Factor
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H Padma-Nathan
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ABSTRACT: The recent introduction of sildenafil has revolutionized the treatment of erectile dysfunction (ED). The availability of sildenafil, the first effective oral agent for ED, has also expanded the field of sexual healthcare to include general and primary care practitioners and other nonurology specialists. A new process-of-care algorithm has been developed to facilitate the evaluation and treatment of ED in these nonurology settings. Sildenafil has been demonstrated to be safe and effective in randomized, double-blind, placebo-controlled trials involving >3,000 men ages 19-87 years. Sildenafil is effective across a broad range of etiologies including diabetes. For patients in whom first-line treatment with sildenafil fails or ceases to be effective, second-line interventions with intracavernosal self-injection therapy or transurethral alprostadil may be indicated. In addition to sildenafil, other oral agents such as oral phentolamine and sublingual apomorphine are now in clinical trials. Drugs under development include second-generation phosphodiesterase type 5 (PDE5) inhibitors, endothelin antagonists, and agents that offer specific molecular targeting. Clinical studies are also being planned to examine the efficacy of combination oral drug regimens for ED.
The American Journal of Cardiology 10/1999; 84(5B):18N-23N. · 3.37 Impact Factor
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H Padma-Nathan
International journal of clinical practice. Supplement 07/1999; 102:13-5.
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ABSTRACT: We evaluated the hemodynamic effects of transurethral alprostadil in 21 patients with erectile dysfunction using color duplex ultrasonography.
Penile arterial diameter, peak flow velocity and end diastolic velocity were compared following intraurethral administration of 500 microg. alprostadil and intracavernosal injection of 10 microg. alprostadil.
A dose of 500 microg. transurethral alprostadil resulted in significant increases in corporeal blood flow comparable to those achieved with intracavernosal injection of 10 microg. alprostadil as measured by duplex ultrasonography in men with erectile dysfunction. Transurethral alprostadil resulted in statistically significant increases in arterial diameter and peak flow velocity comparable to those achieved with intracavernosal injection. End diastolic velocities were higher after transurethral alprostadil than intracavernosal injections. Color ultrasonography following transurethral alprostadil showed arterial and venous hyperemia of the corpus spongiosum and corpora cavernosa. Furthermore, color ultrasonography revealed communicating vessels between the corpus spongiosum and corpora cavernosa following administration of transurethral alprostadil.
The visualization of communicating vessels between the corpus spongiosum and corpora cavernosa after transurethral alprostadil suggests local mechanisms of drug transfer from one to the other. In addition to potential clinical benefits, transurethral alprostadil may be useful to visualize the vascular anatomy of the penis and to test for patient responsiveness to local vasoactive agents.
The Journal of Urology 11/1998; 160(4):1321-4. · 3.75 Impact Factor
