Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review.

BACKGROUND: Sexual dysfunction may be a side effect of treatment with antipsychotics, antidepressants, and other psychotropic drugs. AIM: To review the evidence concerning male sexual dysfunctions in patients taking psychotropic drugs to provide specific information to nonpsychiatric physicians for the management of these dysfunctions. METHODS: A systematic search of Medline and Embase databases was performed up to October 15th, 2020. We included randomized controlled trials comparing the effects of psychotropic drugs versus placebo or versus another drug of the same class, for at least 5 weeks. OUTCOMES: We considered studies whose male population could be evaluated separately from the female population and with a separate analysis of the different phases of the male sex cycle. RESULTS: We included 41 studies in the final review. There was a significant association between sexual dysfunction and antidepressant drug therapy, compared to placebo (decreased libido OR 1.89, 95% CI:1.40 to 2.56, 22 series, 11 trials, 7706 participants; erectile dysfunction OR = 2.28, 95% CI: 1.31 to 3.97; 11 trials, 3008 participants; ejaculatory dysfunction OR = 7.31, 95% CI: 4.38 to 12.20,19 trials, 3973 participants). When the effects of selective serotonin reuptake inhibitors (SSRIs) were evaluated separately from those of serotonin/norepinephrine reuptake inhibitors (SNRIs), the use of SNRIs but not that of SSRIs was characterized by significantly higher odds of erectile dysfunction compared to placebo. Only limited data were found regarding the effects of antipsychotics on the phases of the male sexual cycle, as it was shown that aripiprazole and risperidone showed lower and higher odds for erectile or ejaculatory dysfunction, respectively, compared to other atypical antipsychotics. CLINICAL IMPLICATIONS: Treatment of male sexual dysfunction in patients taking psychotropics requires a basic knowledge of the different drugs that affect sexual function with different mechanisms. STRENGTHS & LIMITATIONS: The effects of psychotropic drugs on erectile function and ejaculation were evaluated separately. The great variability of the mechanisms of action makes it difficult to make comparisons between the effects of the different classes of psychotropic drugs. CONCLUSIONS: Administration of antipsychotics affects male sexual function with different mechanisms, although the increase in prolactin values associated with the administration of first-generation antipsychotics and some atypical, such as risperidone, seems to play a primary role in determining male sexual dysfunction. Most antidepressants cause decreased libido, ejaculatory and erectile dysfunction, however the administration of SNRIs appears to be possibly associated with a specific risk of erectile dysfunction. Trinchieri M, Trinchieri M, Perletti G, et al. Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review. J Sex Med 2021;18:1354-1363.

Urinary side effects of psychotropic drugs: A systematic review and metanalysis.

OBJECTIVE: To evaluate the effects of psychotropic drugs on bladder function. MATERIALS AND METHODS: A systematic review was carried out by searching PubMed and Embase databases for randomized controlled trials enrolling patients treated with psychotropic drugs with available information on treatment-related urinary disorders. RESULTS: A total of 52 studies was selected. In antidepressant therapy, bladder voiding symptoms, rather than storage symptoms, were more frequently observed. Pooled analysis demonstrated a higher odds ratio (OR) of voiding  disorders in comparison with placebo (OR: 3.30; confidence interval [CI]: 1.90-5.72; 7856 participants; p < 0.001). Odds for voiding dysfunction was higher for tricyclic antidepressants and for Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) when compared to Selective Serotonin Reuptake Inhibitors (SSRIs). Treatment with antipsychotics was associated with heterogeneous urinary disorders  including emptying and storage disorders. OR for incontinence in patients with dementia taking  antipsychotics was higher than placebo (OR: 4.09; CI: 1.71-9.79, p = 0.002) with no difference between different atypical antipsychotics. Rate of voiding disorders was not different between conventional and atypical antipsychotics (OR: 1.64; CI: 0.79-3.39, p = 0.19), although quetiapine showed higher odds to cause voiding dysfunction than other atypical antipsychotics (OR: 2.14; CI: 1.41-3.26; p > 0.001). CONCLUSIONS: In patients taking tricyclic antidepressants or SNRIs, bladder voiding disorders, could be the side effects of therapy rather than symptoms of a urological disease. Patients treated with these drugs should be actively monitored for the appearance of urinary symptoms. Antipsychotic treatment is associated with various urinary side effects requiring a tailored approach.

Lithogenic Potential of Ureaplasma in Chronic Prostatitis.

INTRODUCTION: The role of Ureaplasma spp. (UPs) in the pathogenesis of chronic prostatitis is debated. The lithogenic potential of UPs could be a risk factor for the development of chronic prostatitis. METHODS: A total of 143 patients with identification of UPs were retrospectively selected from a database including patients with prostatitis-like symptoms who were studied according to the same protocol including clinical, microbiological and microscopic evaluation, and transrectal prostate ultrasound. A control group of patients with negative UPs was considered including 393 with chronic bacterial prostatitis (CBP), 42 patients with Chlamydia trachomatis (CT), and 781 patients with chronic pelvic pain syndrome. UPs and Mycoplasma hominis (MH) were identified using a semiquantitative assay. RESULTS: Calcifications were observed more frequently in patients with UPs (64%) than in patients with CBP without UPs (39%), CT infection (37%), and chronic pelvic pain syndrome (29%) (p < 0.0001). UPs were isolated in VB1 alone in 35 patients (urethral UPs), in expressed prostatic secretion (EPS) or post-massage urine (VB3) or sperm in 77 patients (prostatic UPs) and associated with other pathogens in 31 patients (associated UPs). Calcifications were more frequent in prostatic UPs (71%) and associated UPs (73%) than in urethral UPs (34%). Mean NIH-CPSI scores were not significantly different between groups, although mean WBC counts of sperm of patients with urethral UPs were significantly lower than in patients with prostatic UPs (p = 0.000) and associated UPs (p = 0.002). CONCLUSIONS: UPs identification in the urogenital fluids is related to higher rates of prostate calcifications. The ability of UPs to promote the formation of calcifications could be related to the chronicization of prostate infection. In particular, the presence of UPs in VB3/EPS/sperm is associated with higher rates of calcifications and high WBC sperm counts, suggesting a partial or full causative role of UPs in the pathogenesis of this disease.

Levofloxacin for NIH Category II Chronic Bacterial Prostatitis: A Real-Life Study.

BACKGROUND: Mounting worldwide resistance trends make the use of fluoroquinolone (FQ) antibacterial agents increasingly difficult. This is felt more acutely in the case of urogenital infections, which are mainly caused by Gram-negative pathogens. For years, levofloxacin and other FQs have been the first-line drugs for treating National Institutes of Health (NIH) category II chronic bacteria prostatitis (CBP). Eradication rates achieved by levofloxacin in the frame of randomized trials vary greatly, ranging between 71 and 86%. OBJECTIVES: This was a retrospective observational study to investigate the efficacy of levofloxacin against CBP in a real-life setting (urological outpatient wards). METHODS: A database including the clinical records of >2,500 CBP patients was reviewed. Patients were selected based on strict inclusion criteria. They were treated for 4 weeks with 500 mg levofloxacin per day, alone or combined with other antibacterials. Besides standard urological procedures including the 4-glass test for pathogen isolation, international symptom questionnaires (the NIH Chronic Prostatitis Symptom Index [NIH-CPSI] and International Prostate Symptom Score [IPSS]) were administered. RESULTS: Pathogen eradication was achieved in 79% of the cases treated with levofloxacin as a single agent and 87.8% of patients who received a combination of levofloxacin and azithromycin. The 11% increase in the eradication rate in the latter group is statistically significant. In addition, the levofloxacin-azithromycin combination caused a significant decrease in prostate volume and significantly increased the bladder-voided volume. IPSS and NIH-CPSI values and the urinary peak flow rate decreased to a similar extent in both treatment groups. No adverse effects were reported by patients belonging to either treatment group. CONCLUSION: Levofloxacin retained its therapeutic efficacy in patients assessed in a real-life setting, and high eradication rates were attained when it was administered as a single agent. A combination of an FQ with azithromycin induced a significant improvement of eradication rates. This strategy may be an interesting option in both first-referral and relapsing cases, although caution should be exercised when patients are at risk of developing arrhythmias, tendinitis, or other adverse effects.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

Computer-Assisted Quantitative Assessment of Prostatic Calcifications in Patients with Chronic Prostatitis.

BACKGROUND: The aim of this study was the development of quantitative assessment of prostatic calcifications at prostatic ultrasound examination by the use of an image analyzer. MATERIALS AND METHODS: A group of 82 patients was evaluated by medical history, physical, and transrectal ultrasound examination. Patients had a urethral swab, a 4-specimen study and culture of the seminal fluid. Patients were classified according to National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health. Subjective symptoms were scored by Chronic Prostatitis Symptom Index (CPSI) questionnaire. Ultrasound images were analyzed by the digital processing software Image J to quantitatively assess the presence of calcifications. RESULTS: Computer-assessed calcified areas were significantly higher in chronic bacterial prostatitis (n = 18; group II; 6.76 ± 8.09%) than in the chronic pelvic pain syndrome group IIIa (n = 26; 2.07 ± 1.01%) and IIIb (n = 38; 2.31 ± 2.18%). The area of calcification of the prostate was significantly related to the CPSI score for domains of micturition (r = 0.278, p = 0.023), Prostatic Specific Antigen values (r = 0341, p = 0.005), postvoiding residual urine (r = 0.262, p = 0.032), total prostate volume (r = 0.592, p = 0.000), and adenoma volume (r = 0.593; p = 0.000). CONCLUSIONS: The presence of calcifications is more frequently observed in patients with chronic bacterial prostatitis and is related to urinary symptoms.

Resistance of uropathogens to antibacterial agents: Emerging threats, trends and treatments.

Urinary tract infections are among the most common infectious diseases in humans. Today, resistance to nearly all antimicrobial classes is dramatically growing, and extremely drug-resistant or even pan-drug resistant pathogens are increasingly isolated around the world. It is foreseen that in the next decades the world will be facing a major medical emergency generated by the rapid spread of pathogens carrying resistance determinants of unprecedented power. Carbapenemase-producing Enterobacteriaceae, multidrug- resistant Enterococci and fluoroquinolone resistance determinants in both Gram-negative and Gram-positive uropathogens are among the greatest emergencies. In this article, the major emerging threats of particular interest to urologists are reviewed, worldwide resistance trends are illustrated, and novel and older - but still active - recommended drugs are summarized.

Multiparametric magnetic resonance imaging characteristics of normal, benign and malignant conditions in the prostate.

OBJECTIVES: To identify the multiparametric magnetic resonance imaging (mpMRI) characteristics of normal, benign and malignant conditions in the prostate. METHODS: Fifty-six histopathological whole-mount radical prostatectomy specimens from ten randomly selected patients with prostate cancer (PC) were matched with corresponding transverse mpMRI slices. The mpMRI was performed prior to biopsy and consisted of T2-weighted imaging (T2-WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced imaging (DCE) and magnetic resonance spectroscopic imaging (MRSI). RESULTS: In each prostate specimen, a wide range of histopathological conditions were observed. They showed consistent but overlapping characteristics on mpMRI. Normal glands in the transition zone showed lower signal intensity (SI) on T2-WI, lower ADC values and lower citrate peaks on MRSI as compared to the peripheral zone (PZ) due to sparser glandular elements and more prominent collagenous fibres. In the PZ, normal glands were iso-intense on T2-WI, while high SI areas represented cystic atrophy. Mimickers of well-differentiated PC on mpMRI were inflammation, adenosis, HG-PIN and post-atrophic hyperplasia. CONCLUSION: Each prostate is a unique mix of normal, benign and/or malignant areas that vary in extent and distribution resulting in very heterogeneous characteristics on mpMRI. Understanding the main concepts of this mpMRI-histopathological correlation may increase the diagnostic confidence in reporting mpMRI. KEYPOINTS: • In each prostate specimen a wide range of histopathological conditions was observed. • Interpretation of mpMRI may be difficult because benign conditions may mimic PC. • High signal intensity areas in the PZ on T2-WI represented cystic atrophy. • The TZ showed sparser glands and more collagenous fibres than the PZ.

The association between prostatitis and prostate cancer. Systematic review and meta-analysis.

OBJECTIVE: The main outcome of this review was the association between a history of clinical chronic prostatitis (NIH category II or III) and a histologically confirmed diagnosis of prostate cancer. MATERIALS AND METHODS: Crude odds ratios and 95% confidence intervals (CI) were calculated to analyze dichotomous data. For analysis of pooled data we adopted a random-effects model and the inverse variance weighing method. Heterogeneity was assessed by calculating the I2 value. RESULTS: Out of 2794 screened records, we retrieved 16 full-text articles written in English, reporting the data of 15 case-control studies, involving 422.943 patients. Pooled analysis resulted in a significant crude odds ratio of 1.83 (95% CI: 1.43 to 2.35; P < 0.00001). The total set of data showed considerable heterogeneity (I2 = 91%). Both the Egger's test and the Begg's test for funnel plot asymmetry did not reach statistical significance. The 'trim and fill' method applied to the funnel plot imputed 3 missing studies and the resulting adjusted estimate of the odds ratio was 2.12 (95% CI: 1.38 to 3.22). According to GRADE criteria, the overall quality of the meta-analysis data is low, mainly due to the presence of bias, confounders and extreme effect size outliers. Five among the included studies reported data assessed in 8015 African-American subjects. Pooled analysis resulted in a non-significant crude odds ratio of 1.59 (95% CI: 0.71 to 3.57; P = 0.26), and considerable heterogeneity (I2 = 90%). CONCLUSIONS: Meta-analysis of 15 case-control studies shows that a history of clinical chronic prostatitis can significantly increase the odds for prostate cancer in the general population, whereas such association in African-American individuals remains uncertain.

Herbal medicines for urinary stone treatment. A systematic review.

OBJECTIVE: To analyze the clinical evidence on the efficacy of phytotherapy in the treatment of calculi in the urinary tract. METHODS: To be eligible, full-length articles should include the results of randomized controlled trials enrolling patients affected by urolithiasis, reporting any comparison between an experimental herbal agent versus placebo or any active comparator, aimed at preventing the formation or facilitating the dissolution of calculi in any portion of the urinary tract. Fifteen databases were searched for relevant references. The primary outcomes investigated were (i) the reduction of stone size and/or number and (ii) the urinary excretion rates of calcium, urate, or oxalate. The secondary outcome of the review was the adverse effects (AE) of treatment. Risk of bias (ROB) and quality of the evidence were assessed according to Cochrane and GRADE guidelines. We performed a random-effect meta-analysis. RESULTS: 541 articles were retrieved and 16 studies were finally confirmed as eligible. Multiple Cochrane ROB tool items were rated as having high risk of bias in each analyzed trial report. Pooled analysis of continuous data could be performed for three different comparisons: (i) phytotherapy versus citrate as single agent (ii) phytotherapy versus placebo, (iii) preparation of Didymocarpus pedicellata (DP)--combined with other herbal agents--versus placebo. Results showed that citrate is superior to phytotherapy in significantly decreasing both the size of urinary stones (mean difference: phytotherapy, 0.42 mm higher; 95% CI: 0.23 to 0.6; Z = 4.42, P < 0.0001; I2 = 30%) and the urinary excretion rate of urate (mean difference: 42.32 mg/24h higher, 95% CI: 19.44 to 65.19; Z = 3.63, P = 0.0003; I2 = 96%), assessed after 3 months on-therapy. No significant differences in the excretion rates of urinary calcium or oxalate were found. The DP preparation was superior to placebo in inducing total clearance (risk ratio: 6.19, 95% CI: 2.60 to 14.74; Z = 4.12, P < 0.0001; I2 = 0%) and size reduction (mean difference: DP preparation, 4.93 mm lower; 95% CI: -9.18 to -0.67; Z = 2.27, P = 0.02; I2 = 99%) of renal and ureteral stones after 3 months of therapy. No significant differences in the inter-arm variation of excretion rates of urinary calcium or urate were found as result of the pooled phytotherapy-placebo comparison. Herbal remedies were in general devoid of side effects and in few cases citrate appeared to induce GI disturbances in a higher fraction of patients. Most reports did not provide inferential data concerning AE, and meta-analysis was not feasible. CONCLUSIONS: Citrate is more effective than phytotherapy in decreasing the size of existing calculi in the urinary tract and in decreasing the urinary excretion rate of uric acid. A preparation containing Didymocarpus pedicellata combined with other herbal agents induces stone size reduction and clearance significantly better than placebo. Mayor limitations in the applicability of these results are the low quality of the evidence and the multiple sources of bias assessed in the studies included in the present review.

Efficacy and safety of second-line agents for treatment of metastatic castration-resistant prostate cancer progressing after docetaxel. A systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review of the literature to assess the efficacy and the safety of second-line agents targeting metastatic castration-resistant prostate cancer (mCRPC) that has progressed after docetaxel. Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel). MATERIALS AND METHODS: We included phase III randomized controlled trials that enrolled patients with mCRPC progressing during or after first-line docetaxel treatment. Trials were identified by electronic database searching. The primary outcome of the review was overall survival. Secondary outcomes were radiographic progression-free survival (rPFS) and severe adverse effects (grade 3 or higher). RESULTS: Ten articles met the inclusion criteria for the review. These articles reported the results of five clinical trials, enrolling in total 5047 patients. The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. Compared to control cohorts (active drug-treated or placebo-treated), the significant overall survival advantages achieved were 4.8 months for enzalutamide (hazard ratio for death vs. placebo: 0.63; 95% CI 0.53 to 0.75, P < 0.0001), 4.6 months for abiraterone (hazard ratio for death vs. placebo: 0.66, 95% CI 0.58 to 0.75, P < 0.0001) and 2.4 months for cabazitaxel (hazard ratio for death vs. mitoxantrone-prednisone: 0.70, 95% CI 0.59 to 0.83, p < 0.0001). Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P < 0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P < 0.00001). Androgen synthesis inhibitors induced significant increases in risk ratios for adverse effects linked to elevated mineralocorticoid secretion, compared to placebo (risk ratio for hypokalemia: 5.75, 95% CI 2.08 to 15.90; P = 0.0008; risk-ratio for hypertension: 2.29, 95% CI 1.02 to 5.17; P = 0.05). CONCLUSIONS: In docetaxel-pretreated patients enzalutamide, abiraterone-prednisone and cabazitaxel-prednisone can improve overall survival of patients, compared to placebo or to best of care at the time of study (mitoxantrone-prednisone). Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. Further investigation is warranted to evaluate the benefit of combination or sequential administration of these agents. Large-scale studies are also necessary to evaluate the impact of relevant toxic effects observed in a limited number of patients (e.g., enzalutamide-induced seizures, orteronel-induced pancreatitis, and others).

Chlamydia†trachomatis infection is related to premature ejaculation in chronic prostatitis patients: results from a cross-sectional study.

INTRODUCTION: Chronic bacterial prostatitis (CBP) is reported to be a common finding in men with acquired premature ejaculation (PE). The impact of different pathogens on PE development in chronic prostatitis patients is, however, unknown. AIM: To assess a possible link between CBP caused by Chlamydia trachomatis (Ct) and PE. METHODS: A consecutive series of 317 patients with clinical and instrumental diagnosis of CBP due to Ct was enrolled (group A) and compared with data obtained from a control group of 639 patients with CBP caused by common uropathogen bacteria (group B). Prostatitis symptoms were investigated with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), while the ejaculatory status of patients was assessed using the PE Diagnostic Tool (PEDT). MAIN OUTCOME MEASURES: All participants were asked to complete the NIH-CPSI, the International Index of Erectile Function-15 erectile function domain (IIEF-15-EFD), the PEDT, and the Short Form (SF)-36 questionnaires. RESULTS: Patient groups A and B had comparable scores of NIH-CPSI (P = 0.07), IPSS (P = 0.32), and IIEF-15-EFD (P = 0.33) tests. PE was assessed in 118 patients in group A (37.2%) and in 73 subjects in group B (11.5%). The two groups are different in terms of PE prevalence (P < 0.0002). Compared with group B, group A showed significantly higher scores of the PEDT test (11.3 [±2.6] vs. 4.5 [±2.9], P < 0.0001) and lower scores of the SF-36 tool (96.5 [±1.1] vs. 99.7 [±1.3], P < 0.0001). In our multivariate model assessment, being positive for a Ct infection marker was independently associated with the PEDT score even after adjusting for age, smoking habit, body mass index, and education level (adjusted odds ratio = 3.21; 95% confidence interval: 2.02-4.27; P < 0.003). CONCLUSIONS: Patients affected by CBP due to Ct infection reported higher prevalence of PE and lower quality of life when compared with patients affected by CBP caused by traditional uropathogenic bacteria.

Psychological and sexological assessment of patients with chronic prostatitis.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by a multiform clinical presentation requiring a differentiated treatment based on different phenotypes including the psychosocial and sexual domains. The aim of this study was assessing the complex correlations between somatic, psychological, and sexual symptoms of CP/CPPS patients. MATERIALS AND METHODS: We performed a cross-sectional study on patients attending a Prostatitis Clinic. Patients were administered the following questionnaires: National Institutes of Health- Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Oxford Happiness Questionnaire (OHQ), and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). RESULTS: Linear regression analyses show highly significant correlations between scores of the NIH-CPSI and the scores of the GAD-7, PHQ-9 and OHQ psychometric questionnaires. IPSS scores correlate significantly with the psychometric scores only when a non-parametric analysis is performed. IIEF and PEDT sexual function scores did not correlate with any of the psychometric tests. NIH-CPSI scores correlate positively with most of the TEMPS-A profiles but the hyperthymic profile correlated negatively with the total and QoL NIH-CPSI and with PEDT scores. CONCLUSIONS: Scores measuring anxiety, depression, and psychological well-being in patients with CP/CPPS are strictly correlated with prostatitis-like symptoms although they are poorly correlated with symptoms of prostatism, as measured by IPSS, and not correlated with scores of sexual dysfunctions, as measured by IIEF and PEDT. A hyperthymic temperament may increase resilience against the disease.

Antimicrobial therapy for chronic bacterial prostatitis.

BACKGROUND: Chronic bacterial prostatitis (CBP) is frequently diagnosed in men of fertile age, and is characterized by a disabling array of symptoms, including pain in the pelvic area (for example, perineum, testicles), voiding symptoms (increased frequency and urgency, also at night; pain or discomfort at micturition), and sexual dysfunction. Cure of CBP can be attempted by long-term therapy with antibacterial agents, but relapses are frequent. Few antibacterial agents are able to distribute to the prostatic tissue and achieve sufficient concentrations at the site of infection. These agents include fluoroquinolones, macrolides, tetracyclines and trimethoprim. After the introduction of fluoroquinolones into clinical practice, a number of studies have been performed to optimize the antimicrobial treatment of CBP, and to improve eradication rates and symptom relief. OBJECTIVES: To assess and compare the efficacy and harm of antimicrobial treatments for chronic bacterial prostatitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, other national or international databases and abstracts from conference proceedings on 8 August 2012. SELECTION CRITERIA: We included all randomized controlled comparisons of one antimicrobial agent versus placebo or one or more comparator antimicrobial agents, combined or not with non-antimicrobial drugs. We also included trials comparing different doses, treatment durations, dosing frequencies, or routes of administration of antimicrobial agents. We excluded studies in which patients were not diagnosed according to internationally recommended criteria, or were not subjected to lower urinary tract segmented tests. DATA COLLECTION AND ANALYSIS: Study data were extracted independently by two review authors. Study outcomes were microbiological efficacy (pathogen eradication), clinical efficacy (symptom cure or improvement, or symptom scores) at test-of-cure visits or at follow-up, or both, and adverse effects of therapy. Secondary outcomes included microbiological recurrence rates.Statistical analysis was performed using a fixed-effect model for microbiological outcomes and a random-effects model for clinical outcomes and adverse effects. The results were expressed as risk ratios for dichotomous outcomes (with 95% confidence intervals) or as standardized mean differences for continuous or non-dichotomous variables. MAIN RESULTS: We identified 18 studies, enrolling a total of 2196 randomized patients. The oral fluoroquinolones ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin and prulifloxacin were compared. There were no significant differences in clinical or microbiological efficacy or in the rate of adverse effects between these fluoroquinolones. In chlamydial prostatitis, (i) azithromycin showed improved eradication rates and clinical cure rates compared to ciprofloxacin, with no significant differences regarding adverse effects; (ii) azithromycin was equivalent to clarithromycin, both microbiologically and clinically; (iii) prulifloxacin appeared to improve clinical symptoms, but not eradication rates, compared to doxycycline. In ureaplasmal prostatitis, the comparisons ofloxacin versus minocycline and azithromycin versus doxycycline showed similar microbiological, clinical and toxicity profiles. AUTHORS' CONCLUSIONS: The microbiological and clinical efficacy, as well as the adverse effect profile, of different oral fluoroquinolones are comparable. No conclusions can be drawn regarding the optimal treatment duration of fluoroquinolones in the treatment of CBP caused by traditional pathogens.Alternative antimicrobial agents tested for the treatment of CBP caused by traditional pathogens are co-trimoxazole, beta-lactams and tetracyclines, but no conclusive evidence can be drawn regarding the role of non-fluoroquinolone antibiotics in the treatment of CBP caused by traditional pathogens.In patients with CBP caused by obligate intracellular pathogens, macrolides showed higher microbiological and clinical cure rates compared to fluoroquinolones.

Chronic prostatitis and related psychological problems. Which came first: The chicken or the egg? A systematic review.

INTRODUCTION/AIM: A spectrum of psychological problems is commonly found in CP/CPPS patients, though it is not yet clear whether, a priori, psychological dysfunctions are the cause of these pain syndromes, or whether these pain conditions are themselves causing psychological disturbances. In this article we present the current perspective on the impact of psychological problems in chronic prostatitis syndromes and we discuss the implications thereof from a clinical perspective. MATERIALS AND METHODS: A database and a manual search were conducted in the MEDLINE database of the National Library of Medicine, EMBASE, and other libraries using the key words "prostatitis syndromes", "chronic bacterial prostatitis", "chronic pelvic pain", in various combinations with the terms "psychological issues", "depression" "anxiety", "stress", "unhappiness", "cognitive status" and "personality". Two independent reviewers performed data extraction. We included clinical studies with available information on chronic prostatitis and related psychological conditions. We considered full-text written papers. We excluded reviews and case reports. In order to reduce the risk of bias we analyzed only studies including patients with confirmed CBP or CP/CPPS. Bibliographic information in the selected publications was checked for relevant records not included in the initial search. RESULTS: Database search allowed us to retrieve 638 studies to which we added to 16 additional studies retrieved by hand-searching. After screening, 34 relevant papers were identified for thorough review. Most studies included patients with chronic pelvic pain and prostatitis-like symptoms, whereas a smaller number of studies included patients with methodologically con- firmed CP/CPPS including studies with a microbiologically confirmed diagnosis of CBP. The psychosocial factors examined in the selected studies include pain, catastrophizing, stress, personality factors and social aspects. Comorbid psychiatric disorders evidenced in the studies included depression, anxiety and trauma-related disorders, somatization disorders, and substance abuse. Some studies investigated the association of pain with each individual psychological disturbance, while others examined the impact of pain in association with the overall quality of life. Sample size, study design and diagnostic measures varied among studies. CONCLUSIONS: Despite limitations and variations in sample size, study design and diagnostic measures in all included studies, a relation between chronic prostatitis and psychological problems is a consistent finding. The existing evidence does not permit to definitely conclude whether psychological problems are a risk factor for CP/CPPS or whether they represent an array of symptoms that are associated with the exacerbation of this disease.

Treatment of urge incontinence in postmenopausal women: A systematic review.

BACKGROUND: Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. CONCLUSIONS: The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.

Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.

Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. CONCLUSIONS: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.

Safety considerations with new antibacterial approaches for chronic bacterial prostatitis.

INTRODUCTION: Chronic bacterial prostatitis (CBP) is a difficult-to-eradicate infection. Antibacterial therapy with currently licensed agents is hindered due to the increasing emergence of pathogen resistance worldwide and to frequent infection relapse. With limited treatment options, physicians are investigating new agents, which, however, may raise safety concerns. AREAS COVERED: Antibacterial agents currently licensed for CBP were not considered. Available reports about the safety and efficacy of antibacterial agents that have been clinically tested or tentatively used to treat CBP in single cases were evaluated. This review also focused on agents targeting Gram-positive pathogens, whose prevalence as causative agents of CBP is increasing. EXPERT OPINION: (i) Most antibacterial agents considered in this review have been administered off-label in the interest of patients, and their use requires particular caution. (ii) Reports describing the usage of many of the drugs reviewed here are still scant, and readers should be warned of the limited published evidence supporting therapy for CBP with these agents. (iii) As treatment must extend over several weeks, medium-term adverse events may occur and therapy should be individualized, taking into account the dosage and the potential toxicity of each specific antibiotic. Regarding dangerous drug-drug interactions, particular attention should be paid to the risk of ECG-QT-interval elongation.

Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis.

OBJECTIVE: Proton pump inhibitors are widely used as treatment of acid-related disorders. They are considered safe although their long-term use has been associated with some adverse effects including an increased propensity for urinary calculi formation. The aim of this study was to systematically review available data from studies evaluating the association of PPIs and nephrolithiasis. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for cohort studies or case-control studies evaluating the relationship between treatment with proton pump inhibitors and the risk of stone formation published up to 31 October 2022. The overall association of PPIs and urinary calculi was analyzed using a random effects model (RevMan5). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: A total of 550 studies were retrieved; 7 were selected by title and abstract screening; after removal of duplicates, 4 records were evaluated by full-text examination. An additional study was retrieved by handsearching the references included in screened studies. In the unadjusted analysis, the odds of urinary calculi were greater in subjects taking PPIs compared to controls (unadjusted OR = 2.10, 95% CI 1.74-2.52, p < 0.00001). The pooled odds ratio of two case-control studies confirmed that use of PPIs increased the odds of urinary calculi compared with non-use (OR 2.44, 95% CI 2.29 to 2.61). Pooled analysis of three cohort studies evaluating incident nephrolithiasis showed an overall hazard ratio estimate of 1.34 (95% CI = 1.28-1.40). One study found lower urinary citrate and urinary magnesium levels in subjects exposed to PPIs. The Newcastle-Ottawa Quality Assessment Scale scores ranged between 6 and 8. CONCLUSIONS: PPIs showed an association with urinary calculi in patients included in the studies included in this review. If these data will be confirmed in adequately powered randomized trials, clinicians may consider limiting the long-term use of PPIs, to avoid unnecessary prolongation of treatment. Urinary magnesium and citrate should be evaluated in renal stone forming patients taking PPIs to supplement their intake when requested.

Efficacy of overactive neurogenic bladder treatment: A systematic review of randomized controlled trials.

BACKGROUND: Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke. OBJECTIVE: The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022. RESULTS: A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups. CONCLUSIONS: The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.