Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

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Previous ED Research: 2002-2006   
The Erectile Dysfunction File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Erectile Dysfunction, click HERE.

     
Latest Research on
Erectile Dysfunction
     
Am J Med. 2008 Jul;121(7):592-6. Epub 2008 Jun 4.
Regular intercourse protects against erectile dysfunction: Tampere Aging Male Urologic Study.
Koskimäki J, Shiri R, Tammela T, Häkkinen J, Hakama M, Auvinen A.
Tampere University Hospital, Department of Urology, Tampere, Finland. juha.koskimaki@sarment.fi

BACKGROUND: Erectile dysfunction is common among men aged more than 60 years. Its cause involves both physiologic and psychosocial factors. METHODS: To evaluate the effects of coital frequency on subsequent risk of erectile dysfunction, data were analyzed from a population-based 5-year follow-up study that was conducted in Pirkanmaa, Finland, using postal questionnaires. Assessment was based on the 5-item version of the validated International Index of Erectile Function. Men with erectile dysfunction at entry were excluded from the analysis. The study sample consisted of 989 men aged 55 to 75 years (mean 59.2 years). The most common comorbidities were hypertension (32%), heart disease (12%), depression (7%), diabetes (4%,) and cerebrovascular disorder (4%). RESULTS: The overall incidence of moderate or complete erectile dysfunction was 32 cases per 1000 person-years (95% confidence interval [CI], 27-38). After adjustment for comorbidity and other major risk factors, men reporting intercourse less than once per week at baseline had twice the incidence of erectile dysfunction compared with those reporting intercourse once per week (79 vs 33/1000, incidence rate ratio 2.2, 95% CI, 1.3-3.8). The risk of erectile dysfunction was inversely related to the frequency of intercourse. No relationship between morning erections and incidence of moderate or severe erectile dysfunction was found. CONCLUSION: Regular intercourse protects against the development of erectile dysfunction among men aged 55 to 75 years. This may have an impact on general health and quality of life; therefore, doctors should support patients' sexual activity.

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Curr Med Res Opin. 2008 Jul;24(7):1861-8. Epub 2008 May 27.
Integrating evidence from multiple sources to evaluate post-approval safety: an example of sildenafil citrate and cardiovascular events.
Sobel RE, Reynolds RF.
Epidemiology, Safety and Risk Management, Pfizer Inc, New York, NY 10017, USA. Rachel.Sobel@pfizer.com

OBJECTIVE: Recent high-profile medicine withdrawals have highlighted the complex decision-making process that regulators, pharmaceutical companies, prescribers, and patients must undertake in determining whether a drug has an appropriate benefit-risk balance. Our objective was to analyze the utility of different drug safety data sources and methods, using the experience of sildenafil citrate (Viagra) and post-approval concerns about its potential association with cardiovascular (CV) events (i.e., myocardial infarction [MI] and death) as a case study. METHODS: We evaluated safety data from three sources: the standard passive surveillance system (i.e., spontaneous reports filed to Pfizer Inc), pooled clinical trial data, and a prospective observational cohort study, the International Men's Health Study (IMHS). RESULTS: More than 28 000 spontaneous reports were received in the first 7 years after approval. Between 2001 and 2005, the proportion filed by persons other than healthcare professionals (61%) was approximately double the proportion averaged across five other drugs from the manufacturer's safety database. CV events and/or deaths represented 22.0% of reports, and 23% of reported deaths were medically unconfirmed reports made by persons other than healthcare professionals. In contrast, MI and all-cause mortality rates for sildenafil from both the pooled clinical trial data and the IMHS were similar to placebo, despite differences in methods and populations. CONCLUSIONS: These results suggest that passive surveillance may generate apparent signals of risk, as was the case with sildenafil and CV events. However, to adequately assess the benefit-risk profile of a drug, these signals must be evaluated via other data sources such as clinical trial and epidemiologic studies, as the apparent signal was not supported by more rigorously collected data. Our post-marketing analysis was unable to examine all potential influences of spontaneous reports, and the study data sources (although large for erectile dysfunction studies) were not designed to exclude small CV risks.

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Med J Aust. 2008 Jun 2;188(11):662-6.
Premature ejaculation: a clinical update.
Palmer NR, Stuckey BG.
Keogh Institute for Medical Research, Sir Charles Gairdner Hospital, Perth, WA, Australia.

Premature ejaculation (PE) is ejaculation occurring without control, on or shortly after vaginal penetration and before the subject wishes it, causing marked distress or interpersonal difficulties. PE is the most common male sexual complaint. Primary (lifelong) PE has a physiological basis. Therapy should involve the man and his partner. The primary aims of therapy are for the man to regain a sense of control over his ejaculation time and for him and his partner to feel satisfaction with sexual intercourse. The most effective therapies for primary PE are certain selective serotonin reuptake inhibitors, given on a daily basis or "on demand" before sexual activity. Topical anaesthetics have also been shown to be effective. The most common cause of secondary PE is declining erectile function. The approach to treating secondary PE is to treat the underlying condition.

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Aging Male. 2008 Jun;11(2):57-61.
Beneficial effects of testosterone administration on symptoms of the lower urinary tract in men with late-onset hypogonadism: a pilot study.
Kalinchenko S, Vishnevskiy EL, Koval AN, Mskhalaya GJ, Saad F.
Russian Research Center for Endocrinology, Moscow, Russia. Kalinchenko@list.ru

INTRODUCTION: Elderly men are bothered by lower urinary tract complaints designated as lower urinary tract symptoms (LUTS). In epidemiological studies LUTS appears strongly associated with erectile dysfunction, and also with metabolic syndrome. LUTS occurs at an age at which plasma testosterone levels decline, in some men to hypogonadal values. Objectives. This pilot study tested whether testosterone administration to elderly men complaining of LUTS and whose plasma testosterone levels are below normal, might alleviate LUTS. METHODS: Group 1 (n = 10) received treatment with testosterone gel (50 mg) daily for three months; group 2 (n = 20) received treatment with injections of testosterone undecanoate 1000 mg for 26 weeks. RESULTS: Upon these interventions, plasma testosterone increased to the normal range. Symptoms of LUTS, measured by the International Prostate Symptoms Score, improved significantly, and also scores of the Aging Males' Symptoms scale and international index of erectile function improved. There were no untoward effects on the prostate over this period of time of the study. CONCLUSION: Testosterone administration improved symptoms of LUTS in men with late-onset hypogonadism. The mechanism of action is as yet not understood, but it may be connected with or parallel with the effects of testosterone on penile tissues in hypogonadal men, such as on nitric oxide and phosphodiesterase.

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Curr Diabetes Rev. 2008 Feb;4(1):24-30.
Redefining the role of long-acting phosphodiesterase inhibitor tadalafil in the treatment of diabetic erectile dysfunction.
Bruzziches R, Greco EA, Pili M, Francomano D, Spera G, Aversa A.
Dip. to Fisiopatologia Medica, Room 37, Viale Policlinico 155, 00161 Rome, Italy; antonio.aversa@uniroma1.it.

Diabetes mellitus (DM) is an established risk factor predisposing to male erectile dysfunction (ED), and it has been calculated that more than 50% of diabetic men develop ED within ten years of diagnosis. It has been suggested that the risk of ED increases with metabolic indices of inadequate diabetes control and with a longer duration of disease. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the pathogenesis of diabetic ED. Coronary and peripheral atherosclerosis are frequent complications of DM and diabetic patients have an increased risk of future cardiovascular events comparable to that of patients with coronary artery disease. The prolonged half-life of tadalafil (17.5 hours) and its prolonged period of responsiveness (36-hours), constitute an ideal pharmacokinetic profile for once-a-day dosing and makes it an ideal candidate for rehabilitative therapy in DM patients, whereas a poor compliance with on-demand schedule is reported. The aim of this review will be to give an update on clinical overall efficacy and safety of tadalafil trials, i.e. in diabetic population, and finally provide evidences for redefining the role of chronic treatment in selected group of patients.

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Drugs. 2008;68(2):231-50.
Looking to the future for erectile dysfunction therapies.
Hatzimouratidis K, Hatzichristou DG.
Center for Sexual and Reproductive Health, Aristotle University of Thessaloniki, Thessaloniki, Greece.

The treatment of erectile dysfunction (ED) has been revolutionized during the last 2 decades with several treatment options now available. Most of these treatments are associated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice treatment option for ED by most physicians and patients. In addition, several new PDE5 inhibitors are candidates to enter the market in forthcoming years (avanafil, udenafil, SLx-2101, mirodenafil [SK3530]). However, obvious pharmacokinetic differences that result in a faster time-to-onset, longer half-life time and better safety profile are required for these drugs to be considered a truly better option for patients. Other molecules in development include selective dopamine, glutamate, serotonin and melanocortin receptor agonists, guanylate cyclase activators, rho-kinase inhibitors and hexarelin analogues, while the first trials on gene therapy and tissue engineering for reconstruction of corporal tissue are under way. Patients must be aware of all treatment options since no ideal treatment exists. It is expected that the availability of drugs with different mechanisms of action will allow physicians to offer more personalized medicine to their patients in the future. The development and adaptation of a patient-centred care model in sexual medicine will increase the efficacy and safety of current and future treatments.

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Drugs. 2008;68(2):209-29.
Guide to drug therapy for lower urinary tract symptoms in patients with benign prostatic obstruction : implications for sexual dysfunction.
Gur S, Kadowitz PJ, Hellstrom WJ.
Department of Urology, Tulane Health Sciences Center, New Orleans, Louisiana, USA.

The relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) caused by benign prostatic obstruction (BPO) has recently gained increasing attention. Both BPO and ED are highly prevalent in older men and both conditions frequently contribute to a reduction in overall quality of life. Current medical treatment of LUTS/BPO consists of monotherapy with alpha(1)-adrenoceptor antagonists or 5alpha-reductase inhibitors, a combination of these two agents or, in some cases, various phytotherapeutic approaches. When choosing a drug therapy, it is important to recognize that while 5alpha-reductase inhibitors increase the risk of ED and ejaculatory disorders, and combined therapy carries the cumulative risk of causing sexual dysfunction, some alpha(1)-adrenergic receptor antagonists have been reported to improve overall sexual function. Therefore, the successful evaluation and management of older men with LUTS associated with BPO should include an assessment of baseline sexual function and subsequent monitoring of medication-induced sexual adverse effects. In this review, we detail the pathophysiological mechanisms involved in LUTS/BPO-associated ED, including reduced nitric oxide/cyclic guanosine monophosphate system activity, enhanced endothelin-1/rhoA/rho kinase pathway activity, sympathetic overactivity, pelvic organ atherosclerosis and potential preventive approaches.

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BJU Int. 2008 Jan 10 [Epub ahead of print]
Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence.
Mathers MJ, Klotz T, Brandt AS, Roth S, Sommer F.
Urological Ambulatory Remscheid, Remsheid, Germany.

OBJECTIVE To test the hypothesis that a variable dosage of the oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil (25, 50, 100 mg) or vardenafil (5, 10, 25 mg) determined according to results obtained from nocturnal penile tumescence and rigidity (NPTR, RigiScan), given nightly for 1 year, can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED); this regimen was compared with a fixed daily dosage of sildenafil 25 mg or vardenafil 5 mg. PATIENTS AND METHODS In a prospective open-label, parallel-group trial 154 men with ED were randomized either to fixed low-dose sildenafil 25 mg or vardenafil 5 mg (group 1) or to the lowest erectile dosage of sildenafil (25, 50 or 100 mg) or vardenafil (5, 10 or 20 mg) (group 2) provoking an erectile event as measured by NPTR nightly for 1 year. The EF domain of the International Index of Erectile Function (IIEF) was assessed before and 1 year after the beginning of treatment, and at 4 weeks after ending treatment. RESULTS After 1 year, 27 of 63 (64%) evaluable men in group 1 had an EF domain score in the normal range, vs 46 of 61 (75%) men in group 2. After the subsequent 4-week wash-out phase, both groups continued to have improved EF domain scores; 22 of 63 (35%) men in group 1 still had a score in the normal range, whereas 38 of 61 (62%) in group 2 had a normal score. The EF domain score in group 1 and 2 improved significantly after 1 year of treatment, from 13.6 to 18.9, and 15.1 to 23.9, respectively (P < 0.01). After the subsequent 4-week wash-out phase, men from both groups maintained this significant level of EF, at 17.1 and 22.4, respectively (P < 0.05). CONCLUSION Nightly PDE5-inhibitor treatment 1 year in a dosage determined by NPTR measurements results in better EF than giving a fixed dosage of sildenafil (25 mg) or vardenafil (5 mg). This improvement persisted for >4 weeks beyond the end of treatment. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

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J Urol. 2008 Jan 17 [Epub ahead of print]
Daily Vardenafil for 6 Months Has No Detrimental Effects on Semen Characteristics or Reproductive Hormones in Men With Normal Baseline Levels.
Jarvi K, Dula E, Drehobl M, Pryor J, Shapiro J, Seger M.
Mount Sinai Hospital (KJ), Toronto, Ontario, Canada.

PURPOSE: Phosphodiesterase type 5 inhibitors are the first choice therapy in the treatment of erectile dysfunction. Many men in their reproductive years are now using phosphodiesterase type 5 inhibitors. The purpose of this study was to determine the effects of 6 months of treatment with 20 mg vardenafil, compared with 100 mg sildenafil and placebo, on semen characteristics and reproductive hormones in men with and without erectile dysfunction. MATERIALS AND METHODS: This was a randomized, double-blind, placebo controlled, parallel group, multicenter study. A total of 200 men with or without erectile dysfunction, able to produce semen samples without erectile dysfunction therapy, 25 to 64 years old, were randomized to daily treatment with vardenafil, sildenafil or placebo for 6 months. The primary variable was the percentage of vardenafil treated individuals with a 50% or greater decrease in mean sperm concentration from baseline to 6-month last observation carried forward, compared with placebo treated individuals. RESULTS: The between group difference (vardenafil minus placebo) in the percentage of patients with 50% or greater decrease in sperm concentration (baseline to 6 months last observation carried forward) was 0.07% (95% CI, -8.53% to 8.39%). Vardenafil also had no clinically significant effects on any other semen parameters, or on levels of reproductive hormones, when compared with placebo. Similar data were observed with sildenafil. CONCLUSIONS: This study demonstrated that vardenafil had no adverse effects on sperm concentration, compared with sildenafil and placebo, when administered daily at the maximum recommended dose for 6 months. Specifically, use of vardenafil for 6 months does not impair sperm concentration, total sperm count per ejaculate, or sperm morphology and motility. Levels of reproductive hormones were also unaffected.

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JSLS. 2007 Oct-Dec;11(4):443-8.
Patient-reported validated functional outcome after extraperitoneal robotic-assisted nerve-sparing radical prostatectomy.
Madeb R, Golijanin D, Knopf J, Vicente I, Erturk E, Patel HR, Joseph JV.
Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA. ralph_madeb@urmc.rochester.edu

BACKGROUND AND OBJECTIVES: Erectile function after prostate surgery is an important criterion for patients when they are choosing a treatment modality for prostate cancer. Improved visualization, dexterity, and precision afforded by the da Vinci robot allow a precise dissection of the neurovascular bundles. We objectively assessed erectile function after robot-assisted extraperitoneal prostatectomy by using the SHIM (IIEF-5) validated questionnaire. METHODS: Between July 2003 and September 2004, 150 consecutive men underwent da Vinci robot-assisted extraperitoneal radical prostatectomy for clinically localized prostate cancer. The IIEF-5 questionnaire was used to assess postoperative potency in 67 patients who were at least 6 months postsurgery. Erectile function was classified as impotent (<11), moderate dysfunction (11 to 15), mild dysfunction (16 to 21), and potent (22 to 25). All patients used oral pharmacological assistance postprocedure. RESULTS: Sixty-seven patients were available to complete the IIEF-5 questionnaire 6 months to 1 year postprostatectomy. Twelve patients were excluded from the study who abstained from all sexual activity after surgery for emotional or social reasons. Of the 55 patients evaluated, 22 (40%) were impotent, 3 (5.5%) had moderate erectile dysfunction (ED), 12 (21.8%) had mild ED, and 18 (32.7%) were fully potent. The table compares IIEF-5 scores with nerve-sparing status. Of patients who had bilateral nerve sparing, 28/45 (62.2%) had mild or no ED within 6 to 12 months postsurgery, and all expressed satisfaction with their current sexual function or rate of improvement after robotic prostatectomy. CONCLUSION: Robot-assisted extraperitoneal prostatectomy provides comparable outcomes to those of open surgery with regards to erectile function. Assessment of the ultimate maximal erectile function will require continued analysis, as this is likely to further improve beyond 6 to 12 months.

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Psychopharmacol Bull. 2007;40(4):205-18.
Androgens and the aging male.
Seidman SN.
Department of Psychiatry at the College of Physicians and Surgeons, Columbia University.

In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in male hypothalamic-pituitary-gonadal (HPG) axis function: testosterone levels decline through both central (pituitary) and peripheral (testicular) mechanisms, and there is a loss of the circadian rhythm of testosterone secretion. The progressive decline in testosterone levels has been demonstrated in both cross-sectional and longitudinal studies, and overall at least 25% of men over age 70 meet laboratory criteria for hypogonadism (ie, testosterone deficiency). Such age-associated HPG hypofunctioning, which has been termed "andropause," is thought to be responsible for a variety of symptoms experienced by elderly men, including weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, sexual dysfunction (including erectile dysfunction and loss of libido), and depression. Although, it has been difficult to establish correlations between these symptoms and plasma testosterone levels, there is some evidence that testosterone replacement leads to symptom relief, particularly with respect to muscle strength, bone mineral density, and erectile dysfunction. There is little evidence of a link between the HPG axis hypofunctioning and depressive illness, and exogenous androgens have not been consistently shown to have antidepressant activity. This article reviews the relationship between androgens, depression, and sexual function in aging men.

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BJU Int. 2007 Dec;100(6):1313-6.
Assessment of comparative treatment satisfaction with sildenafil citrate and penile injection therapy in patients responding to both.
Mulhall JP, Simmons J.
Urology, Memorial Sloan Kettering Cancer Center & Weill Cornell Medical Center, New York, NY, USA. jpm2005@med.cornell.edu

OBJECTIVE: To survey patient satisfaction, using validated questionnaires, in a group of men with erectile dysfunction who had used and responded to both sildenafil citrate and intracavernosal injection (ICI) therapy. PATIENTS AND METHODS: In all, 300 patients on ICI therapy were mailed questionnaire packets containing a survey enquiring about the patients' medical history, and two sets of the International Index of Erectile Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) sexual function surveys. If patients were using sildenafil alternating with ICI they were asked to complete the IIEF and EDITS questionnaires for each therapy. To identify only patients who had an adequate response to each agent, a score of >/=22 on the EF domain of the IIEF for sildenafil and ICI was required for inclusion in the final analysis. RESULTS: In all, 178 packets were evaluable; 123 men (69%) responded to ICI but not sildenafil, and 11 (6%) responded only to sildenafil and not ICI, leaving 37 patients who responded to both; these patients comprised the study population. There was no difference in EF domain score of the IIEF between the treatments; EDITS scores were significantly higher for ICI therapy than for sildenafil (P < 0.001). CONCLUSIONS: In patients who alternate the use of sildenafil and ICI therapy, satisfaction appears to be higher with ICI, although the erectogenic performance is similar. This suggests that patient satisfaction does not depend solely on erection performance, and that patients might benefit from various treatment options.

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Curr Opin Endocrinol Diabetes Obes. 2007 Dec;14(6):482-7.
Obesity and infertility.
Pasquali R, Patton L, Gambineri A.
Division of Endocrinology, Department of Internal Medicine, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum of Bologna, Bologna, Italy.

PURPOSE OF REVIEW: To summarize major factors affecting fertility in obesity. RECENT FINDINGS: Fertility can be negatively affected by obesity. In women, early onset of obesity favours the development of menses irregularities, chronic oligo-anovulation and infertility in the adult age. Obesity in women can also increase risk of miscarriages and impair the outcomes of assisted reproductive technologies and pregnancy, when the body mass index exceeds 30 kg/m. The main factors implicated in the association may be insulin excess and insulin resistance. These adverse effects of obesity are specifically evident in polycystic ovary syndrome. In men, obesity is associated with low testosterone levels. In massively obese individuals, reduced spermatogenesis associated with severe hypotestosteronemia may favour infertility. Moreover, the frequency of erectile dysfunction increases with increasing body mass index. SUMMARY: Much more attention should be paid to the impact of obesity on fertility in both women and men. This appears to be particularly important for women before assisted reproductive technologies are used. Treatment of obesity may improve androgen imbalance and erectile dysfunction, the major causes of infertility in obese men.

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Int J Clin Pract. 2007 Nov 19; [Epub ahead of print]
Integrating partners into erectile dysfunction treatment: improving the sexual experience for the couple.
Dean J, Rubio-Aurioles E, McCabe M, Eardley I, Speakman M, Buvat J, de Tejada IS, Fisher W.
St Peter's Andrology Centre, London, UK.

Introduction: Erectile dysfunction (ED) is a common condition estimated to affect more than 150 million men worldwide. ED should be regarded as a shared sexual problem which has significant detrimental effects both on the men who experience this condition and on their partners. Evidence to support partner involvement in ED therapy: Evidence shows that the partner plays a key supportive role in the man's ED treatment and in successful long-term ED therapy. Including the partner in consultations may highlight discordant attitudes and communication problems between couple members which may indicate treatment acceptance or rejection, or realistic or unrealistic treatment expectations. Options for partner involvement in ED therapy: Most patients with ED consult their physician in the absence of their partner. Therefore, involving the partner in therapy can be challenging. Two options which physicians should consider are: encouraging the patient to bring the partner into the office and, often more realistically, seeking information about, and providing information to, the partner, via the patient. Objectives: The objective of these recommendations is to provide practical guidance on treating couples affected by ED, and suggest techniques that may be helpful in integrating the partner into the process of ED treatment.

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J Sex Med. 2007 Nov 14; [Epub ahead of print]
Association between Psychiatric Symptoms and Erectile Dysfunction.
Corona G, Ricca V, Bandini E, Mannucci E, Petrone L, Fisher AD, Lotti F, Balercia G, Faravelli C, Forti G, Maggi M.
Andrology Unit, Department of Clinical Physiopathology, maggiore-Bellaria Hospital, Bologna, Italy.

Introduction. Erectile dysfunction (ED) is often associated with a wide array of psychiatric symptoms, although few studies systematically address their specific association with ED determinants. Aim. The aim of this study is to explore the relationship between ED (as assessed by SIEDY Structured Interview, a 13-item tool which identifies and quantifies the contribution of organic, relational, and intrapsychic domains of ED) and different psychopathological symptoms (as assessed by the Middlesex Hospital Questionnaire, a self-reported test for the screening of mental disorders in a nonpsychiatric setting). Methods. A consecutive series of 1,388 (mean age 51 +/- 13 years) male patients with ED was studied. Main Outcome Measures. Several hormonal and biochemical parameters were investigated, along with SIEDY Interview and the Middlesex Hospital Questionnaire. Results. Psychiatric symptoms resulted differentially associated with SIEDY domains. Depressive and phobic-anxiety symptoms were associated with the relational domain, somatization with the organic one, while free-floating anxiety, obsessive-compulsive, and phobic symptoms were significantly related with higher intrapsychic SIEDY scores. In addition, relevant depressive symptomatology was associated with hypogonadism, the presence of low frequency of intercourse, hypoactive sexual desire (HSD), and conflictual relationships within the couple and the family. Patients with high free-floating anxiety symptoms were younger, and complained of an unsatisfactory work and a conflictual relationship within family. Conversely, subjects with higher phobic anxious symptoms displayed a more robust relational functioning. Similar results were observed in subjects with obsessive-compulsive symptoms, who also reported a lower prevalence of HSD. Finally, subjects with somatization symptoms showed the worst erectile function. Conclusions. The main value of this study is that it alters various clinicians' belief that many psychiatric symptoms can be found among ED patients. Systematic testing of patients with ED, through psychiatric questionnaires, is recommended to detect even slight or moderate psychopathological distresses, which specifically associate and exacerbate sexual disturbances.

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Curr Med Res Opin. 2007 Nov 7; [Epub ahead of print]
Phosphodiesterase type 5 inhibitor therapy: identifying and exploring what attributes matter more to clinicians and patients in the management of erectile dysfunction.
Axilrod AC.

BACKGROUND: Erectile dysfunction (ED) is increasingly being recognized as a sentinel marker of future subsequent cardiovascular disease (CVD). Predicted increases in the prevalence of ED are due to a combination of an aging population and the increasing presence of comorbid conditions (hypertension, dyslipidemia, and diabetes). The dichotomy of the situation is that ED is often associated with these comorbidities, potentially leading to greater CVD risk, and conversely, these comorbidities have also been shown to increase the risk of developing ED. The successful treatment of ED with phosphodiesterase type 5 (PDE5) inhibitor therapy, therefore, is of paramount importance because it not only plays a critical role in restoring erectile function, but also provides clinicians with the opportunity to mitigate existing cardiovascular comorbidities or prevent the occurrence of CVD in this patient population.METHODS: This review is based on an electronic literature search of databases, including MEDLINE/PubMed, with information selected for its relevance to PDE5 inhibitor therapy comprising efficacy (e.g., first-dose success) in men with ED with or without comorbidities, onset and duration of action at specific time points, and patient preference.RESULTS: The introduction of PDE5 inhibitors represented a major advance in the treatment of ED. In spite of the availability of these agents, a large percentage of men are still not being treated, in many cases because of their reluctance to seek medical help. Moreover, many men who start treatment with PDE5 inhibitors discontinue treatment. Reasons for discontinuation are many and complex, including lack of initial or first-time success. Although of major concern to both patients and clinicians, there remains limited published clinical data on this specific parameter in the pertinent patient population and from prospective, randomized clinical studies.CONCLUSION: Data from studies suggests that the available PDE5 inhibitor therapies are effective in treating men with ED, including those who have increased CVD risk and those who have clinically identified cardiovascular comorbidities such as hypertension, dyslipidemia, and/or diabetes. According to data from studies, the attributes of PDE5 inhibitor therapy that matter more to clinicians and patients and that hold influence over treatment compliance include effectiveness in patients with cardiovascular comorbidities, first-dose effectiveness or early success, rapid onset of action, reliability, and tolerability.

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Urol Clin North Am. 2007 Nov;34(4):535-47.
Updates in inflatable penile prostheses.
Henry GD, Wilson SK.
Regional Urology, Shreveport, LA, USA.

Throughout history, many attempts to correct erectile dysfunction (ED) have been recorded. For the last 35 years, intracavernosal inflatable prostheses have been used, and these devices have undergone almost constant enhancement. The three-piece inflatable penile prosthesis has the highest patient satisfaction rates and lowest mechanical revision rates of almost any medically implanted device.

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Urol Clin North Am. 2007 Nov;34(4):483-96.
Centrally acting mechanisms for the treatment of male sexual dysfunction.
Miner MM, Seftel AD.
Division of Biology and Medicine, Department of Family Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA.

The development of pharmacologic therapy for erectile dysfunction (ED) has been possible because of incremental growth in our understanding of the physiology of normal erections and the complex pathophysiology of ED. Although the oral phosphodiesterase type 5 (PDE5) inhibitors have provided safe, effective treatment of ED for some men, a large proportion of men who have ED do not respond to PDE5 inhibitors or become less responsive or less satisfied as the duration of therapy increases. Also, men who are receiving organic nitrates and nitrates, such as amyl nitrate, cannot take PDE5 inhibitors because of nitrate interactions. The current options for treatment beyond PDE5 inhibitors are invasive, unappealing to some patients, and sometimes ineffective. The search for other options by which ED can be treated has branched out and now encompasses centrally acting mechanisms that control erectile function. Drugs available in Europe include apomorphine. This article focuses on the mechanism of centrally acting agents and reviews clinical data on potential new centrally acting drugs for men who have ED.

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Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005540.
Interventions for sexual dysfunction following treatments for cancer.
Miles C, Candy B, Jones L, Williams R, Tookman A, King M.

BACKGROUND: The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life including sexual function in people with cancer. Sexual dysfunction (SD) is a potential long-term complication of cancer treatments. OBJECTIVES: Evaluate effectiveness of interventions for SD following treatments for cancer and their adverse effects. SEARCH STRATEGY: The Cochrane Pain, Palliative & Supportive Care Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, Dissertation Abstracts and NHS Research Register were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) were included that assessed the effectiveness of a treatment for SD. The trial population comprised of adults of either sex who at trial entry had developed SD as a consequence of cancer treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed trial quality. Meta-analysis was considered for trials with comparable key characteristics. MAIN RESULTS: Eleven RCTs with a total of 1743 participants were identified. The quality of the trials was poor. Ten trials explored interventions for SD in men following treatments for non-metastatic prostate cancer. One trial explored effectiveness in women of a lubricating vaginal cream following radiotherapy for cervical cancer.The strongest evidence (from four trials) was on oral phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) following radiotherapy of the prostate or radical prostatectomy. The results using validated measures in all trials significantly favoured those in the PDE5 inhibitor group(s). The combined results of two trials indicated a significantly greater improvement in ED in the PDE5 inhibitor groups (odds ratio (OR) 10.09 95% confidence interval (CI) 6.20 to 16.43). Negative effects were few and usually mild to moderate headaches or flushing. One trial reported more clinically serious events including six events of tachycardia and six of chest pain.Following prostate cancer treatments there was some evidence that PDE5 inhibitors are more effective in combination with acetyl-L-carnitine and propionyl-L-carnitine and that sexual counselling improves self-administration of prostaglandin intra-cavernous injection for SD. There was some evidence following treatment for prostate cancer that transurethral alprostadil and vacuum constriction devices reduce SD, although in both trials negative effects were fairly common. There is some evidence that vaginal lubricating creams reduce SD. AUTHORS' CONCLUSIONS: PDE5 inhibitors are an effective treatment for SD secondary to treatments for prostate cancer. Other interventions identified need to be tested in further RCTs. The SD interventions in this review are not representative of the range available for men and women. Further evaluations are needed for these interventions for SD following cancer treatments.

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Ned Tijdschr Geneeskd. 2007 Sep 22;151(38):2101-4.
[From the Cochrane Library: Phosphodiesterase inhibitors are effective in treating erectile dysfunction in diabetic men]
[Article in Dutch]
Hamerlynck JV, Middeldorp S, Hooft L.
Academisch Medisch Centrum/Universiteit van Amsterdam, Dutch Cochrane Centre, J1B-108, Postbus 22.660, 1100 DD Amsterdam. j.v.hamerlynck@amc.uva.nl

Erectile dysfunction is a common multifactorial complication of diabetes mellitus. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. A recent Cochrane systematic review assessed the effects ofPDE-5 inhibitors in patients with diabetes mellitus and erectile dysfunction from 8 randomized placebo-controlled trials (a total of 1759 participants). The duration of therapy was mainly 12 weeks. The weighted mean difference (WMD) for the International Index of Erectile Function (erectile dysfunction domain) at the end of the study period was 6.6 in favour of the PDE-5 inhibitors arm. The relative risk for answering 'yes' to a global efficacy question ('did the treatment improve your erections?') was 3.8 in the PDE-5 inhibitors arm compared with the control arm. Headache and flushing were the most common adverse events, followed by flu-like symptoms, dyspepsia, myalgia, vision disorders and lower back pain. The overall risk ratio for developing any adverse reaction was 4.8 in the PDE-5 inhibitors arm as compared to the control arm. It was concluded that sufficient evidence exists that treatment with PDE-5 inhibitors can improve erectile dysfunction in diabetic men.

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Rev Urol. 2007 Summer;9(3):99-105.
Oral and non-oral combination therapy for erectile dysfunction.
Nehra A.
Department of Urology, Mayo Clinic College of Medicine Rochester, MN.

An estimated 30 million men in the United States suffer from varying degrees of erectile dysfunction. Increasing age and comorbidities are likely to increase the number of men who are initially refractory or become refractory to phosphodiesterase (PDE)-5 inhibitors, the most popular oral therapy. Combination therapy, a concept well proved in other areas of medicine, is therefore of increasing importance. Combination oral and non-oral (intracavernosal injection and intraurethral application) therapies have been shown to salvage monotherapy. The early introduction of combination therapy has been shown to expedite both the return of natural function and PDE-5 inhibitor responsiveness in post-prostatectomy patients with no reports of serious adverse events. Larger controlled studies are needed to corroborate those encouraging findings.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004825.
Psychosocial interventions for erectile dysfunction.
Melnik T, Soares B, Nasselo A.

BACKGROUND: Normal sexual function is a biopsychosocial process and relies on the coordination of psychological, endocrine, vascular, and neurological factors. Recent data show that psychological factors are involved in a substantial number of cases of erectile dysfunction (ED) alone or in combination with organic causes. However, in contrast to the advances in somatic research of erectile dysfunction, scientific literature shows contradictory reports on the results of psychotherapy for the treatment of ED. OBJECTIVES: To evaluate the effectiveness of psychosocial interventions for the treatment of ED compared to oral drugs, local injection, vacuum devices and other psychosocial interventions, that may include any psycho-educative methods and psychotherapy, or both, of any kind. SEARCH STRATEGY: The following databases were searched to identify randomised or quasi-randomised controlled trials: MEDLINE (1966 to 2007), EMBASE (1980 to 2007), psycINFO (1974 to 2007), LILACS (1980 to 2007), DISSERTATION ABSTRACTS (2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2007). Besides this electronic search cross checking the references of all identified trials, contact with the first author of all included trials was performed in order to obtain data on other published or unpublished trials. Handsearch of the International Journal of Impotence Research and Journal of Sex and Marital Therapy since its first issue and contact with scientific societies for ED completed the search strategy. SELECTION CRITERIA: All relevant randomised and quasi-randomised controlled trials evaluating psychosocial interventions for ED. DATA COLLECTION AND ANALYSIS: Authors of the review independently selected trials found with the search strategy, extracted data, assessed trial quality, and analysed results. For categorical outcomes the pooled relative risks (RR) were calculated, and for continuous outcomes mean differences between interventions were calculated as well. Statistical heterogeneity was addressed. MAIN RESULTS: Nine randomised (Banner 2000; Baum 2000; Goldman 1990; Kilmann 1987; Kockott 1975; Melnik 2005; Munjack 1984; Price 1981; Wylie 2003) and two quasi-randomised trials (Ansari 1976; Van Der Windt 2002), involving 398 men with ED (141 in psychotherapy group, 109 received medication, 68 psychotherapy plus medication, 20 vacuum devices and 59 control group) met the inclusion criteria. In data pooled from five randomised trials (Kockott 1975; Ansari 1976; Price 1981; Munjack 1984; Kilmann 1987), group psychotherapy was more likely than the control group (waiting list - a group of participants who did not receive any active intervention) to reduce the number of men with "persistence of erectile dysfunction" at post-treatment (RR 0.40, 95% CI 0.17 to 0.98, N = 100; NNT 1.61, 95% CI 0.97 to 4.76).At six months follow up there was continued maintenance of reduction of men with "persistence of ED" in favour of group psychotherapy (RR 0.43, 95% CI 0.26 to 0.72, N = 37; NNT 1.58, 95% CI 1.17 to 2.43).In data pooled from two randomised trials (Price 1981; Kilmann 1987), sex-group psychotherapy reduced the number of men with "persistence of erectile dysfunction" in post-treatment (RR 0.13, 95% CI 0.04 to 0.43, N = 37), with a 95% response rate for sex therapy and 0% for the control group (waiting list - no treatment) (NNT 1.07, 95% CI 0.86 to 1.44).Treatment response appeared to vary between patient subgroups, although there was no significant difference in improvement in erectile function according to mean group age, type of relationship, and severity of ED. In two trials (Melnik 2005; Banner 2000) that compared group therapy plus sildenafil citrate versus sildenafil, men randomised to receive group therapy plus sildenafil showed significant reduction of "persistence of ED" (RR 0.46, 95% CI 0.24 to 0.88; NNT 3.57, 95% CI 2 to 16.7, N = 71), and were less likely than those receiving only sildenafil to drop out (RR 0.29, 95% CI 0.09 to 0.93).One small trial (Melnik 2005) directly compared group therapy and sildenafil citrate. It found a significant difference favouring group therapy versus sildenafil in the mean difference of the IIEF (WMD -12.40, 95% CI -20.81 to -3.99, N = 20).No differences in effectiveness were found between psychosocial interventions versus local injection and vacuum devices. AUTHORS' CONCLUSIONS: There was evidence that group psychotherapy may improve erectile function. Treatment response varied between patient subgroups, but focused sex-group therapy showed greater efficacy than control group (no treatment). In a meta-analysis that compared group therapy plus sildenafil citrate versus sildenafil, men randomised to receive group therapy plus sildenafil showed significant improvement of successful intercourse, and were less likely than those receiving only sildenafil to drop out. Group psychotherapy also significantly improved ED compared to sildenafil citrate alone. Regarding the effectiveness of psychosocial interventions for the treatment of ED compared to local injection, vacuum devices and other psychosocial techniques, no differences were found.

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J Sex Med. 2007 Jul;4(4 Pt 2):1117-25.
Integrated sildenafil and cognitive-behavior sex therapy for psychogenic erectile dysfunction: a pilot study.
Banner LL, Anderson RU.
Center for Sexual Health, San Jose, CA, USA.

Introduction. Men with psychogenic erectile dysfunction (ED) present a challenge to physicians. Treatment with pharmacological agents alone does not address the complexities of the causative or resulting psychological issues. Aim. To evaluate the effectiveness of an integrative treatment protocol (ITP) with sildenafil and cognitive-behavior sex therapy (CBST) compared with sildenafil alone for men with psychogenic ED. Main Outcome Measures. Change from baseline on the International Index of Erectile Function (IIEF) in the domains of erectile function and sexual satisfaction to demonstrate improved sexual functioning and confidence. Methods. Men with psychogenic ED and female partners were randomized to receive either sildenafil alone or an ITP with sildenafil and CBST for the first 4 weeks. In the last 4 weeks, couples in the sildenafil group added CBST sessions to their regimen; patients in the ITP group continued the combined therapy. The IIEF questionnaire was used to compare erectile function and overall satisfaction serially at pretreatment, 4, and 8 weeks. Couples who met the success criteria in both domains after the first 4 weeks received no further treatment. Results. Fifty-three couples constituted the study population. After the first 4 weeks of sildenafil and ITP, 48% of men met criteria for success on erectile function and 65.5% for satisfaction compared to men on sildenafil alone with 29% and 37.5% success rates, respectively. After the last 4 weeks, integration of CBST with sildenafil resulted in a 58% success rate for erectile function which was comparable to the 66% rate for the initial drug/ITP group; satisfaction rates for men were 45% and 75%, respectively. Conclusions. CBST was shown to have a positive influence when used throughout the entire 8 weeks of the ITP or added to the sildenafil in the last 4 weeks. Although patients in both treatment regimens had significant improvements in the IIEF domain scores confirming efficacy of sildenafil, those in the CBST and drug regimen achieved higher rates of clinical success within the first 4 weeks of therapy. Banner LL, and Anderson RU. Integrated sildenafil and cognitive-behavior sex therapy for psychogenic erectile dysfunction: A pilot study. J Sex Med 2007;4:1117-1125.

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Int J Impot Res. 2007 Jul 5; [Epub ahead of print]
Lower urinary tract symptoms and erectile dysfunction; links for diagnosis, management and treatment.
Ponholzer A, Madersbacher S.
1Department of Urology and Andrology, Donauspital, Vienna, Austria.

Recent large-scale epidemiological studies have documented a strong association between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). This observation has two important scientific and clinical aspects: (i) to reveal the pathomechanism linking LUTS and ED and (ii) to consider this fact in the individual approach for diagnosis and management of these two disorders. The following hypotheses are under investigation to explain the relation between LUTS and ED: (i) an increased Rho-kinase activation, (ii) an alpha-adrenergic receptor imbalance, (iii) a decrease of NOS/NO in the endothelium, (iv) atherosclerosis affecting the small pelvis and (v) an autonomic hyperactivity, each affecting simultaneously bladder, prostate and penis. According to a recent randomized trial, sildenafil has a positive effect on LUTS yet not on uroflowmetry in men with LUTS and ED. Although further trials are mandatory, phosphodiesterase-5 inhibitors might play a role in the management of LUTS in the future. alpha-Blockers have no relevant effect on erectile function, tamsulosin leads to retrograde ejaculation in up to 10%. 5alpha-Reductase inhibitors are associated with ED, loss of libido and reduction of ejaculate volume in up to 10%. Transurethral and open prostatectomy induce retrograde ejaculation in up to 90% of patients while their impact on erectile function is still controversially discussed. Minimal invasive treatment options (laser prostatectomy, transurethral microwave thermotherapy) have a lower rate of retrograde ejaculation in the range of 20-70%. LUTS and ED are strongly linked although the exact mechanism is poorly understood. Men seeking for help for LUTS/benign prostatic hyperplasia should be assessed for different aspects of sexual dysfunction and informed regarding the impact of medication and surgery on sexual health.International Journal of Impotence Research advance online publication, 5 July 2007; doi:10.1038/sj.ijir.3901578.

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Int J Impot Res. 2007 Jul 5; [Epub ahead of print]
Sildenafil reduces bother associated with erectile dysfunction: pooled analysis of five randomized, double-blind trials.
Seftel AD, Creanga DL, Levinson IP.
1Department of Urology, Case Western Reserve University, Cleveland, OH, USA.

Improvement in bother associated with erectile dysfunction (ED) is an important aspect of successful treatment of ED. Changes in erectile function and the bother associated with ED were assessed in this analysis of pooled data from five 12-week, multicenter, randomized, double-blind, placebo-controlled, flexible-dose studies of sildenafil. Men who received sildenafil (n=578, vs placebo, n=550) had significantly greater (least squares mean+/-s.e.) improvement in erectile function (EF) domain scores of the international index of erectile function (IIEF) (10.0+/-0.3 vs 1.0+/-0.3, P<0.0001) and in erection distress scale (EDS) total transformed score (18.8+/-0.8 vs 4.8+/-0.9, P<0.0001). Scores on individual questions of the EDS were 24-65% higher after treatment with sildenafil (vs 8-12%, for placebo). The change in EF domain score correlated positively with the change in total transformed EDS score (0.43, P<0.0001). Successful treatment of ED with sildenafil may reduce the bother associated with ED.International Journal of Impotence Research advance online publication, 5 July 2007; doi:10.1038/sj.ijir.3901579.

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Int J Clin Pract. 2007 Jul;61(7):1198-208.
Diagnosis and management of erectile dysfunction in the primary care setting.
Rosenberg MT.
Mid-Michigan Health Centers, Jackson, MI, USA.

Recent advances in the management of erectile dysfunction (ED) involve the use of oral phosphodiesterase type-5 (PDE-5) inhibitor therapies which have transformed the perception of ED for both the patient and the healthcare provider. Recent treatment guidelines, including the American Urological Association (AUA) 2005 guidelines, promote a goal-oriented approach to therapy and emphasise that PDE-5 therapy should be offered to patients with ED as a first-line treatment option, unless contraindicated. Evidence-based studies have identified an association between ED and the presence of risk factors for cardiovascular and other vascular diseases, implicating ED as a marker for other vascular conditions. Therefore, the importance of screening and diagnosis in the primary care setting is paramount in the diagnosis and management of ED-associated comorbidities. This review provides an update on ED screening and management focusing on the use of PDE-5 inhibitor therapy in the primary care setting and also discusses clinical efficacy parameters with regard to recent results from clinical trials.

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Curr Top Med Chem. 2007;7(12):1137-44.
Melanocortins in the treatment of male and female sexual dysfunction.
Shadiack AM, Sharma SD, Earle DC, Spana C, Hallam TJ.
Palatin Technologies, Inc., Cranbury, NJ, USA. ashadiack@palatin.com.

Melanocortinergic agents are currently being investigated for a possible therapeutic role in male and female sexual dysfunction. These investigations were sparked by findings that systemic administration of a synthetic analog of alpha-MSH, MT-II, causes penile erections in a variety of species, including humans. Several other melanocortinergic agents including HP-228, THIQ, and bremelanotide (PT-141) have since been shown to have erectogenic properties thought to be due to binding to melanocortin receptors in the central nervous system, particularly the hypothalamus. Bremelanotide, a nasally administered synthetic peptide, is the only melanocortinergic agent that has been clinically studied in both males and females. Data from Phase II clinical trials of bremelanotide support the use of melanocortin-based therapy for erectile dysfunction. Studies using animal models have demonstrated that pre-copulatory behaviors in female rats analogous to sexual arousal are evoked, and preliminary clinical data also suggest a role in promoting sexual desire and arousal in women. Based on bremelanotide clinical experience, administration of a melanocortin agonist is well tolerated and not associated the hypotension observed with phosphodiesterase-5 inhibitors currently used to treat erectile dysfunction. This review discusses investigations of melanocortin agonists for the treatment of sexual dysfunction with emphasis on proposed sites and mechanisms of action in the central nervous system that appear to be involved in melanocortinergic modulation of sexual function. Current research validates use of melanocortinergic agents for the treatment of both male and female sexual dysfunction.

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Int J Impot Res. 2007 Jun 21; [Epub ahead of print]
Testosterone therapy in women: its role in the management of hypoactive sexual desire disorder.
Abdallah RT, Simon JA.
1Department of Obsterics and Gynecology, George Washington University, Washington, DC, USA.

Disorders of sexual dysfunction occur in nearly half of women during their life, and hypoactive sexual desire disorder accounts for most of those complaints. Although the relationship between low endogenous testosterone levels and sexual desire disorders in women has not been empirically established, clinical trials have shown that exogenous testosterone therapy improves arousability, sexual desire and fantasy, frequency of sexual activity and orgasm, and satisfaction and pleasure from the sexual act. Its therapeutic role in bone mineral density, fatigue, well-being and hot flashes requires more study before specific recommendations can be made. Potential adverse effects of testosterone therapy include hirsutism, acne and deepening of the voice along with changes in lipid profiles. While less well understood, concern after increased risks for breast cancer and cardiovascular events has been raised about this therapy. Testosterone therapy is available in various formulations; the most commonly used are oral and transdermal, including patches, gels, creams and ointments.International Journal of Impotence Research advance online publication, 21 June 2007; doi:10.1038/sj.ijir.3901558.

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Cardiol Rev. 2007 Mar-Apr;15(2):76-86.
Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease.
Ravipati G, McClung JA, Aronow WS, Peterson SJ, Frishman WH.
Division of General Internal Medicine, New York Medical College/Westchester Medical Center, Valhalla, New York 10595, USA.

Since the discovery of sildenafil in 1989 as a highly selective inhibitor of the phosphodiesterase type-5 (PDE-5) receptor, 2 additional PDE-5 inhibitors, tadalafil and vardenafil, have emerged as safe and effective treatments of erectile dysfunction (ED). Enzymes in the PDE family catalyze the hydrolysis of the intracellular signaling molecules cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which is the second messenger of nitric oxide (NO) and a principal mediator of smooth muscle relaxation and vasodilation. Sildenafil was initially introduced for clinical use as the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Erection is largely a hemodynamic event, which is regulated by vascular tone and blood flow balance in the penis. Endothelial dysfunction, an early component of atherosclerosis, may inhibit a vascular event such as erection and is rarely confined to the arteries supplying blood to the penis, but more likely occurs throughout the vascular bed. In addition to the effects of the NO-cGMP signaling pathway on cavernosal smooth muscle, clinical findings have suggested that vascular tone in the pulmonary, coronary, and other vascular tissues expressed by PDE-5 is also influenced by this signal transduction mechanism. This has led to the emergence of novel therapeutic indications for sildenafil over a range of cardiovascular conditions that are either well-established risk factors or comorbidities with ED. Recently, the U.S. Food and Drug Administration approved sildenafil as an orally active therapy for the treatment of primary pulmonary hypertension. The drug will be marketed under the trade name of Revatio, not Viagra, the name used for the ED indication. The approved dose for primary pulmonary hypertension is 20 mg 3 times daily.

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J Urol. 2007 Mar;177(3):1071-7.
Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial.
McVary KT, Monnig W, Camps JL Jr, Young JM, Tseng LJ, van den Ende G.
Northwestern University Feinberg School of Medicine, Chicago, Illinois.

PURPOSE: We evaluated sildenafil for erectile dysfunction and lower urinary tract symptoms in men with the 2 conditions. MATERIALS AND METHODS: This was a 12-week, double-blind, placebo controlled study of sildenafil in men 45 years or older who scored 25 or less on the erectile function domain of the International Index of Erectile Function and 12 or greater on the International Prostate Symptom Score. Men with confirmed or suspected prostate malignancy, or prostate specific antigen 10 ng/ml or more were excluded. End points were changes in International Index of Erectile Function domain scores, International Prostate Symptom Score (irritative, obstructive and quality of life), the Benign Prostatic Hyperplasia Impact Index, the Self-Esteem And Relationship questionnaire and Erectile Dysfunction Inventory of Treatment Satisfaction Index Score. RESULTS: The 189 men receiving sildenafil had significant improvements in erectile function domain score vs the 180 on placebo (9.17 vs 1.86, p <0.0001) and on all other International Index of Erectile Function domains. In men on sildenafil vs placebo significant improvements were observed in International Prostate Symptom Score (-6.32 vs -1.93, p <0.0001), Benign Prostatic Hyperplasia Impact Index (-2.0 vs -0.9, p <0.0001), mean International Prostate Symptom Score quality of life score (-0.97 vs -0.29, p <0.0001) and total Self-Esteem And Relationship questionnaire scores (24.6 vs 4.3, p <0.0001). There was no difference in urinary flow between the groups (p = 0.08). Significantly more sildenafil vs placebo treated patients were satisfied with treatment (71.2 vs 41.7, p <0.0001). Sildenafil was well tolerated. CONCLUSIONS: Improved erectile dysfunction and lower urinary tract symptoms with sildenafil in men with the 2 conditions were associated with improved quality of life and treatment satisfaction. Daily dosing with sildenafil may improve lower urinary tract symptoms. However, the lack of effect on urinary flow rates may mean that a new basic pathophysiology paradigm is needed to explain the etiology of lower urinary tract symptoms.

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Int Urol Nephrol. 2007 Feb 20; [Epub ahead of print]
Sildenafil combined with continuous positive airway pressure for treatment of erectile dysfunction in men with obstructive sleep apnea.
Perimenis P, Konstantinopoulos A, Karkoulias K, Markou S, Perimeni P, Spyropoulos K.
Department of Urology, University of Patras, Rio, Patras, 26500, Greece, petperim@upatras.gr.

OBJECTIVES: To assess efficacy and safety of the combination of sildenafil and continuous positive airway pressure (CPAP), and satisfaction with treatment for erectile dysfunction (ED) in men with obstructive sleep apnea (OSA). PATIENTS AND METHODS: Forty men suffering from OSA and concurrent ED were treated with CPAP after a thorough investigation. After a 4-week run-in period, the patients were randomly allocated to treatment for 6 weeks; 20 men to the combination group, receiving additionally 100 mg sildenafil on demand for intercourse, and 20 men to CPAP alone. After a 1-week washout phase, the two groups switched to the other treatment arm for an additional 6 weeks period. End points for efficacy evaluation were the percentage of successful attempts for intercourse based on an event log and the overall satisfaction with sildenafil in the treatment of ED. RESULTS: The patients recorded a total of 149 attempts for intercourse during the run-in phase with a success rate of 19.5%. During the 12 weeks of treatment, the success rate of intercourse attempts was 24.8% when only on CPAP and 61.1% when in combination with sildenafil (P < 0.001). Of the studied men, 70% were satisfied with the use of sildenafil while 30% remained unhappy with this additional treatment. CONCLUSIONS: Sildenafil in combination with CPAP appears clearly superior to CPAP alone. The efficacy of this combination is superior to that of sildenafil alone, as reported in previous studies. Both treatment modalities are safe and well tolerated. However, approximately one-third of the patients remain unsatisfied even from the combination treatment. Further treatment options are needed.

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BJU Int. 2007 Feb 15; [Epub ahead of print]
Effects of testosterone on erectile function: implications for the therapy of erectile dysfunction.
Saad F, Grahl AS, Aversa A, Yassin AA, Kadioglu A, Moncada I, Eardley I.
Freelance (Medical Writer), Ulm, Germany.

Sexual potency declines with age, as does the efficiency of erection. Many studies show that different patterns of erectile dysfunction (ED), varying from occasional inability to obtain a full erection, impairment throughout intercourse and total absence of erectile response, might not be triggered by psychological factors only. Recent research indicates that ED relies on organic causes, and has challenged the development of new therapies. One therapeutic approach in patients who have testosterone deficiency is based on androgen therapy. Thus, we reviewed data on testosterone-induced effects relative to erectile function, summarizing the results from studies reported in 1991-2006 on testosterone therapy in patients with ED and hypogonadism, with a special focus on men not responding to phosphodiesterase-5 (PDE-5) inhibitors. We searched several computerized databases parallel with printed bibliographic references. Many studies have established animal models, which confirm that testosterone is important in modulating the central and peripheral regulation of ED. Testosterone deprivation has a strong negative impact on the structure of penile tissues and erectile nerves, which can be prevented by androgen administration. Combined therapy regimens with PDE-5 inhibitors and testosterone might improve ED in patients with hypogonadism of different causes. Thus, androgen treatment in hypogonadic patients, including those unresponsive to PDE-5 inhibitors, often results in an improvement of ED. Testosterone therapy is safe and convenient, while rapidly correcting low testosterone levels.

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BJOG. 2007 Jan 26; [Epub ahead of print]
Sexual function and satisfaction in heterosexual couples when men are administered sildenafil citrate (Viagra(R)) for erectile dysfunction: a multicentre, randomised, double-blind, placebo-controlled trial.
Heiman JR, Talley DR, Bailen JL, Oskin TA, Rosenberg SJ, Pace CR, Creanga DL, Bavendam T.
Kinsey Institute for Research in Sex, Gender and Reproduction, Indiana University, Bloomington, IN, USA.

Objective To investigate the effect of improvement in erectile dysfunction (ED) on sexual function and satisfaction measures in heterosexual couples in which the woman reports that sexual intercourse is unsatisfactory at least half of the time. Design Multicentre, double-blind, placebo-controlled study. Setting Outpatient medical clinics. Population Hundred and eighty men with ED and their female partners in whom sexual intercourse was satisfactory about half the time or less (score of </=3 on the Female Partner of ED Subject Questionnaire question 3 [FePEDS Q3]). Methods Men were randomised to flexible-dose sildenafil (25, 50, and 100 mg) or placebo as needed for 12 weeks. Main outcome measures Primary: FePEDS Q3 ('Over the past four weeks, when you had sexual intercourse, how often was it satisfactory for you?') scored as 0 (no sexual activity) and 1 (almost never or never) to 5 (almost always or always). Secondary, partners: Sexual Function Questionnaire, Female Sexual Function Index (FSFI), and ED Inventory of Treatment Satisfaction (EDITS) partner version (EDITS-Partner). Secondary, men: International Index of Erectile Function (IIEF), General Efficacy Questions, event log data, Self-Esteem And Relationship questionnaire, and EDITS. Secondary, partners and men: Dyadic Adjustment Scale. Results The intention-to-treat population included 85 sildenafil recipients (mean age 59 +/- 12 years) and 91 placebo recipients (mean age 57 +/- 11 years). Most partners (aged 20-79 years; mean, 54 years) were postmenopausal. Sildenafil compared with placebo couples had greater improvement in the primary outcome (FePEDS Q3 [P < 0.0001]) and in sexual function, intercourse success rates, and secondary sexual satisfaction measures (FSFI satisfaction domain [P < 0.0001] and IIEF satisfaction domains [P < 0.001]) and had higher treatment satisfaction (EDITS and EDITS-Partner; P < 0.0001). Several predictors of improvement were identified, and improvement in one member of the couple correlated positively with improvement in the other member. Conclusions The interdependence of sexual function and sexual satisfaction measures between members of couples consisting of men with ED and sexually healthy women reporting infrequent satisfactory sexual intercourse underscores the importance of including partners in ED treatment discussions.

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Urology. 2007 Jan;69(1):163-5.
Immediate improvement in penile hemodynamics after cessation of smoking: previous results.
Sighinolfi MC, Mofferdin A, De Stefani S, Micali S, Cicero AF, Bianchi G.
Department of Urology, University of Modena, Modena, Italy. sighinolfic@yahoo.com

OBJECTIVES: To assess the chronologic relationship between the cessation of smoking and the restoration of erectile function. Smoking is associated with an increased risk of erectile dysfunction. METHODS: Twenty active smokers (20 to 40 cigarettes/day) affected by erectile dysfunction (International Index of Erectile Function 5-item score less than 21) were enrolled in the study. The mean age was 40 years. All the patients underwent penile color Doppler ultrasonography during the basic and dynamic phases (10 microg prostaglandin E1). A second Doppler evaluation was performed 24 to 36 hours after cessation of smoking. The peak systolic velocity (PSV) and end-diastolic velocity (EDV) were recorded. The PSV and EDV cutoff value was 30 cm/s and 5 cm/s, respectively. RESULTS: Of the 20 patients, 10 (50%) had normal PSV values but only 5 (25%) had normal EDV values at the baseline Doppler evaluation. All the patients (100%) had normal PSV values at the second penile Doppler evaluation after smoking withdrawal, and 17 (85%) also had normal EDV values. The average PSV was 40.1 and 50.3 cm/s (P = 0.09) and the mean EDV was 6.8 and 2.4 cm/s (P <0.01) at the baseline penile Doppler examination and after smoking withdrawal, respectively. CONCLUSIONS: Within 24 to 36 hours of the cessation of cigarette smoking, the color Doppler parameters demonstrated a significant improvement in EDV and a trend toward an increase in PSV. Additional clinical evaluation is required to further characterize the expeditious improvement in erectile function after the cessation of smoking.

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Curr Med Res Opin. 2006 Dec;22(12):2497-506.
Comorbid LUTS and erectile dysfunction: optimizing their management.
Kaminetsky J.
Department of Urology, New York University School of Medicine, New York, NY 10016, USA. jckammd@att.net

BACKGROUND AND SCOPE: Lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH), and sexual dysfunction such as erectile dysfunction (ED), are highly prevalent in men over the age of 50. LUTS and ED have a negative impact on sexual function and when comorbid, result in reduced quality of life. The goal of this article is to discuss the relationship between ED and LUTS, describe the diagnostic workup of these disorders, explore the current treatment options, and examine how treatments may affect this population. Medline (1980-2006), Cochrane reviews, and the American Urological Association 2006 General Meeting abstracts were searched for relevant clinical trials and reviews with the terms: benign prostatic hyperplasia, lower urinary tract symptoms, erectile dysfunction, sexual dysfunction, alpha-adrenergic receptor antagonists, alpha-blockers, 5alpha-reductase inhibitors, phosphodiesterase type-5 inhibitors, transurethral resection of the prostate, transurethral microwave thermotherapy, transurethral needle ablation, adverse events, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, finasteride, sildenafil, tadalafil, vardenafil. However, because of the volume of literature, this article is not a systematic review. FINDINGS: Although age is an independent risk factor for both LUTS and ED, studies report that LUTS is also an independent risk factor for ED. Treatments for LUTS include pharmacologic, minimally invasive, and surgical therapies. Among pharmacologic options, alpha1-adrenergic receptor (alpha1-AR) antagonists provide effective treatment with a low risk of sexual side-effects; some of these drugs have been reported to improve sexual function. The treatment of LUTS may improve ED. Phosphodiesterase type 5 inhibitors (PDE-5s) are considered first-line therapy for ED. Comorbid LUTS and ED are treated with an alpha1-AR antagonist and a PDE-5; however, this combination must be used with caution because of vasodilatory adverse events associated with both classes of drugs. CONCLUSIONS: Optimal management includes screening to identify patients with comorbid LUTS and ED, and the use of treatments that minimize both vasodilatory and sexual side-effects.
  
Previous ED Research: 2002-2006   
The Erectile Dysfunction File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Erectile Dysfunction, click HERE.
 

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