Ronald W. Lewis

Summary of the recommendations on sexual dysfunctions in men

INTRODUCTION Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. AIM To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. METHODS An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures.  New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. RESULTS Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to mens and womens individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronies disease; and priapism. CONCLUSIONS Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

Definitions/epidemiology/risk factors for sexual dysfunction.

INTRODUCTION Accurate estimates of prevalence/incidence are important in understanding the true burden of male and female sexual dysfunction and in identifying risk factors for prevention efforts. This is the summary of the report by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction. AIM The main aim of this article is to provide a general overview of the definitions of sexual dysfunction for men and women, the incidence and prevalence rates, and a description of the risk factors identified in large population-based studies. METHODS Literature regarding definitions, descriptive and analytical epidemiology of sexual dysfunction in men and women were selected using evidence-based criteria. For descriptive epidemiological studies, a Prins score of 10 or higher was utilized to identify population-based studies with adequately stringent criteria. This report represents the opinions of eight experts from five countries developed in a consensus process and encompassing a detailed literature review over a 2-year period. MAIN OUTCOME MEASURES The study aims to provide state-of-the-art prevalence and incidence rates reported for each dysfunction and stratified by age and gender. Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. RESULTS A wealth of information is presented on erectile dysfunction, its development through time, and its correlates. The field is still in need of more epidemiological studies on the other mens sexual dysfunction and on all womens sexual dysfunctions. CONCLUSIONS A review of the currently available evidence from epidemiological studies is provided.

ORIGINAL ARTICLESORIGINAL ARTICLES: Definitions/Epidemiology/Risk Factors for Sexual Dysfunction

INTRODUCTION Accurate estimates of prevalence/incidence are important in understanding the true burden of male and female sexual dysfunction and in identifying risk factors for prevention efforts. This is the summary of the report by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction. AIM The main aim of this article is to provide a general overview of the definitions of sexual dysfunction for men and women, the incidence and prevalence rates, and a description of the risk factors identified in large population-based studies. METHODS Literature regarding definitions, descriptive and analytical epidemiology of sexual dysfunction in men and women were selected using evidence-based criteria. For descriptive epidemiological studies, a Prins score of 10 or higher was utilized to identify population-based studies with adequately stringent criteria. This report represents the opinions of eight experts from five countries developed in a consensus process and encompassing a detailed literature review over a 2-year period. MAIN OUTCOME MEASURES The study aims to provide state-of-the-art prevalence and incidence rates reported for each dysfunction and stratified by age and gender. Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. RESULTS A wealth of information is presented on erectile dysfunction, its development through time, and its correlates. The field is still in need of more epidemiological studies on the other mens sexual dysfunction and on all womens sexual dysfunctions. CONCLUSIONS A review of the currently available evidence from epidemiological studies is provided.

Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway.

Relaxation of the smooth muscle cells in the cavernosal arterioles and sinuses results in increased blood flow into the penis, raising corpus cavernosum pressure to culminate in penile erection. Nitric oxide, released from non-adrenergic/non-cholinergic nerves, is considered the principle stimulator of cavernosal smooth muscle relaxation, however, the inhibition of vasoconstrictors (that is, norepinephrine and endothelin-1, refs. 5–9) cannot be ignored as a potential regulator of penile erection. The calcium-sensitizing ρ-A/Rho-kinase pathway may play a synergistic role in cavernosal vasoconstriction to maintain penile flaccidity. Rho-kinase is known to inhibit myosin light chain phosphatase, and to directly phosphorylate myosin light-chain (in solution), altogether resulting in a net increase in activated myosin and the promotion of cellular contraction. Although Rho-kinase protein and mRNA have been detected in cavernosal tissue, the role of Rho-kinase in the regulation of cavernosal tone is unknown. Using pharmacologic antagonism (Y-27632, ref. 13, 18), we examined the role of Rho-kinase in cavernosal tone, based on the hypothesis that antagonism of Rho-kinase results in increased corpus cavernosum pressure, initiating the erectile response independently of nitric oxide. Our finding, that Rho-kinase antagonism stimulates rat penile erection independently of nitric oxide, introduces a potential alternate avenue for the treatment of erectile dysfunction.

Patient and partner satisfaction with Viagra (sildenafil citrate) treatment as determined by the erectile dysfunction inventory of treatment satisfaction questionnaire

OBJECTIVES To assess the efficacy and safety of Viagra (sildenafil citrate) in male outpatients with erectile dysfunction and patient and partner satisfaction with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). METHODS A total of 247 patients with erectile dysfunction of broad-spectrum etiology were treated in a randomized, double-blind, parallel-group, multicenter study conducted at outpatient clinics. Patients receiving oral sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo during a 12-week period. The principal efficacy measures were responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) on the International Index of Erectile Function and three global efficacy questions. Patient and partner satisfaction with treatment were assessed, for the first time, using the EDITS questionnaire. RESULTS Efficacy scores for the International Index of Erectile Function questions and the global efficacy questions were significantly higher for patients receiving sildenafil than for those receiving placebo (P <0.001). Both patients and partners receiving sildenafil also had significantly higher EDITS scores than those receiving placebo (P <0.001). Adverse events were chiefly mild or moderate. Two patients receiving sildenafil and none receiving placebo discontinued treatment because of adverse events. CONCLUSIONS Sildenafil was an effective, well-tolerated treatment for erectile dysfunction in an outpatient setting. Partner evaluations corroborated patient assessments. The results from the EDITS questionnaire indicated that after 12 weeks of receiving sildenafil both patients and partners reported higher levels of treatment satisfaction relative to placebo.

Epidemiology of erectile dysfunction

Epidemiologic studies are descriptive and analytical. The prevalence of erectile dysfunction in various community studies has varied from as low of 7% to as high as 52%. The prevalence of erectile dysfunction increases with age. Incidence data are scarce but a recent study of white males in the United States described an incidence of 26 cases per 1000 man-years. Risk factors for erectile dysfunction include certain medications, such as cardiovascular medications and psychotropic drugs, and chronic diseases, particularly neurologic diseases and diabetes mellitus.

CHRONIC TREATMENT WITH FINASTERIDE DAILY DOES NOT AFFECT SPERMATOGENESIS OR SEMEN PRODUCTION IN YOUNG MEN

PURPOSE Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.

Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection

The RhoA/Rho-kinase pathway mediates vasoconstriction in the cavernosal circulation. Inhibition of this pathway leads to penile erection in the in vivo rat model. These studies examined the hypothesis that nitric oxide (NO) inhibits RhoA/Rho-kinase signaling as part of normal erection. The results show that NO causes increased intracavernosal pressure and that this response is potentiated by prior treatment with a threshold dose of the Rho-kinase inhibitor, (+)-(R)-trans-4-(1-Aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride, monohydrate (Y-27632). These results support the hypothesis that NO inhibits Rho-kinase-induced cavernosal vasoconstriction during erection.

Pathophysiology of varicocele in nonhuman primates: Long-term seminal and testicular changes

Varicocele was surgically induced in monkeys to study the long-term effects of the condition on seminal and testicular parameters. Sperm motility was depressed but improved after varicocelectomy. Sperm concentration was less affected, but sperm morphology showed long-term degenerative changes, i.e., for more than 2 years. Testicular blood flow was depressed acutely but returned to normal after 2 years. Electron microscopy showed changes in the basal lamina and spermatogonia that persisted throughout the study. Left adrenalectomy, at the time of varicocele induction, did not alter the development of varicocele-related changes. The sequence of changes suggests that the effects of this experimental varicocele may be reversed in the monkey model through changes in collateral and ancillary revascularization.

External vacuum therapy for erectile dysfunction: use and results

SummaryThis review assesses the continuing role of noninvasive vacuum therapy as treatment for erectile dysfunction and discusses the action of negative pressure in producing assisted erection. Though recent research in this area has centered on the development of pharmaceutical therapies, vacuum-therapy programs appear to be a consistent long-term option for patients experiencing either chronic or occasional impotence of any etiology. Very little testing is required before the initiation of vacuum treatment, and the overall clinical success rate is approximately 90%. Significant success has been reported in more difficult patient populations, including those with veno-occlusive disorders and explanted penile prostheses. Vacuum therapy may also be used in conjunction with other therapies to enhance results. Contraindications to the use of vacuum therapy are few and primarily include patients with unexplained intermittent priapism and bleeding disorders. Side effects such as occasional numbness, pain, penile bruising, or petechiae have a low incidence. A recently reported survey of 5, 847 vacuum users showed that 83.5% of patients continue to use the device for intercourse as desired. Patients should receive individual instruction in the use of these devices and should expect a learning or practice period to achieve optimal results. As newer treatments for erectile dysfunction gain increasing attention, it should be kept in mind that nearly every patient showing impotence of any degree or duration as well as patients who have failed other therapeutic choices are candidates for vacuum therapy.