Dimitris Hatzichristou

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.

Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia

CONTEXT This review focuses on the relationship among sexual dysfunction (SD), lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and related therapies. OBJECTIVE We reviewed the current literature to provide an overview of current data regarding epidemiology and pathophysiology of SD and LUTS. Moreover, we analysed the impact of currently available therapies of LUTS/BPH on both erectile dysfunction (ED) and ejaculatory dysfunction and the effect of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with ED and LUTS. EVIDENCE ACQUISITION We conducted a Medline search to identify original articles, reviews, editorials, and international scientific congress abstracts by combining the following terms: benign prostatic hyperplasia, lower urinary tract symptoms, sexual dysfunction, erectile dysfunction, and ejaculatory dysfunction. EVIDENCE SYNTHESIS We conducted a comprehensive analysis of more relevant general population-based and BPH/LUTS or SD clinic-based trials and evaluated the common pathophysiologic mechanisms related to both conditions. In a further step, the overall impact of current BPH/LUTS therapies on sexual life, including phytotherapies, novel drugs, and surgical procedures, was scrutinized. Finally, the usefulness of PDE5-Is in LUTS/BPH was critically analysed, including preclinical and clinical research data as well as possible mechanisms of action that may contribute to the efficacy of PDE5-Is with LUTS/BPH. CONCLUSIONS Community-based and clinical data demonstrate a strong and consistent association between LUTS and ED, suggesting that elderly men with LUTS should be evaluated for SD and vice versa. Pathophysiologic hypotheses regarding common basics of LUTS and SD as discussed in the literature are (1) alteration of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, (2) enhancement of RhoA-Rho-kinase (ROCK) contractile signalling, (3) autonomic adrenergic hyperactivity, and (4) pelvic atherosclerosis. The most important sexual adverse effects of medical therapies are ejaculation disorders after the use of some α-blockers and sexual desire impairment, ED, and ejaculatory disorders after the use of α-reductase inhibitors. Minimally invasive, conventional, and innovative surgical treatments for BPH may induce both retrograde ejaculation and ED. PDE5-Is have demonstrated significant improvements in both LUTS and ED in men with BPH; combination therapy with PDE5-Is and α1-adrenergic blockers seems superior to PDE5-I monotherapy.

The 'effectiveness' scale--therapeutic outcome of pharmacologic therapies for ED: an international consensus panel report.

Despite availability of outcome measures and scales for assessing erectile dysfunction (ED) treatment efficacy, guidelines are not available for assessing broader therapeutic outcomes or defining treatment failure in ED. An International Consensus Advisory Panel was convened to develop guidelines, definitions and a new algorithm for evaluating treatment effectiveness in ED. These new guidelines are recommended for use in both research and clinical practice. A multidisciplinary, international panel, consisting of 11 senior researchers and clinicians, was convened to address pertinent issues concerning therapeutic outcome assessment for ED. The panel utilized a modified Delphi method of consensus development and proposed a new model for outcomes assessment. This model is inherently testable, using existing instruments and current methods of assessment. Following a comprehensive literature review and discussion, the Panel recommended adoption of a new treatment effectiveness conceptual framework or theoretical model for assessing therapeutic outcomes in ED. Treatment effectiveness is presumed to be a combined function of two other factors, treatment response and treatment satisfaction. Treatment response is based on the combined assessment of efficacy and tolerability, and treatment satisfaction on the combined assessment of patient and partner satisfaction. Taken together, these two domains define an overall domain of treatment effectiveness. This therapeutic index would be derived by independently assessing treatment efficacy and satisfaction by means of event logs, questionnaires or the more typical patient interview methods. In conclusion, the Ad Hoc Advisory Consensus Panel recommends adoption of a new framework or conceptual model for conducting ED outcome trials or clinical research. The concept of ‘treatment effectiveness’ is proposed as a new ‘umbrella concept’ or distal outcome to be evaluated.

Effects of oral phentolamine, taken before sleep, on nocturnal erectile activity: a double-blind, placebo-controlled, crossover study.

The objective of this study was to determine the effects of oral phentolamine, administered before sleep, on nocturnal penile erectile activity of men with mild to moderate erectile dysfunction (ED). We studied five patients with mild to moderate ED (mean age 34.8±8.13 and mean duration of ED 31.8±23.5 months), in a double-blind, placebo-controlled, crossover study. All patients received oral phentolamine (VasomaxTM) at a dose of 40 mg and placebo for three consecutive nights respectively and were submitted to nocturnal penile tumescence and rigidity monitoring (NPTR) with the Rigiscan® device. NPTR parameters of the two 3-night recordings were evaluated and compared. Administration of oral phentolamine before sleep was associated with a statistically significant increase in the number of erectile events with rigidity ≥60% lasting ≥10 min (P=0.02), as well as the rigidity activity units (RAU) value per hour sleep, both at the base (P=0.023) and the tip of the penis (P=0.019). The number of events as measured by Rigiscan software (20% change in circumference), as well as tumescence activity units (TAU)/h values did not show any statistical difference. No adverse effects were recorded. It is concluded that oral phentolamine administered before sleep enhanced NPTR parameters associated with the quality of the erectile events. Such results provide a pathway for the development of a prevention strategy for ED. Future studies will elucidate whether vasoactive agents taken on a regular basis before sleep, can prevent ED in men at risk, protecting also minimally and moderately impotent patients to become moderately and severely impotent respectively.

Diagnosing Sexual Dysfunction in Men and Women: Sexual History Taking and the Role of Symptom Scales and Questionnaires

INTRODUCTION A detailed sexual history is the cornerstone for all sexual problem assessments and sexual dysfunction diagnoses. Diagnostic evaluation is based on an in-depth sexual history, including sexual and gender identity and orientation, sexual activity and function, current level of sexual function, overall health and comorbidities, partner relationship and interpersonal factors, and the role of cultural and personal expectations and attitudes. AIM To propose key steps in the diagnostic evaluation of sexual dysfunctions, with special focus on the use of symptom scales and questionnaires. METHODS Critical assessment of the current literature by the International Consultation on Sexual Medicine committee. MAIN OUTCOME MEASURES A revised algorithm for the management of sexual dysfunctions, level of evidence, and recommendation for scales and questionnaires. RESULTS The International Consultation on Sexual Medicine proposes an updated algorithm for diagnostic evaluation of sexual dysfunction in men and women, with specific recommendations for sexual history taking and diagnostic evaluation. Standardized scales, checklists, and validated questionnaires are additional adjuncts that should be used routinely in sexual problem evaluation. Scales developed for specific patient groups are included. Results of this evaluation are presented with recommendations for clinical and research uses. CONCLUSION Defined principles, an algorithm and a range of scales may provide coherent and evidence based management for sexual dysfunctions.

Low-Intensity Extracorporeal Shock Waves Therapy (LI-ESWT) for the treatment of erectile dysfunction: Where do we stand?

Almost two decades after the phosphodiesterase type 5 inhibitor (PDE5-I) revolution in the management of erectile dysfunction (ED), the restoration of natural erections remains the ultimate goal of any treatment. The achievement of this goal, however, remains an unmet need [1]. Extracorporeal shock waves have been used in urology not only for stones but also for the treatment of Peyronie’s disease and chronic pelvic pain [2]. In 2010, Vardi et al published their first paper, which introduced the use of lowintensity extracorporeal shock wave therapy (LI-ESWT) for ED [3]. In recent years, that group published results from a series of randomized sham-controlled trials clearly demonstrating that the method is tolerable and effective, even in patients who are nonresponders to PDE5-Is [4,5]. Several other research groups followed and produced promising results, with a range of improvement in International Index of Erectile Function (IIEF) scores between 5.3 and 7.6 points [6], similar to the published data on PDE5-I clinical trials [1]. Such data were enthusiastically accepted by the scientific community, as ideally, ED therapy should be ‘‘simple, non-invasive and non-painful with a high success rate and few minor side effects’’ [7]. A recent systemic review and meta-analysis shed light on various critical aspects of this novel treatment modality, suggesting that, with more robust data from randomized controlled trials (RCTs), LI-ESWT may have the potential to be the firstchoice noninvasive treatment for patients with ED [6]. Revolutionary medical discoveries, especially in the era of high Internet access, allows ambitious clinicians, eager

Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference)

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Development of a new optical device and its feasibility in prostate cancer detection.

Aim: To develop a new optical device (prostate optical device, POD) for assessment of prostate tissue stiffness and evaluate its sensitivity and specificity in prostate cancer detection. Patients and Methods: POD was tested in prostate phantoms and in patients with indications for prostate biopsy. Its sensitivity and specificity were compared to digital rectal examination (DRE) and transrectal ultrasonography (TRUS). Results: POD was able to identify stiffness differences on each prostate phantom. 45 patients were included in the study. Sensitivity of TRUS (40%) was significantly lower to POD (85.7%) and DRE (74.3%) (p = 0.000 and p = 0.003, respectively). There was no statistical difference between POD and DRE (p = 0.221). The combination of POD and DRE showed the highest sensitivity (88.6%), positive predictive value (81.6%), and negative predictive value (42.9%) among all diagnostic tests. Conclusions: POD identified prostatic stiffness differences with the same sensitivity of DRE performed by an experienced urologist providing an objective indication for prostate biopsy and early prostate cancer detection.

Effects of low-intensity shock wave therapy (LiST) on the erectile tissue of naturally aged rats

Low-intensity shock wave therapy (LiST) improves erectile function in patients with erectile dysfunction (ED), probably by promoting angiogenesis as suggested by studies on animals with comorbidities as disease associated ED models. We aim to investigate the effects of LiST on erectile tissue of healthy, naturally aged rats. Twelve naturally aged male rats were randomized into two groups: control group (n = 6) and LiST-treatment group (n = 6). Young rats (8 weeks) (n = 6) was also used as control. Each rat in treatment group received 300 shock waves with an energy flux density of 0.09 mJ/mm2 at 2 Hz. Sessions were repeated three times/week for 2 weeks, followed by a 2-week washout period. Real-time RT-PCR for the expressions of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), nerve growth factor (NGF), neuronal NOS (nNOS), as well as α1 and α2-adrenergic receptors (α1AR, α2AR) was performed, followed by immunohistochemical analysis (IHC) to evaluate protein expression. The expressions of VEGF, eNOS, and α2AR/α1AR ratio were increased after LiST (p = 0.039, p = 0.008, and p = 0.006 respectively). The increase of VEGF, eNOS, and α2AR was confirmed in IHC (p = 0.013, p = 0.092, and p = 0.096, respectively). The increase of VEGF and eNOS seem to play key role in the mechanism of action of LiST, apparently by inducing angiogenesis. The altered expression of α1/α2-adrenergic receptors could indicate a decrease in sympathetic activity. LiST showed to partially reverse changes associated with aging in erectile tissue of rats, which supports future research for ED prevention.

Penile Cancer and Sexuality

Penile cancer is a rare disease. The most common type is squamous cell carcinoma responsible for about 95 % of cases reported. The remaining 5 % have other morphology such as melanoma, basal cell carcinoma, and adenocarcinoma of the penis [1]. There is a wide geographical diversity of the disease. In Western countries, it is quite rare with an annual incidence of less than 1 per 100,000 males. In populations of other countries such as Africa, Asia, and South America, the incidence is higher.