Antonino Saccà

Are Infertile Men Less Healthy than Fertile Men? Results of a Prospective Case-Control Survey

BACKGROUND An association between either subfertility or infertility and an elevated risk of certain male cancers has been previously reported. Nothing is known about abnormalities in infertility and general health conditions. OBJECTIVE To assess whether men with male factor infertility (MFI) are overall less healthy than fertile men, regardless of the reasons for infertility. DESIGN, SETTING, AND PARTICIPANTS From September 2006 to September 2007, 344 consecutive European Caucasian men with MFI were enrolled in this prospective case-controlled study. Patients were compared with a control group of 293 consecutive age-comparable fertile men. Infertile men were consecutively attending the outpatient male reproductive clinic at a tertiary academic center. Fertile controls were consecutively recruited by use of advertisements posted within our hospital. MEASUREMENTS Comorbidities of patients and fertile men were objectively scored with the Charlson Comorbidity Index (CCI) according to the International Classification of Diseases modified ninth version (ICD-9-CM) codes. Multivariate linear regression models tested the association between predictors and CCI score, as a proxy of general health status. RESULTS According to the CCI scores, infertile men had a significantly higher rate of comorbidities compared with the fertile controls (CCI: 0.33 [0.8] vs 0.14 [0.5]; p<0.001; 95% CI: 0.08-0.29). Linear regression analyses showed that although educational status did not have an impact on CCI (β: 0.035; p=0.365), while CCI linearly increased with age (β: 0.196; p<0.001) and body mass index (BMI; β: 0.161; p<0.001). After adjusting for age, BMI, and educational status, a significantly lower CCI was calculated for fertile men and compared with MFI patients (β: -0.199; p<0.001). CONCLUSIONS These results show that MFI accounts for a higher CCI, which may be considered a reliable proxy of a lower general health status.

Is erectile dysfunction a reliable proxy of general male health status? The case for the International Index of Erectile Function-Erectile Function domain.

INTRODUCTION Erectile dysfunction (ED) has emerged progressively as a sentinel marker of cardiovascular disease (CVD). The correlation between ED and the burden arising from multiple comorbid conditions has been incompletely analyzed. AIM Assess whether erectile function, defined with the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, is associated with health-significant comorbidities scored with the Charlson comorbidity index (CCI). METHODS Clinical and hemodynamic variables of the last 140 consecutive patients who underwent penile color Doppler ultrasonography for new-onset ED were considered. Patients were assessed with a thorough medical and sexual history. Health-significant comorbidities were scored with the CCI. MAIN OUTCOME MEASURE Descriptive statistics and either linear or logistic regression models tested the association among IIEF-EF, hemodynamic parameters, and CCI, which was included in the model both as continuous and categorized variable (0 vs. ≥1). RESULTS Complete data were available for 138 patients (98.6%) (mean age 46.6 years [standard deviation 13.0]; range 21-75 years). CCI was 0, 1, and ≥2 in 94 (68.1%), 23 (16.7%), and 21 (15.25%) patients, respectively. Of all, 35 patients (79.5%) did not have a CVD comorbidity. Mean IIEF-EF was 13.7 (9.3). ED severity was no ED, mild, mild to moderate, moderate, and severe in 12 (9.1%), 28 (20.2%), 12 (9.1%), 23 (16.2%), and 63 (45.5%) patients, respectively. At multivariable linear regression analysis, CCI significantly worsened with increased age (β=0.33; P=0.001) and decreased IIEF-EF values (β=-0.25; P=0.01). At logistic regression analysis, age (odds ratio [OR]: 1.05; P=0.004) and IIEF-EF (OR: 0.95; P=0.04) emerged as significant predictors of categorized CCI. CONCLUSIONS Severity of ED, as objectively interpreted with IIEF-EF, accounts for a higher CCI, which may be considered a reliable proxy of a lower general male health status regardless of the etiology of ED.

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.

Drug Insight: oral phosphodiesterase type 5 inhibitors for erectile dysfunction.

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men. At present, first-line oral pharmacotherapy for most patients with ED is a phosphodiesterase type 5 (PDE-5) inhibitor, of which three are currently available worldwide. Sildenafil (Viagra®, Pfizer) has a very satisfactory efficacy–safety profile in all patient categories. The first PDE-5 inhibitor to reach the market, it is now the most widely prescribed oral agent for ED. Tadalafil (Cialis®, Lilly ICOS) and vardenafil (Levitra®, Bayer/GlaxoSmithKline) were introduced to the European Union and the US in 2003 and 2004, respectively. These three PDE-5 inhibitors share many characteristics, but each has unique features. This review describes the chemical, pharmacologic and clinical features of sildenafil, vardenafil and tadalafil as oral first-line treatments for ED. First, we describe the physiology of penile erection and PDE-5 inhibitor pharmacology, including chemistry, PDE selectivity, pharmacokinetics, and possible drug interactions. We then summarize data on the efficacy and safety profiles of the three PDE-5 inhibitors for the treatment of ED in the general population, in patients with diabetes mellitus and in men that have undergone bilateral nerve-sparing retropubic radical prostatectomy.

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.

Erectile Function Outcome after Bilateral Nerve Sparing Radical Prostatectomy: Which Patients May Be Left Untreated?

INTRODUCTION Several studies have shown that erectile function (EF) recovery in patients undergoing bilateral nerve sparing radical prostatectomy (BNSRP) improves significantly when phosphodiesterase type 5 inhibitors (PDE5) are administered following surgery. AIM The aim of this article was to identify patients who may recover EF after retropubic BNSRP (BNSRRP) without PDE5. METHODS We included 293 patients treated with BNSRRP at a single center. Postoperative EF recovery was defined as an EF domain score of the International Index of Erectile Function (IIEF) ≥22. No patient received any treatment for postoperative erectile dysfunction (ED). Kaplan-Meier curves assessed time to EF recovery according to patient age, preoperative EF, and Charlson comorbidity index (CCI). Univariable and multivariable Cox regression models tested the association between predictors and EF recovery. Finally, the rate of EF recovery of untreated patients after BNSRP was compared with a subset of patients with similar preoperative characteristics but receiving PDE5. MAIN OUTCOME MEASURE The main outcome measure of this article was the IIEF-EF domain score. RESULTS Overall, 105/293 (35.8%) reached an IIEF-EF ≥22 after a mean follow-up of 26.8 months. At multivariable analyses, age, preoperative IIEF-EF, and CCI achieved independent predictor status (all P≤0.04). Patients <55 years had a 72.4% EF recovery rate compared with 30% of patients >70 years (P<0.001). Similarly, preoperatively fully potent patients (IIEF-EF ≥26) had a 56.6% chance of recovering EF after surgery compared with 18% of patients with severe ED before surgery (P<0.001). The rate of EF recovery in untreated patients <55 years and with a pre-op IIEF-EF ≥22 was higher but did not differ significantly from comparable patients receiving PDE5 (P=0.11). CONCLUSIONS Overall, the rate of EF postoperative recovery in patients left untreated after surgery is modest (35.8%). Although younger patients with a good preoperative EF may experience good EF recovery rates even without any treatment, use of PDE5 after surgery further improved their functional outcomes. Therefore, a therapy for ED should be offered to all patients treated with BNSRP.

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.

Severe Vascular Complication after Implantation of a Three-Piece Inflatable Penile Prosthesis

We report a case of acute arterial ischemia and deep venous thrombosis due to compression of the external iliac vein and artery by the reservoir of a three-piece inflatable penile prosthesis.

Prostate Saturation Biopsy following a First Negative Biopsy: State of the Art

Introduction: Saturation prostate biopsy (SPBx) has been initially introduced to improve prostate cancer (PCa) detection rate (DR) in the repeat setting. Nevertheless, the optimal number and the most appropriate location of the cores, together with the timing to perform a second PBx and the eventual modification of the PBx protocols according to the different clinical situations, are matters of debate. The aim of this review is to perform a critical analysis of the literature about the actual role of SPBx in the repeat setting. Materials and Methods: We performed a systematic review of the literature since 1995 up to 2011. Electronic searches were limited to the English language, using the MEDLINE database. The key words ‘saturation prostate biopsy’ and ‘repeated prostate biopsy’ were used. Results: SPBx improves PCa DR if clinical suspicion persists after previous biopsy with negative findings and provides an accurate prediction of prostate tumor volume and grade, even if the issue about the number and locations of the cores is still a matter of debate. Conclusions: At present, SPBx seems to be really necessary in men with persistent suspicion of PCa after negative initial biopsy and probably in patients with a multifocal high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. In the remaining situations, adopting an individualized scheme is preferable.

Delay in Seeking Medical Help in Patients with New‐Onset Erectile Dysfunction Remained High Over and Despite the PDE5 Era—An Ecological Study

INTRODUCTION It is common knowledge among researchers that erectile dysfunction (ED) is an important sentinel marker of cardiovascular and overall mens health. AIM Determine whether the delay of time between ED onset and seeking medical help (DSH), considered as a proxy of awareness of the importance of ED for overall mens health, has shortened during the phosphodiesterase type 5 inhibitors (PDE5) era. METHODS Complete data from 619 patients seeking first medical help for new-onset ED as their primary disorder between July 2000 and July 2010 were analyzed (i.e., DSH, ED severity as defined by the International Index of Erectile Function-erectile function [IIEF-EF] domain score, patients awareness of any PDE5, and Charlson Comorbidity Index [CCI]). Analysis of variance tested DSH throughout the 10-year time frame. Cox regression models tested the association between predictors and DSH. MAIN OUTCOME MEASURES Assess if DSH has shortened throughout PDE5 era. Evaluate potential predictors of DSH. RESULTS Overall, mean DSH was 30.2 months (median 12.0; range 5-300 months). DSH shortened throughout the analyzed 10-year period (F = 1.918; P = 0.047), with a significant drop only from year 2009 (DSH up to year 2008 vs. from year 2009: 31.0 months [12.0] vs. 7.5 months [6.0], respectively; P < 0.001). Age, CCI, educational status, and ED severity did not significantly change over time. As a whole, 560 patients (90.5%) were aware of PDE5 at the time of their first office visit. PDE5 awareness emerged as an univarible and multivariable predictor of a shortened DSH. Conversely, DSH was not clearly associated with age, CCI, educational status, or ED severity. CONCLUSIONS Delay in seeking medical help in new-onset ED patients remained high over the PDE5 era, with a significant drop only from the year 2009. PDE5 awareness emerged as an independent predictor of shortening of this delay.