Phosphodiesterase 5 Inhibitors for Erectile Dysfunction

International Journal of Clinical Practice, 2009

The American Journal of the Medical Sciences, 1995

with aging, which resulted in little attention being given to sexual behavior and treatment of sexual dysfunctions in the older population. However, in the current era it is known that as life expectancy improves, both men and women are seeking to preserve their sexuality into old age. While the appreciation of sexuality persists with aging, a decline in sexual activity is typically seen with, and can be attributed to both general health problems as well as specific sexual dysfunctions. In a large US study, the proportion of males who were sexually active declined from 83.7% in the age group 57-64 years to 38.5% in the age group 75-85 years . In a smaller pilot study in a cohort of 50 patients with a mean age of 81 years, Smith et al. reported that the main reason for being sexually inactive in older men was erectile dysfunction (ED), the condition defined as the persistent inability to attain and maintain penile erection sufficient for sexual intercourse . It is likely the most thoroughly studied sexual dysfunction in men and the most common sexual complaint of men presenting to their healthcare providers . The advent of safe oral therapy for the treatment of ED has brought attention to the disease and likely results in increased treatment-seeking behavior, also in the aging male. Despite the overwhelming success of these oral phosphodiesterase-5 inhibitors (PDE5I), the demand for pharmacotherapeutic and surgical options for ED continues to rise as a result of the increased proportion of elderly in the population as well as the increasing recognition that approximately one

Nature Clinical Practice Urology, 2005

PHARMACOKINETICS AND PHARMACO-DYNAMICS OF PDE-5 INHIBITORS Sildenafil Sildenafil is rapidly absorbed after oral administration, and has a terminal half-life of 3-5 h. Efficacy is optimal when taken on an empty stomach. The activity level is determined by the SUMMARY Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men. At present, first-line oral pharmacotherapy for most patients with ED is a phosphodiesterase type 5 (PDE-5) inhibitor, of which three are currently available worldwide. Sildenafil (Viagra®, Pfizer) has a very satisfactory efficacy-safety profile in all patient categories. The first PDE-5 inhibitor to reach the market, it is now the most widely prescribed oral agent for ED. Tadalafil (Cialis®, Lilly ICOS) and vardenafil (Levitra®, Bayer/GlaxoSmithKline) were introduced to the European Union and the US in 2003 and 2004, respectively. These three PDE-5 inhibitors share many characteristics, but each has unique features. This review describes the chemical, pharmacologic and clinical features of sildenafil, vardenafil and tadalafil as oral first-line treatments for ED. First, we describe the physiology of penile erection and PDE-5 inhibitor pharmacology, including chemistry, PDE selectivity, pharmacokinetics, and possible drug interactions. We then summarize data on the efficacy and safety profiles of the three PDE-5 inhibitors for the treatment of ED in the general population, in patients with diabetes mellitus and in men that have undergone bilateral nerve-sparing retropubic radical prostatectomy.

Erectile Dysfunction - Disease-Associated Mechanisms and Novel Insights into Therapy, 2012

International Journal of Impotence Research, 2002

Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has become a first-line therapy for diabetic patients with erectile dysfunction (ED). The efficacy in this subgroup, based on the Global Efficacy Question, is 56% vs 84% in a selected group of non-diabetic men with ED. Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in 'general' and diabetic study populations and are now candidates for US FDA approval. A summary analysis of the phase three clinical trials of sildenafil, tadalafil and vardenafil in both study populations is presented to provide a foundation on which the evaluation of the role of the individual PDE5 inhibitors for the treatment of patients with ED and DM can be built.

The Journal of Urology, 2004

Purpose: We quantified the prevalence of diagnosed hypertension, hyperlipidemia, diabetes mellitus and depression in male health plan members with erectile dysfunction (ED). Materials and Methods: We used a nationally representative managed care claims database that covered 51 health plans with 28 million lives for 1995 through 2002. Based on 272,325 identified patients with ED population and age specific prevalence rates were calculated for the same period. Results: The crude population prevalence rates were 41.6% for hypertension, 42.4% for hyperlipidemia, 20.2% for diabetes mellitus, 11.1% for depression, 23.9% for hypertension and hyperlipidemia, 12.8% for hypertension and diabetes mellitus, and 11.5% for hyperlipidemia and depression. The crude age specific prevalence rates varied across age groups significantly for hypertension (4.5% to 68.4%), hyperlipidemia (3.9% to 52.3%), and diabetes mellitus (2.8% to 28.7%), and significantly less for depression (5.8% to 15.0%). Region adjusted population prevalence rates were 41.2% for hypertension, 41.8% for hyperlipidemia, 19.7% for diabetes mellitus and 11.9% for depression. Only 87,163 patients with ED (32%) had no comorbid diagnosis of hypertension, hyperlipidemia, diabetes mellitus or depression. Conclusion: Hypertension, hyperlipidemia, diabetes mellitus and depression were prevalent in patients with ED. This evidence supported the proposition that ED shares common risk factors with these 4 concurrent conditions. Therefore, as a pathophysiological event, ED could be viewed as a potential observable marker for these concurrent diseases. This finding suggests that clinicians could include ED in the assessment profile of these concurrent conditions for earlier detection and treatment.

BJU International, 2012

To determine frequencies of, and risk factors for, ejaculatory dysfunction (EjD) and orgasmic dysfunction (OD) in men with different degrees of erectile dysfunction (ED). Baseline data from 28 ED trials were integrated and analysed. The International Index of Erectile Function Question 9 (IIEF-Q9; 'When you had sexual stimulation or intercourse, how often did you ejaculate?') and IIEF-Q10 ('How often did you have the feeling of orgasm with or without ejaculation?') were used to evaluate ejaculatory and orgasmic functions. Responses of 'almost never or never' or 'a few times (much less than half the time)' were taken as evidence of EjD or OD, respectively, whereas responses of 'almost always or always' or 'most times (much more than half the time)' were taken as evidence of normal function. Estimates of the relative risks (RRs) of EjD or OD were determined for multiple patient characteristics. Among 12,130 study participants with available data, only 5117 (42.2%) reported normal ejaculatory function, and 4321 (35.6%) normal orgasm, regardless of ED severity. Among subjects with poor ejaculatory function, 16.7% had mild ED, and among subjects with poor sensation of orgasm, 21.9% had mild ED. Frequencies of EjD and OD increased with increasing ED severity. Of the 5117 individuals with normal ejaculatory function, 796 (15.6%) had poor sensation of orgasm. Of the 4321 subjects with normal orgasm, 226 (5.2%) had poor ejaculatory function. Men with (vs without) EjD or OD tended to be younger: 53.7 vs 56.9 years and 54.2 vs 56.2 years, respectively. Factors associated with increased RRs of EjD and OD included cardiomyopathy (RR for EjD 1.74; RR for OD 1.59); cardiac failure (RR 1.40; 1.22); and baseline use (or history of use) of antipsychotics (RR 1.45; 1.30), selective serotonin reuptake inhibitors (RR 1.31; 1.27), and tricyclic antidepressants (RR 1.34; 1.28). EjD and OD occurred at baseline in more than one in three men enrolled in tadalafil trials. Even men with mild ED reported EjD or OD. Further studies are warranted to better understand the impacts of EjD and OD on male sexuality and quality of life.

Journal of Sexual Medicine, 2008

The Journal of Sexual Medicine, 2011

Introduction. Data from head-to-head clinical trials of phosphodiesterase type 5 (PDE5) inhibitors are scarce, making it difficult for clinicians to differentiate among these agents to select the most appropriate treatment for their patients with erectile dysfunction (ED). Aim. This randomized, double-blind, crossover head-to-head clinical trial compared patient preference, efficacy, and safety of vardenafil and sildenafil in men with ED and diabetes, hypertension, and/or hyperlipidemia. Methods. Prospective analysis was performed on two studies in which 1,057 men were randomized to vardenafil 20 mg (N = 530) or sildenafil 100 mg (2 × 50 mg encapsulated tablets) (N = 527) for 4 weeks. Following a 1-week washout, patients switched treatment for 4 weeks. Main Outcome Measures. Patients were asked about overall preference: "Overall, which medication do you prefer?", plus 11 other preference questions relating to their ED treatment. Efficacy assessments after each treatment period included the erectile function (EF) domain score of the International Index of Erectile Function (IIEF); Sexual Encounter Profile (SEP) diary questions SEP2 and SEP3; Global Assessment Question (GAQ); and Treatment Satisfaction Scale (TSS). Data regarding adverse events were collected throughout the study. Results. A total of 931 men (mean age 57.9 years) were included in the intent-to-treat (ITT) population. Noninferiority of vardenafil over sildenafil was achieved for overall preference (vardenafil 38.9%; sildenafil 34.5%; and no preference 26.6%). Additionally, the change from baseline in the EF domain score of the IIEF achieved nominal significance for vardenafil over sildenafil (10.00 vs. 9.40; P = 0.0052). Patients also had a higher percentage of positive responses for vardenafil for SEP2, SEP3, GAQ, and 12 of 19 questions on the TSS. Both drugs were well tolerated. Conclusions. This randomized, double-blind, head-to-head trial in ED patients with cardiovascular risk factors demonstrated noninferiority of vardenafil for overall preference. Vardenafil achieved nominal statistical superiority over sildenafil for several frequently used efficacy measures. Both drugs were well tolerated. Rubio-Aurioles E, Porst H, Eardley I, and Goldstein I for the Vardenafil-Sildenafil Comparator Study Group. Comparing vardenafil and sildenafil in the treatment of men with erectile dysfunction and risk factors for cardiovascular disease: A randomized, double-blind, pooled crossover study.

European Urology, 2002

UPDATE MARCH 2005 4 CONCLUSION 17 5 REFERENCES 18 6 ABBREVIATIONS USED IN THE TEXT 27 UPDATE MARCH 2005 3

International Journal of Impotence Research, 2002

The purpose of this research was to determine the prevalence of erectile dysfunction (ED) in a nonselected population using the abridged 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool. In a non-institutionalized population and during a free screening program for prostate cancer (Prostate Cancer Awareness Week of Santa Casa Hospital, Porto Alegre, Brazil), from 26 to 30 July 1998, all men who were attending were invited to complete a sexual activity questionnaire (the abridged 5-item version of the International Index of Erectile Function-IIEF-5) as a diagnostic tool for ED. The possible scores for the IIEF-5 range from 5 to 25, and ED was classified into five categories based on the scores: severe (5 -7), moderate (8 -11), mild to moderate (12 -16), mild (17 -21), and no ED (22 -25). Of the 1071 men who participated in the program, 965 (90.1%) were included in this study. Of the responding men 850 were Caucasian (88%) and 115 were black (12%). The mean age of the men was 60.7 y, ranging from 40 to 90 y old. In this sample the prevalence of all degrees of ED was estimated as 53.9%. In this group of men, the degree of ED was mild in 21.5%, mild to moderate in 14.1%, moderate in 6.3%, and severe in 11.9%. According to age the rates of ED were: , and over 80 y (100%) showed ED (P < 0.05). The Pearson coefficients between the variables age and IIEF-5 showed a statistically significant inverse (negative) relation (r ¼ 7 0.3449; P < 0.05). ED is highly prevalent in men over 40 and this condition showed a clear relationship to aging, as demonstrated in other studies published. The simplified IIEF-5, as a diagnostic tool, showed to be an easy method, which can be used to evaluate this condition in studies with a great number of men.

Indian Journal of Endocrinology and Metabolism, 2015

Background and Aims: Patients with diabetes mellitus frequently experience erectile dysfunction. This systematic review and meta-analysis were conducted to find efficacy and tolerability of phosphodiesterase 5 (PDE5) inhibitors in patients with diabetes mellitus experiencing erectile dysfunction. Methodology: Electronic searches were carried out to identify English language peer-reviewed randomized controlled trials (RCTs), which reported clinical efficacy of any PDE5 inhibitor in patients with diabetes mellitus having erectile dysfunction. Effect sizes were computed using Cohen's d, and I 2-test was used to assess heterogeneity. Pooled mean effect sizes were computed using random-effects model. Number needed to treat (NNT), and the adverse event rates were computed. Results: The systematic review included a total of 17 studies yielding 25 comparisons. Three studies were open RCTs while others were double-blind RCTs. The pooled mean effect size of any PDE5 inhibitor over placebo was 0.926 (95% confidence intervals [CI]: 0.864-0.987; I 2 = 26.3). The pooled mean effect size for sildenafil was 1.198 (CI: 1.039-1.357; I 2 = 0), for tadalafil was 0.910 (CI: 0.838-0.981; I 2 = 33.6), and for vardenafil was 0.678 (CI: 0.627-0.729; I 2 = 0). In pooled analysis, the NNT for sildenafil, tadalafil, vardenafil and any PDE5 inhibitor was 2.4, 2.6, 4.1 and 3.0 respectively. The most common side effects were headache, flushing, and nasal congestion. Conclusions: PDE5 inhibitors are effective and safe medications for the treatment of sexual dysfunction in patients with diabetes mellitus experiencing erectile dysfunction.

Drugs, 2008

The American Journal of Medicine, 2000

Up to 30 million men in the United States are affected by some degree of erectile dysfunction (ED). In the Massachusetts Male Aging Study (MMAS) 52% of men between 40 and 70 years of age were found to have some degree of ED. The MMAS and other studies also found that the likelihood of developing ED increases significantly with age. The vast majority of ED is primarily of organic and vascular cause, although psychological factors also play a role in most cases. ED has been shown to compromise overall quality of life and is associated with depression, anxiety, and loss of self-esteem. It may also signal serious underlying disease, including diabetes, hypertension, and cardiovascular disease. Therefore, questions regarding sexual functioning should be a routine part of the medical history. In the early 1990s, with the growing number of nonspecific and effective as well as less invasive tests, a new algorithm was developed that tailored evaluation to the treatment goals of the patient and his partner. This "goal-directed" approach simplifies the management of ED in the primary care setting; the availability of an effective oral agent, as well as a range of other therapeutic options, allows men with ED of all causes to receive effective treatment.

Clinical Interventions in Aging, 2009