Federico Dehò

Pharmacological management of erectile dysfunction

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first‐line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy‐safety profile in all patient categories. Apomorphine SL is a dopamine D1‐ and D2‐receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy‐safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second‐line treatment is high but the attrition rate remains significant.

Common grounds for erectile dysfunction and coronary artery disease.

Purpose of review Evidence is accumulating to consider erectile dysfunction as a vascular problem. This review focuses on background, pathophysiological mechanisms and clinical evidence of the link between erectile dysfunction and coronary artery disease. Recent findings The link between erectile dysfunction and coronary artery disease is suggested by the following. (1) Common risk factors for atherosclerosis are frequently found in erectile dysfunction. (2) Erectile dysfunction is frequently found in vascular syndromes such as coronary artery disease, hypertension, cerebrovascular disease, peripheral arterial disease and diabetes. (3) A similar pathogenic involvement of the NO pathway leading to impairment of endothelium-dependent vasodilatation and late structural vascular abnormalities is shared by erectile dysfunction and vascular disorders. Given this background, the ‘artery-size hypothesis’ is a recently proposed pathophysiological mechanism to explain the link between sexual dysfunction and myocardial ischemia. Summary Erectile dysfunction and coronary artery disease appear to be linked tightly each other.

Brain activation patterns during video sexual stimulation following the administration of apomorphine: Results of a placebo-controlled study

OBJECTIVES To evaluate the in vivo effect of apomorphine sublingual versus placebo on cortical and subcortical brain activation during video sexual stimulation. METHODS Ten patients with psychogenic erectile dysfunction and six potent controls underwent functional magnetic resonance of the brain during video sexual stimulation after the administration of either apomorphine sublingual 4mg or placebo following a randomized, double blind design. Functional magnetic resonance sessions were performed with a 7-day interval. RESULTS In potent controls, viewing erotic versus neutral films induced bilateral activations in a network of occipito-parietal and temporal inferior regions, in dorsolateral and premotor frontal cortex, in anterior temporal limbic areas and the thalamus, which were comparable to the patient activations during erotic stimulation in the placebo condition. However, a striking difference was found in patients, who demonstrated a significant and extended activation in the cingulate gyrus, frontal mesial and frontal basal cortex, bilaterally, in comparison with potent controls. These activated neural systems were modulated by apomorphine administration which produced a picture that was similar to the one seen in potent controls. In patients with spychogenic erectile dysfunction apomorphine sublingual caused an increase in the extension of the activated networks, plus additional activation foci in subcortical and deep structures, namely in the nucleus accumbens, hypothalamus and mesencephalon: this activation was greater than that seen with placebo. Interestingly, a down-regulation in the frontal basal and temporal limbic cortex was present as shown by a decrease of functional magnetic resonance imaging signal reflecting a deactivation of these regions. CONCLUSIONS Apomorphine significantly enhances the activation of cortical and subcortical brain function during video sexual stimulation. Patients with psychogenic erectile dysfunction may have an underlying functional abnormality of the brain acting as a previously unrecognised aetiological factor.

Initial Extended Transrectal Prostate Biopsy—Are More Prostate Cancers Detected With 18 Cores Than With 12 Cores?

PURPOSE We retrospectively investigated the detection rates of prostate cancer, high grade prostatic intraepithelial neoplasia and atypical glands suggestive of carcinoma by initial 18 and 12-core prostate biopsy. MATERIALS AND METHODS A total of 3,460 consecutive patients with prostate specific antigen between 2.5 and 15 ng/ml underwent 12 (1,684) or 18 (1,776) core prostate biopsy under local anesthesia at 2 departments that adopted the same indications for performing biopsy. Biopsies were evenly distributed throughout the prostate in 6 sectors. In the 12-core prostate biopsy group 2 samples were obtained from each sector and in the 18-core prostate biopsy group 1 additional core was taken from each sector. RESULTS The cancer detection rate in patients who underwent 18-core prostate biopsy was not different from the rate in those who underwent 12-core prostate biopsy (39.9% and 38.4%, p = 0.37), nor did the detection of atypical glands suggestive of carcinoma differ significantly between the 2 groups (2.9% and 3.3%, respectively, p = 0.33). However, 18-core prostate biopsy detected a significantly higher percent of cases of high grade prostatic intraepithelial neoplasia (20.0% vs 12.9%, p = 0.001). The cancer detection rate was higher with 18 than with 12-core prostate biopsy in patients with a prostate volume of 55 cc or greater (31.5% vs 24.8%, p = 0.01) but not in those with a prostate volume of less than 55 cc (54.3% and 53.0%, respectively, p = 0.7). Moreover, we determined that patients with positive digital rectal examination findings do not need 18-core prostate biopsy as opposed to 12-core prostate biopsy. CONCLUSIONS Compared with 12-core prostate biopsy, 18-core prostate biopsy detects significantly more cases of high grade prostatic intraepithelial neoplasia. However, 18-core prostate biopsy detects a significantly higher number of cancer only in patients with a prostate volume of 55 cc or greater.

Remembered International Index of Erectile Function domain scores are not accurate in assessing preoperative potency in candidates for bilateral nerve-sparing radical retropubic prostatectomy

INTRODUCTION The reliability of reported postoperative data in patients undergoing nerve-sparing radical retropubic prostatectomy is often limited because the degree of sexual function (SF) has not been assessed objectively both before and after treatment. Most reports include only a retrospective chart review, and there is a question of whether such data are accurate. AIM To test the agreement between a remembered International Index of Erectile Function (IIEF) score, which targeted SF regarding a period preceding the surgery by 6 months and a real-time IIEF, 4 weeks prior to surgery, in candidates for bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP). METHODS From May 2005 to May 2006, 333 consecutive patients were candidates for BNSRRP at our institution. Upon admission on the day prior to surgery, each patient was asked to complete a set of validated questionnaires including both a remembered and a real-time IIEF. Two-tailed Students t-test, chi2 test, Pearson correlation coefficient, multivariate regression analyses, and interrater agreement (kappa) were used to test the agreement between the two assessments. MAIN OUTCOME MEASURES Assessing the preoperative SF characteristics of candidates for a BNSRRP, and testing the reliability of a remembered IIEF with the interrater agreement (kappa) test. RESULTS Mean scores for the remembered IIEF were overall better than the real-time IIEF scores, as supported by direct comparison of the mean IIEF domain scores. Univariate correlation analysis and multivariate regression analysis indicated a significant correlation in the quality of the SF during the two periods. However, the remembered IIEF scores did not show a good statistical agreement with those of the real-time assessment, as demonstrated by the interrater agreement analysis. CONCLUSIONS Because of the lack of significant agreement between remembered and real-time IIEF scores, the present findings indicate that remembered IIEF should not be used to assess SF in a real-life clinical setting in candidates for BNSRRP.

Clinical update on phosphodiesterase type-5 inhibitors for erectile dysfunction

Erectile dysfunction (ED) affects the sexual lives of millions of men. The first-line oral pharmacotherapy for most ED patients is phosphodiesterase type-5 (PDE-5) inhibitors, of which three are available. Sildenafil is the most widely prescribed oral agent for ED and has a very satisfactory efficacy–safety profile in all patient categories. Tadalafil and vardenafil were introduced in the European Union and in the United States in 2003 and 2004, respectively. The three PDE-5 inhibitors share many pharmacological and clinical characteristics, and each has unique features. This review, which is based on the contemporary literature on PDE-5 inhibitors, describes the chemical, pharmacological, and clinical features of sildenafil, vardenafil, and tadalafil. The first section reviews the pathophysiology of penile erection and PDE-5 inhibitor pharmacology. The second section summarizes data regarding efficacy and safety of the three drugs in treating ED in the general population as well as in selected patient categories.

Holmium laser enucleation of the prostate and holmium laser ablation of the prostate: indications and outcome.

Purpose of review Holmium laser enucleation of the prostate (HoLEP) has been proposed as an alternative to transurethral resection of the prostate and to open prostatectomy for patients with lower urinary tract symptoms because of large benign prostatic enlargement. The aim of this review is to critically analyze currently available evidence-based reports regarding HoLEP, with particular interest in long-term follow-up results. Recent findings The use of holmium laser for the treatment of benign prostatic hyperplasia was first reported in 1996. HoLEP seems to represent a valid alternative to both transurethral resection of the prostate and open prostatectomy, with valid long-term functional results, a low rate of short-term and long-term complications, and very low rates of reintervention. Summary HoLEP represents a valid alternative to both transurethral resection of the prostate and open prostatectomy for treatment of patients suffering from lower urinary tract symptoms due to benign prostatic enlargement. The recently published long-term follow-up data demonstrate the durability of functional results. HoLEP can be offered as the size-independent gold standard treatment of patients with lower urinary tract symptoms because of benign prostatic enlargement.

Penile implants in the era of oral drug treatment for erectile dysfunction

At present, patients with ED are most frequently treated with one of the available PDE5-I. There is unanimous agreement on the need for adequate counselling of patients before treatment, to reduce the rate of no response this therapy. Evidence supports the view that significantly many patients who initially do not respond to a PDE5-I could be salvaged by simply adding adequate counselling, in terms of dosing of the drug, necessity of adequate sexual stimulation, and pharmacokinetics of the drug [3]. Patients on oral drug therapy should also be counselled to use the pill for at least eight attempts before making a definitive evaluation of its effects. Patients who fail to respond to oral pharmacotherapy often have an organic cause for and a severe degree of ED. Among these, motivated patients usually come back to their physician’s office asking for alternative therapeutic solutions. We feel that secondand third-line therapies should all be thoroughly explained to the patients; in our practice we have found that using material such as videos and anatomical drawings very helpful for the patient to understand exactly how every therapy works.

ORIGINAL RESEARCH—EJACULATORY DISORDERS: Quantitative Sensory Testing of Peripheral Thresholds in Patients with Lifelong Premature Ejaculation: A Case-Controlled Study

INTRODUCTION The main functional factors related to lifelong premature ejaculation (PE) etiology have been suggested to be penile hypersensitivity, greater cortical penile representation, and disturbance of central serotoninergic neurotransmission. AIMS To quantitatively assess penile sensory thresholds in European Caucasian patients with lifelong PE using the Genito-Sensory Analyzer (GSA, Medoc, Ramat Yishai, Israel) as compared with those of an age-comparable sample of volunteers without any ejaculatory compliant. METHODS Forty-two consecutive right-handed, fully potent patients with lifelong PE and 41 right-handed, fully potent, age-comparable volunteers with normal ejaculatory function were enrolled. Each man was assessed via comprehensive medical and sexual history; detailed physical examination; subjective scoring of sexual symptoms with the International Index of Erectile Function; and four consecutive measurements of intravaginal ejaculatory latency time with the stopwatch method. All men completed a detailed genital sensory evaluation using the GSA; thermal and vibratory sensation thresholds were computed at the pulp of the right index finger, and lateral aspect of penile shaft and glans, bilaterally. MAIN OUTCOME MEASURES Comparing quantitatively assessed penile thermal and vibratory sensory thresholds between men with lifelong PE and controls without any ejaculatory compliant. RESULTS Patients showed significantly higher (P < 0.001) thresholds at the right index finger but similar penile and glans thresholds for warm sensation as compared with controls. Cold sensation thresholds were not significantly different between groups at the right index finger or penile shaft, but glans thresholds for cold sensation were bilaterally significantly lower (P = 0.01) in patients. Patients showed significantly higher (all P < or = 0.04) vibratory sensation thresholds for right index finger, penile shaft, and glans, bilaterally, as compared with controls. CONCLUSIONS Quantitative sensory testing analysis suggests that patients with lifelong PE might have a hypo- rather than hypersensitivity profile in terms of peripheral sensory thresholds. The peripheral neuropathophysiology of lifelong PE remains to be clarified.

The ageing male and erectile dysfunction.

Erectile dysfunction is common in the ageing man and reliable therapies are needed. The pathophysiology of erectile dysfunction in this group mainly includes chronic ischaemia, which triggers the deterioration of cavernosal smooth muscle and the development of corporeal fibrosis. Assessing the ageing man with erectile dysfunction who seeks medical treatment should comprise a thorough medical and sexual history, a systemic and focused physical examination and selected blood tests. Oral drug therapy represents a safe and effective option for most ageing men.