Oral Phosphodiesterase-5 Inhibitors Research Articles

A Pilot Study of an Oral Phosphodiesterase Inhibitor (Apremilast) for Atopic Dermatitis in Adults

To investigate the preliminary safety and efficacy of apremilast, an oral phosphodiesterase 4 inhibitor, for atopic dermatitis. This investigator-initiated, open-label pilot study evaluated 2 doses of apremilast in patients with atopic dermatitis. Differential gene analysis was performed from peripheral whole blood using data before and after treatment. University-based dermatology clinical research unit. Sixteen adult patients with atopic dermatitis. A specific phosphodiesterase 4 inhibitor, apremilast. The primary outcome was incidence of adverse events. Secondary outcomes included the differences in pruritus, Dermatology Life Quality Index (DLQI), and Eczema Area and Severity Index (EASI) scores between the baseline visit and end-ofstudy visit for each cohort. The group receiving apremilast, 20 mg twice daily, displayed a significant reduction from baseline of pruritus (P=.02) and the DLQI (P=.003) at 3 months. The group receiving apremilast, 30 mg twice daily, displayed a significant reduction of the EASI (P=.008) and the DLQI (P=.01) at 3 months. At 6 months, there was a significant reduction of the EASI (P=.002), the visual analog scale (P=.03), and the DLQI (P=.03). Gene ontologic analyses comparing baseline with samples during treatment revealed alterations in immune response pathways, especially those related to cyclic adenosine monophosphate–mediated signaling. These results support further development of apremilast for treatment of atopic dermatitis. Larger randomized controlled studies are needed to more adequately evaluate both safety and efficacy. Limitations include the small sample size and absence of a control. clinicaltrials.gov Identifier: NCT01393158.

Tadalafil for the Treatment of Pulmonary Arterial Hypertension: A Double-Blind 52-Week Uncontrolled Extension Study

The aim of this study was to evaluate the long-term safety and durability of efficacy of tadalafil for pulmonary arterial hypertension. Tadalafil is an oral phosphodiesterase-5 inhibitor approved for PAH treatment. In the multicenter, placebo-controlled, randomized, 16-week PHIRST (Pulmonary Arterial Hypertension and Response to Tadalafil) study, tadalafil 40 mg improved exercise capacity and delayed clinical worsening. Eligible patients from PHIRST received once-daily tadalafil 20 mg (T20 mg) or 40 mg (T40 mg) (n = 357) in the double-blind, 52-week, uncontrolled extension study (PHIRST-2); 293 patients completed PHIRST-2. Durability of efficacy was explored using the 6-min walk distance (6MWD) test. Clinical worsening and changes in World Health Organization functional class were evaluated. The safety profile of tadalafil in PHIRST-2 was similar to that in PHIRST, with typical phosphodiesterase-5 inhibitor adverse events. The 6MWDs achieved in PHIRST for the subset of patients receiving T20 mg and T40 mg in both PHIRST and PHIRST-2 (406 ± 67 m [n = 52] and 413 ± 81 m [n = 59] at PHIRST-2 enrollment, respectively) were maintained at PHIRST-2 completion (415 ± 80 m [n = 51] and 410 ± 78 m [n = 59], respectively). Numerically fewer patients who were on T40 mg in PHIRST and PHIRST-2 experienced World Health Organization functional class deterioration (6% [n = 5]) compared with those randomized to T20 mg (9% [n = 7]) across both studies. Post hoc analyses showed that background bosentan use and higher 6MWD at PHIRST baseline were associated with fewer clinical worsening events. Long-term treatment with tadalafil was well tolerated in patients with pulmonary arterial hypertension. In patients receiving either T20 mg or T40 mg, the improvements in 6MWD demonstrated in the 16-week PHIRST study appeared sustained for up to 52 additional weeks of treatment in PHIRST-2. (Pulmonary Arterial Hypertension and Response to Tadalafil Study; NCT00549302).

A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis

A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis

Clinical Considerations for Roflumilast: A New Treatment for COPD

Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality and represents the fourth leading cause of death in the world. Roflumilast is the first oral phosphodiesterase inhibitor indicated to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and history of exacerbations. Roflumilast and its active metabolite have been associated with increased cyclic adenosine monophosphate (cyclic AMP) in the lungs and positive responses with inflammatory markers. Significant improvements in forced expiratory volume (1 sec) have been observed in clinical trials comparing roflumilast with placebo. Combination therapy of roflumilast (500 μg) with long-acting beta agonists resulted in reduced COPD exacerbations in patients with severe COPD. Adverse effects include weight loss, diarrhea, nausea, and psychiatric disturbances. Roflumilast may be associated with significant drug-drug interactions with CYP3A4 inducers (strong) and immunosuppressants. Roflumilast is a promising new agent in the treatment of COPD; however, additional studies comparing roflumilast with inhaled corticosteroids plus long-acting bronchodilators are needed.

Therapeutic Angiogenesis as a Potential Future Treatment Strategy for Erectile Dysfunction

The cavernous endothelium plays a crucial role in regulating the tone of the underlying smooth muscle and physiologic penile erection. Recently, the link between erectile dysfunction (ED) and cardiovascular disease was unveiled, and the main etiology of ED was found to be vasculogenic. Although oral phosphodiesterase-5 inhibitors are generally effective for men with ED, such therapies do not cure underlying vasculopathy in the corpus cavernosum tissue. This review addresses current preclinical protein, gene, and cell or stem cell therapies for enhancing cavernous endothelial regeneration and restoring erectile function.

Erectile dysfunction in hemodialysis: A systematic review

Men with chronic renal failure (CRF) on hemodialysis have been frequently associated with erectile dysfunction (ED), with an of between 20% to 87.7%. As a result of the multi-system disease processes present in many uremic men, it is apparent that the pathogenesis of ED is most probably multifactorial. Factors to be considered include peripheral vascular disease, neurogenic abnormalities, hormonal disturbances and medications used for treatment of conditions associated with CRF. These physiological abnormalities may be supplemented by significant psychological stresses and abnormalities resulting from chronic illness. Treatment must start with the determination and treatment of the underlying causes. In addition to psychological treatment, further lines of treatment of ED in CRF can be classified as 1st line (medical treatment which includes oral phosphodiesterase-5 inhibitors and hormone regulation), 2nd line (intracavernosal injection, vacuum constriction devices and alprostadil urethral suppositories) or 3rd line (surgical treatment). Renal transplantation improves the quality of life for some patients with CRF and subsequently it may improve erectile function in a significant number of them, however still there is high incidence of ED after transplantation.

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents, both autonomic and somatic, and supraspinal influences from visual, olfactory, and imaginary stimuli. Several central transmitters are involved in the erectile control. Dopamine, acetylcholine, nitric oxide (NO), and peptides, such as oxytocin and adrenocorticotropin/α-melanocyte-stimulating hormone, have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. The balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa (CC) and determines the functional state of the penis. Noradrenaline contracts both CC and penile vessels via stimulation of α₁-adrenoceptors. Neurogenic NO is considered the most important factor for relaxation of penile vessels and CC. The role of other mediators, released from nerves or endothelium, has not been definitely established. Erectile dysfunction (ED), defined as the "inability to achieve or maintain an erection adequate for sexual satisfaction," may have multiple causes and can be classified as psychogenic, vasculogenic or organic, neurologic, and endocrinologic. Many patients with ED respond well to the pharmacological treatments that are currently available, but there are still groups of patients in whom the response is unsatisfactory. The drugs used are able to substitute, partially or completely, the malfunctioning endogenous mechanisms that control penile erection. Most drugs have a direct action on penile tissue facilitating penile smooth muscle relaxation, including oral phosphodiesterase inhibitors and intracavernosal injections of prostaglandin E₁. Irrespective of the underlying cause, these drugs are effective in the majority of cases. Drugs with a central site of action have so far not been very successful. There is a need for therapeutic alternatives. This requires identification of new therapeutic targets and design of new approaches. Research in the field is expanding, and several promising new targets for future drugs have been identified.

Emerging concepts in erectile preservation following radical prostatectomy: a guide for clinicians

Radical prostatectomy (RP) is a commonly performed procedure for the management of prostate cancer. While documented oncologic outcome for early stage disease is excellent, functional impairments such as incontinence and erectile dysfunction (ED) are common after the procedure. Recent evidence has implicated cavernous nerve damage and subsequent corporal oxygen deprivation, as well as corporal inflammation, in the pathogenesis of post-RP ED. Targeted therapies such as oral phosphodiesterase-5 inhibitors, mechanical vacuum erection devices, local alprostadil delivery and testosterone replacement (for hypogonal patients) have demonstrated some efficacy in the management of post-RP ED. This review aggregates much of the recent data in support of these therapies and critically reviews them. The article then presents tools to assess patients and partner sexual function to aid in identifying and monitoring post-RP ED. Finally, the article describes a protocol in use at Baylor College of Medicine as a guide toward the development of a protocol for erectile preservation (EP). The purpose of this work is to educate clinicians on emerging concepts in EP and provide an implementable protocol for use in practice.

Pulmonary Vasodilation in Acute and Chronic Heart Failure: Empiricism and Evidence

Pulmonary hypertension in heart failure is associated with exercise intolerance and adverse outcomes. With the availability of multiple drugs that cause pulmonary vasodilation and decrease pulmonary arterial pressure, pulmonary hypertension becomes an attractive therapeutic target. Out of several classes of medications, oral phosphodiesterase inhibitors emerge as the most promising in terms of symptomatic improvement, hemodynamic benefits, reverse cardiac remodeling, and functional capacity. Future trials will show whether the use of these drugs translates to decreased morbidity and mortality in heart failure.

Combination therapy for erectile dysfunction: an update review

The introduction of oral phosphodiesterase-5 inhibitors (PDE5Is) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE5Is are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE5I monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE5I therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE5I plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, α-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

1818 CONTEMPORARY ROLE OF NOCTURAL PENILE TUMESCENCE RECORDING TO IDENTIFY ERECTILE DYSFUNCTION ETIOLOGY FOR SELECT CASES IN YOUNG MEN

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Peyronie's Disease/Surgical Therapy1 Apr 20111818 CONTEMPORARY ROLE OF NOCTURAL PENILE TUMESCENCE RECORDING TO IDENTIFY ERECTILE DYSFUNCTION ETIOLOGY FOR SELECT CASES IN YOUNG MEN Rany Shamloul, Anthony J. Bella, and Michael Adams Rany ShamloulRany Shamloul Ottawa, Canada More articles by this author , Anthony J. BellaAnthony J. Bella Ottawa, Canada More articles by this author , and Michael AdamsMichael Adams Kingston, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2190AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Identification of erectile dysfunction (ED) etiology in young men may present a challenge. Historically, nocturnal penile tumescence recording (NPTR) was used to differentiate psychogenic from organic ED but has also been criticized for being costly, complicated, and with poor reproducibility. We aim to evaluate the role, if any, of NPTR in the diagnosis of ED in young men. METHODS 25 less than 40 yr old (otherwise healthy) men with no known psychological diagnoses complaining of ED for at least 6 months were included in the study. Hormonal workup was negative. All failed multiple trials of 3 oral phosphodiesterase inhibitors. Color penile duplex ultrasound (CDU) (0.5cc trimix with 30 mg papaverine+10 μg PGE1+ 1 mg phentolamine/cc) did not produce rigid penetration (but was bedroom quality) and revealed degress of veno-occlusive dysfunction. In-home NPTR was recorded over 2 consecutive nights using the Rigiscan® (Timm Medical Technologies, MN). Presence of 3-6 erectile sessions over an 8-hour sleep, with each session lasting at least 10 min and yielding a penile radial rigidity greater than 70% at the tip of the penis was considered normal erectile activity. RESULTS No technical difficulties were reported for at-home testing. 18 (72%) of men had abnormal test results. However, 7 (28%) out of 25 men had completely normal erectile sessions during NPTR; in these men a diagnosis of psychogenic ED seems highly possible. CONCLUSIONS The select use of NPTR during evaluation of erectile function in young men can help identify difficult to diagnose cases of primarily psychogenic ED. We do not recommend routine use of NPTR for ED work-up, and limit use to cases where CDU is inconclusive. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e729 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rany Shamloul Ottawa, Canada More articles by this author Anthony J. Bella Ottawa, Canada More articles by this author Michael Adams Kingston, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

OBJECTIVEPatients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals.RESEARCH DESIGN AND METHODSFour groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test.RESULTSLocal delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin.CONCLUSIONSThese findings support the concept of cavernous endothelial regeneration by use of the recombinant Ang1 protein as a curative therapy for diabetic erectile dysfunction.

An update on new oral PDE5 inhibitors for the treatment of erectile dysfunction

The management of erectile dysfunction (ED) has been revolutionized by the discovery of phosphodiesterase 5 (PDE5) inhibitors, which have been commercially available for more than a decade and are the first-line therapeutic option for men with ED. Sildenafil, vardenafil and tadalafil were approved by the European Medicine Agency and the US FDA for the treatment of ED on the back of their high efficacy rates and favorable safety profiles. However, despite the fact that more than 50 million patients with ED worldwide have been successfully treated with one of these PDE5 inhibitors, some men--most notably those with severe neurologic damage, diabetes mellitus or severe vascular disease--are resistant to the currently available drugs and require more-invasive treatments, such as intracavernosal injection therapy. Partly as a consequence of this, research into alternative therapeutic approaches continues, including the development of new PDE5 inhibitors, centrally acting pharmaceutical agents, and application of molecular technologies such as gene therapy and stem cell therapy.

Intranasal Theophylline: A Novel Method to Treat Patients with Smell Loss (Hyposmia)

While the oral phosphodiesterase (PDE) inhibitor theophylline has proven useful in the treatment of hyposmia its efficacy has been limited by its side effects, its slow action to improve olfactory function requiring months of drug use and by development of drug resistance. To overcome these adverse effects an open label, single source clinical trial using intranasal theophylline was performed in 10 patients with hyposmia before and after both oral and intranasal theophylline. Intranasal theophylline was administered daily in each naris at a dose of 20μg of buffered drug through use of a clinically adapted syringe which delivered the drug into the mid‐upper nose. Patients were studied weekly for two weeks and then biweekly for four weeks. Both subjective and objective measurements of smell and taste function were obtained. After one week of intranasal drug eight of the 10 patients reported subjective improvement in both taste and smell function and appetite. Objective measurements with smell and taste function tests also improved in each of these patients. This improvement continued over the subsequent three weeks of the study. No side effects were experienced by any patient. Blood theophylline levels at the time of maximal smell and taste improvement were 0. After one week of discontinuing the intranasal drug two patients reported subjective diminution in smell function confirmed by objective smell and taste measurements whereas six patients maintained improvement for two months after intranasal theophylline was discontinued. This open label clinical trial suggests that intranasal theophylline is both safe and more effective than oral theophylline in the treatment of hyposmia.

Oral Phosphodiesterase-5 Inhibitors and Hormonal Treatments for Erectile Dysfunction: A Systematic Review and Meta-analysis

Oral Phosphodiesterase-5 Inhibitors and Hormonal Treatments for Erectile Dysfunction: A Systematic Review and Meta-analysis

Predictors of Recovery of Erectile Function after Unilateral Cavernous Nerve Graft Reconstruction at Radical Retropubic Prostatectomy

Although studies have reported a benefit to bilateral cavernous nerve graft (NG) interposition, the role of unilateral NG interposition in recovery of erectile function (EF) after radical prostatectomy (RP) with unilateral neurovascular bundle (NVB) resection is more controversial. To determine the probability and predictors of EF recovery after unilateral cavernous NG at RP with unilateral NVB resection. We retrospectively reviewed the records of preoperatively potent men who underwent RP with unilateral NVB resection and ipsilateral NG without prior radiation or hormonal therapy from 1999 to 2007. Postoperative EF was defined in two ways: (i) physician interview-based assessment (level 3: erections sometimes sufficient for intercourse; level 2: erections routinely sufficient for intercourse; level 1: normal erections; all with or without oral phosphodiesterase-5 inhibitor use); and (ii) according to the sum Q3 + Q4 on the International Index of Erectile Function (IIEF) questionnaire. EF recovery based on physician interview-based scale and IIEF questionnaire. In all, 131 men underwent unilateral NG. Median follow-up was 37.3 months. The 5-year actuarial probability of EF recovery was 46, 30, and 12% for levels 3, 2, and 1, respectively, and 40, 34, and 22% for IIEF Q3 + Q4 sum > or =6, > or =8, and = 10, respectively. On multivariate analysis, patient age, specimen weight, and plastic surgeon were predictive of EF recovery based on physician-interview whereas patient age, ethnicity, and plastic surgeon were predictive of EF recovery based on the IIEF questionnaire. The impact of plastic surgeon on EF recovery with unilateral NG would suggest that technical factors play a role in EF recovery after unilateral NG. Meticulous surgical technique with proper identification of proximal and distal recipient nerve endings may improve the chance of EF recovery. The variation in recovery rate among plastic surgeons would imply that there is a benefit to unilateral NG in EF recovery.

Oral Phosphodiesterase-5 Inhibitors and Hormonal Treatments for Erectile Dysfunction: A Systematic Review and Meta-analysis

Background: Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain. Purpose: To evaluate the efficacy and harms of oral phosphodiesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED. Data Sources: English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned. Study Selection: Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED. Data Extraction: Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities. Data Synthesis: Data, primarily from short-term trials (≤12 weeks), indicate that PDE-5 inhibitors were more effective than placebo in improving sexual intercourse success (69.0% vs. 35.0%). The proportion of men with improved erections was significantly greater among those treated with PDE-5 inhibitors (range, 67.0% to 89.0%) than with placebo (range, 27.0% to 35.0%). The PDE-5 inhibitors were associated with increased risk for any adverse events compared with placebo (for example, relative risk with sildenafil, 1.72 [95% CI, 1.53 to 1.93]). In 4 head-to-head RCTs comparing sildenafil, vardenafil, and tadalafil, improvement of ED and adverse events did not differ among treatments. Results from 15 RCTs evaluating hormonal treatment of ED were inconsistent on whether treatment improved outcomes. Evidence was insufficient regarding whether men with ED had a higher prevalence of hypogonadism than men without ED. Limitations: Many RCTs were of low methodological and reporting quality, particularly those involving hormonal treatments or directly comparing different PDE-5 inhibitors. Most RCTs provided only short-term efficacy and harms data. Conclusion: Oral PDE-5 inhibitors improved erectile functioning and had similar efficacy and safety profiles. Results on the efficacy of hormonal treatments and the value of hormone testing in men with ED were inconclusive. Primary Funding Source: Agency for Healthcare Research and Quality.

Oral Phosphodiesterase-5 Inhibitors and Hormonal Treatments for Erectile Dysfunction: A Systematic Review and Meta-analysis

Erectile dysfunction (ED) is a common male sexual disorder. The relative benefits and harms of pharmacologic therapies for ED, as well as the value of hormonal testing in men with ED, are uncertain. To evaluate the efficacy and harms of oral phosphodiesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED. English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned. Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED. Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities. Data, primarily from short-term trials (<or=12 weeks), indicate that PDE-5 inhibitors were more effective than placebo in improving sexual intercourse success (69.0% vs. 35.0%). The proportion of men with improved erections was significantly greater among those treated with PDE-5 inhibitors (range, 67.0% to 89.0%) than with placebo (range, 27.0% to 35.0%). The PDE-5 inhibitors were associated with increased risk for any adverse events compared with placebo (for example, relative risk with sildenafil, 1.72 [95% CI, 1.53 to 1.93]). In 4 head-to-head RCTs comparing sildenafil, vardenafil, and tadalafil, improvement of ED and adverse events did not differ among treatments. Results from 15 RCTs evaluating hormonal treatment of ED were inconsistent on whether treatment improved outcomes. Evidence was insufficient regarding whether men with ED had a higher prevalence of hypogonadism than men without ED. Many RCTs were of low methodological and reporting quality, particularly those involving hormonal treatments or directly comparing different PDE-5 inhibitors. Most RCTs provided only short-term efficacy and harms data. Oral PDE-5 inhibitors improved erectile functioning and had similar efficacy and safety profiles. Results on the efficacy of hormonal treatments and the value of hormone testing in men with ED were inconclusive. Agency for Healthcare Research and Quality.

Treatment of erectile dysfunction following spinal cord injury

Spinal cord injury (SCI) has a significant impact on erectile dysfunction. Treatment modalities for individuals with SCI are similar to treatments for those without SCI. Some of the most common methods of management include penile implants, oral phosphodiesterase (PDE) inhibitors, vacuum devices, intraurethral prostaglandins, and intracavernous injections. In addition to the advantages and disadvantages of these various modalities for able-bodied men, there are special considerations for men with SCI. Penile implants may help to keep an external condom catheter in place and provide more penile stability for intermittent catheterization. However, they have an increased risk of infection. Semirigid rods have an increased risk of erosion. Although convenient to use, PDE inhibitors are usually not effective in lower motor injuries. The hypotensive effects of intraurethral prostaglandins and PDE inhibitors need to be considered in SCI men with injuries at or above T6. Intracavernous injections are very effective; however, men with SCI require much lower doses than able-bodied men.

Patient preference and satisfaction in erectile dysfunction therapy: a comparison of the three phosphodiesterase-5 inhibitors sildenafil, vardenafil and tadalafil.

Erectile dysfunction (ED) is a problem that may affect up to 52% of men between the ages of 40 and 70. It can be distressing because of its negative effect on self-esteem, quality of life, and interpersonal relationships. Oral phosphodiesterase-5 inhibitors (PDE5 inhibitors) are now the first choice of treatment in ED. The availability of three (sildenafil citrate, tadalafil, and vardenafil) well tolerated and effective oral PDE5 inhibitors gives treatment options for men with ED. Although the mechanism of action is the same for the three drugs, they differ in their pharmacokinetics. Several preference studies were conducted between the three PDE5 inhibitors but they were not free from bias. Because of the lack of overwhelming reliable data showing that one PDE5 inhibitor is superior to another, current opinion is that the individual patient should have the opportunity to test all three drugs and then select the one that best suits him and his partner.