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Re: Addition of Metformin to Sildenafil Treatment for Erectile Dysfunction in Eugonadal Non-Diabetic Men With Insulin Resistance. A Prospective, Randomized, Double Blind Pilot Study
MALE AND FEMALE SEXUAL FUNCTION AND DYSFUNCTION; ANDROLOGY
Re: Time to Onset of Action of Vardenafil: A Retrospective Analysis of the Pivotal Trials for the Orodispersible and Film-Coated Tablet Formulations F. M. Debruyne, M. Gittelman, H. Sperling, M. Börner and M. Beneke Andros Mannenkliniek, Arnhem, The Netherlands J Sex Med 2011; 8: 2912–2923.
Introduction: Patients and physicians consider a rapid onset of action to be an important attribute of oral pharmacotherapy for erectile dysfunction. Aim: To investigate the time to onset of action of a new orodispersible tablet (ODT) formulation of vardenafil. Methods: A post hoc integrated analysis was performed on data from two 12-week, double-blind, multicenter, randomized, parallel-group, placebocontrolled phase III trials of 10 mg vardenafil ODT. Data for the vardenafil film-coated tablet were generated from a retrospective integrated analysis at week 12 of four double-blind, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled phase III trials. Time intervals (in 15-, 30-, and 60-minute increments, up to ⱖ6 hours after study medication intake) were determined for the period between dosing and start of sexual activity (with the intention of intercourse). Main Outcome Measures: The total number of sexual intercourse attempts and Sexual Encounter Profile question 3 (SEP3) success rates were calculated per time interval. Results: Within 15 minutes postdosing, mean per-patient SEP3 success rates were 62.5% (vardenafil ODT) vs. 29.4% (placebo), with corresponding overall SEP3 success rates of 59.8% and 38.2%. In this time interval, 5.3% vs. 2.8% of all sexual activity attempts were initiated by subjects taking vardenafil ODT (n ⫽ 89) or placebo (n ⫽ 62), respectively. At 16-30 minutes postdosing, SEP3 success rates were 65.3% and 32.6% (mean perpatient) and 70.2% and 51.0% (overall) for vardenafil ODT vs. placebo, respectively, with a corresponding 10.4% and 8.7% of all sexual activity attempts being made by subjects taking vardenafil ODT (n ⫽ 170) or placebo (n ⫽ 118). Comparable results were observed for vardenafil 10 and 20 mg film-coated tablet at corresponding time intervals. Conclusions: Vardenafil ODT shows a rapid onset of action comparable with that of vardenafil film-coated tablet. In those men who begin sexual activity within 30 minutes after dosing, the majority of sexual attempts lead to successful intercourse. Editorial Comment: This new formulation of vardenafil is placed on the tongue. It appears to dissolve quickly and is rapidly absorbed, making it a bit unique. The data suggest that a significant number of patients will be able to achieve erections sufficient for intercourse within 15 to 30 minutes of taking this new medication. The data also suggest a low side effect profile and similar erection efficacy compared to the standard 10 mg vardenafil dose. Thus, this new formulation, which is currently available in the United States, may be of interest to men or couples looking for a phosphodiesterase 5 inhibitor with relatively rapid onset and comparable erection efficacy when judged against historical oral phosphodiesterase 5 inhibitor preparations. Allen D. Seftel, M.D.
Re: Addition of Metformin to Sildenafil Treatment for Erectile Dysfunction in Eugonadal Non-Diabetic Men With Insulin Resistance. A Prospective, Randomized, Double Blind Pilot Study G. J. Rey Valzacchi, P. R. Costanzo, L. A. Finger, A. O. Layus, G. M. Gueglio, L. E. Litwak and P. Knoblovits J Androl 2011; Epub ahead of print.
Erection depends largely on the release of nitric oxide (NO) by vascular endothelial cells. Insulin resistance (IR) is a metabolic abnormality that produces endothelial dysfunction characterized by decreased synthesis and release of NO. Aim: To evaluate the effect of treatment with metformin on the response to sildenafil in patients with erectile dysfunction (ED) and IR. Methods: Prospective, randomized, controlled, double-blind placebo study. We included 30 male patients with ED, IR and
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MALE AND FEMALE SEXUAL FUNCTION AND DYSFUNCTION; ANDROLOGY
poor response to sildenafil. Exclusion criteria: pharmacologic, anatomic or endocrine ED, diabetes, prostatic surgery or chronic illnesses. Erectile function was rated according to the International Index of Erectile Function 5 (IIEF-5). IR was measured by HOMA (IR⫽HOMA ⱖ3). Patients were randomized to receive metformin (n⫽17) or placebo (n⫽13). Results: After treatment with metformin, patients with ED showed a significant increase in IIEF-5 score and a significant decrease in HOMA both occurring at months 2 (IIEF-5: 17.0⫾6.0 vs. 14.3⫾3.9, p⫽0.01 and Homa: 3.9⫾1.6 vs. 5.5⫾2.4, p⫽0.01) to 4 of treatment (IIEF-5: 19.8⫾3.8 vs. 14.3⫾3.9, p⫽0.005 and Homa: 4.5⫾1.9 vs. 5.5⫾2.4, p⫽0.04), with no changes in these parameters in patients with ED receiving placebo. Patients treated with metformin had more adverse events than those who received placebo: 61.5% versus 7.7%, p⫽0.03, respectively. AEs were mild, mainly gastrointestinal, and did not cause discontinuation of treatment. Conclusion: Treatment with metformin in patients with ED and poor response to sildenafil reduced the IR and improved erectile function. Editorial Comment: This is a prospective, randomized, controlled, double-blind placebo study. The authors included 30 males with ED, insulin resistance and poor response to sildenafil. Exclusion criteria consisted of pharmacological, anatomical or endocrine ED, diabetes, prostatic surgery and chronic illnesses. Erectile function was rated according to the IIEF-5. Insulin resistance was measured by homeostasis model assessment (IR ⴝ HOMA 3 or greater). Patients were randomized to receive metformin (17 patients) or placebo (13). At 2 and 4 months following treatment with metformin patients with ED showed a significant increase in IIEF-5 score (mean ⴞ SD 17.0 ⴞ 6.0 [p ⴝ 0.01] and 19.8 ⴞ 3.8 [p ⴝ 0.005], respectively) compared to baseline (14.3 ⴞ 3.9), as well as a significant decrease in HOMA (3.9 ⴞ 1.6 [p ⴝ 0.01] and 4.5 ⴞ 1.9 [p ⴝ 0.04], respectively) compared to baseline (5.5 ⴞ 2.4), while there were no changes in these parameters in the placebo group. Patients treated with metformin had more adverse events (61.5%) than those receiving placebo (7.7%, p ⴝ 0.03). Adverse events were mild, were mainly gastrointestinal and did not cause discontinuation of treatment. It would be important to understand if these short-term benefits in erection improvement were sustained and how well metformin was tolerated in the long term. Allen D. Seftel, M.D.
Re: Correlates of PDE5i Use Among Subjects With Erectile Dysfunction in Two Population-Based Surveys T. G. Travison, S. A. Hall, W. A. Fisher, A. B. Araujo, R. C. Rosen, J. B. McKinlay and M. S. Sand Department of Epidemiology, New England Research Institutes, Inc., Watertown, Massachusetts J Sex Med 2011; 8: 3051–3057.
Introduction: Erectile dysfunction (ED) is thought to affect some 150 million men worldwide, but many men with ED symptoms do not seek treatment. Existing surveys suggest that men with severe ED and who report support from their partners are more likely to receive treatment than were others. Less is known, however, concerning the influence of sociomedical factors such as income and body composition on receipt of treatment. Aim: The aim of this study was to determine the importance of socioeconomic status, comorbidities, and body composition on receipt of treatment for ED symptoms. Methods: We used data on 638 men enrolled in the Boston Area Community Health (BACH) survey reporting ED symptoms and/or treatment for ED as evidenced by phosphodiesterase type 5 inhibitor (PDE5i) use. Logistic regression was employed to assess the relative strength of association between receipt of treatment and socioeconomic factors, body mass index, and medical factors. A replication of these results was then provided via a parallel model using the 2004 follow-up of the Men’s Attitudes to Life Events and Sexuality (MALES). Main Outcome Measure: In BACH, ED was deemed present if a subject scored 16 points or fewer on the five-item International Index of Erectile Function or reported PDE5i use. In MALES, presence of ED was indicated by use of a validated single question
Re: Time to Onset of Action of Vardenafil: A Retrospective Analysis of the Pivotal Trials for the Orodispersible and Film-Coated Tablet Formulations F. M. Debruyne, M. Gittelman, H. Sperling, M. Börner and M. Beneke Andros Mannenkliniek, Arnhem, The Netherlands J Sex Med 2011; 8: 2912–2923.
Introduction: Patients and physicians consider a rapid onset of action to be an important attribute of oral pharmacotherapy for erectile dysfunction. Aim: To investigate the time to onset of action of a new orodispersible tablet (ODT) formulation of vardenafil. Methods: A post hoc integrated analysis was performed on data from two 12-week, double-blind, multicenter, randomized, parallel-group, placebocontrolled phase III trials of 10 mg vardenafil ODT. Data for the vardenafil film-coated tablet were generated from a retrospective integrated analysis at week 12 of four double-blind, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled phase III trials. Time intervals (in 15-, 30-, and 60-minute increments, up to ⱖ6 hours after study medication intake) were determined for the period between dosing and start of sexual activity (with the intention of intercourse). Main Outcome Measures: The total number of sexual intercourse attempts and Sexual Encounter Profile question 3 (SEP3) success rates were calculated per time interval. Results: Within 15 minutes postdosing, mean per-patient SEP3 success rates were 62.5% (vardenafil ODT) vs. 29.4% (placebo), with corresponding overall SEP3 success rates of 59.8% and 38.2%. In this time interval, 5.3% vs. 2.8% of all sexual activity attempts were initiated by subjects taking vardenafil ODT (n ⫽ 89) or placebo (n ⫽ 62), respectively. At 16-30 minutes postdosing, SEP3 success rates were 65.3% and 32.6% (mean perpatient) and 70.2% and 51.0% (overall) for vardenafil ODT vs. placebo, respectively, with a corresponding 10.4% and 8.7% of all sexual activity attempts being made by subjects taking vardenafil ODT (n ⫽ 170) or placebo (n ⫽ 118). Comparable results were observed for vardenafil 10 and 20 mg film-coated tablet at corresponding time intervals. Conclusions: Vardenafil ODT shows a rapid onset of action comparable with that of vardenafil film-coated tablet. In those men who begin sexual activity within 30 minutes after dosing, the majority of sexual attempts lead to successful intercourse. Editorial Comment: This new formulation of vardenafil is placed on the tongue. It appears to dissolve quickly and is rapidly absorbed, making it a bit unique. The data suggest that a significant number of patients will be able to achieve erections sufficient for intercourse within 15 to 30 minutes of taking this new medication. The data also suggest a low side effect profile and similar erection efficacy compared to the standard 10 mg vardenafil dose. Thus, this new formulation, which is currently available in the United States, may be of interest to men or couples looking for a phosphodiesterase 5 inhibitor with relatively rapid onset and comparable erection efficacy when judged against historical oral phosphodiesterase 5 inhibitor preparations. Allen D. Seftel, M.D.
Re: Addition of Metformin to Sildenafil Treatment for Erectile Dysfunction in Eugonadal Non-Diabetic Men With Insulin Resistance. A Prospective, Randomized, Double Blind Pilot Study G. J. Rey Valzacchi, P. R. Costanzo, L. A. Finger, A. O. Layus, G. M. Gueglio, L. E. Litwak and P. Knoblovits J Androl 2011; Epub ahead of print.
Erection depends largely on the release of nitric oxide (NO) by vascular endothelial cells. Insulin resistance (IR) is a metabolic abnormality that produces endothelial dysfunction characterized by decreased synthesis and release of NO. Aim: To evaluate the effect of treatment with metformin on the response to sildenafil in patients with erectile dysfunction (ED) and IR. Methods: Prospective, randomized, controlled, double-blind placebo study. We included 30 male patients with ED, IR and
1787
1788
MALE AND FEMALE SEXUAL FUNCTION AND DYSFUNCTION; ANDROLOGY
poor response to sildenafil. Exclusion criteria: pharmacologic, anatomic or endocrine ED, diabetes, prostatic surgery or chronic illnesses. Erectile function was rated according to the International Index of Erectile Function 5 (IIEF-5). IR was measured by HOMA (IR⫽HOMA ⱖ3). Patients were randomized to receive metformin (n⫽17) or placebo (n⫽13). Results: After treatment with metformin, patients with ED showed a significant increase in IIEF-5 score and a significant decrease in HOMA both occurring at months 2 (IIEF-5: 17.0⫾6.0 vs. 14.3⫾3.9, p⫽0.01 and Homa: 3.9⫾1.6 vs. 5.5⫾2.4, p⫽0.01) to 4 of treatment (IIEF-5: 19.8⫾3.8 vs. 14.3⫾3.9, p⫽0.005 and Homa: 4.5⫾1.9 vs. 5.5⫾2.4, p⫽0.04), with no changes in these parameters in patients with ED receiving placebo. Patients treated with metformin had more adverse events than those who received placebo: 61.5% versus 7.7%, p⫽0.03, respectively. AEs were mild, mainly gastrointestinal, and did not cause discontinuation of treatment. Conclusion: Treatment with metformin in patients with ED and poor response to sildenafil reduced the IR and improved erectile function. Editorial Comment: This is a prospective, randomized, controlled, double-blind placebo study. The authors included 30 males with ED, insulin resistance and poor response to sildenafil. Exclusion criteria consisted of pharmacological, anatomical or endocrine ED, diabetes, prostatic surgery and chronic illnesses. Erectile function was rated according to the IIEF-5. Insulin resistance was measured by homeostasis model assessment (IR ⴝ HOMA 3 or greater). Patients were randomized to receive metformin (17 patients) or placebo (13). At 2 and 4 months following treatment with metformin patients with ED showed a significant increase in IIEF-5 score (mean ⴞ SD 17.0 ⴞ 6.0 [p ⴝ 0.01] and 19.8 ⴞ 3.8 [p ⴝ 0.005], respectively) compared to baseline (14.3 ⴞ 3.9), as well as a significant decrease in HOMA (3.9 ⴞ 1.6 [p ⴝ 0.01] and 4.5 ⴞ 1.9 [p ⴝ 0.04], respectively) compared to baseline (5.5 ⴞ 2.4), while there were no changes in these parameters in the placebo group. Patients treated with metformin had more adverse events (61.5%) than those receiving placebo (7.7%, p ⴝ 0.03). Adverse events were mild, were mainly gastrointestinal and did not cause discontinuation of treatment. It would be important to understand if these short-term benefits in erection improvement were sustained and how well metformin was tolerated in the long term. Allen D. Seftel, M.D.
Re: Correlates of PDE5i Use Among Subjects With Erectile Dysfunction in Two Population-Based Surveys T. G. Travison, S. A. Hall, W. A. Fisher, A. B. Araujo, R. C. Rosen, J. B. McKinlay and M. S. Sand Department of Epidemiology, New England Research Institutes, Inc., Watertown, Massachusetts J Sex Med 2011; 8: 3051–3057.
Introduction: Erectile dysfunction (ED) is thought to affect some 150 million men worldwide, but many men with ED symptoms do not seek treatment. Existing surveys suggest that men with severe ED and who report support from their partners are more likely to receive treatment than were others. Less is known, however, concerning the influence of sociomedical factors such as income and body composition on receipt of treatment. Aim: The aim of this study was to determine the importance of socioeconomic status, comorbidities, and body composition on receipt of treatment for ED symptoms. Methods: We used data on 638 men enrolled in the Boston Area Community Health (BACH) survey reporting ED symptoms and/or treatment for ED as evidenced by phosphodiesterase type 5 inhibitor (PDE5i) use. Logistic regression was employed to assess the relative strength of association between receipt of treatment and socioeconomic factors, body mass index, and medical factors. A replication of these results was then provided via a parallel model using the 2004 follow-up of the Men’s Attitudes to Life Events and Sexuality (MALES). Main Outcome Measure: In BACH, ED was deemed present if a subject scored 16 points or fewer on the five-item International Index of Erectile Function or reported PDE5i use. In MALES, presence of ED was indicated by use of a validated single question