Serenoa repens and its effects on male sexual function. A systematic review and meta-analysis of clinical trials

Background: Serenoa repens (SR) is a plant used to treat benign prostatic hyperplasia and prostatitis. We know that SR act as a 5\u3b1-reductase inhibitor, moreover, several studies have proved that SR has anti-inflammatory and antioxidant properties. There is some belief among patients that SR may negatively impact male sexual function. Such belief is circulating in non-medical social networks and is perhaps maintained by patients as a result of incorrect web surfing. However, it is also possible that SR may exert a "nocebo" effect thus negatively impacting on the general well-being of patients. Objective: The aim of this study is to investigate whether SR is causing negative effects on male sexual function. Methods: To ascertain the effect of SR on male sexual function, we conducted a systematic review and meta-analysis, by performing an electronic database search in accordance with the PRISMA guidelines. Results: Out of 20 included papers, 8 papers reported comparisons of SR with placebo, and 7 studies reported comparisons of SR with tamsulosin. The standardized mean difference of changes from baseline scores of sexual function was not significantly different between SR and placebo (SMD: 0.43, 95% CI: 0.18 to 1.05; I^2 = 95%). Similarly, no significant mean differences in the Male Sexual Function-4 (MSF-4) test scores were found between SR and tamsulosin (SMD: -0.31, 95% CI: -0.82 to 0.19; I^2 = 90%). Conclusions: We found no statistically significant differences between negative effects on sexual function in patients treated with SR compared to patients who received placebo. The results of our meta-analysis are similar to those of other systematic reviews. Studies are warranted to ascertain whether any such effects might occur as a result of a nocebo effect

Influence of infection on the distribution patterns of NIH-Chronic Prostatitis Symptom Index scores in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition for which the etiological determinants are still poorly defined. To better characterize the diagnostic and therapeutic profile of patients, an algorithm known as UPOINT was created, addressing six major phenotypic domains of CP/CPPS, specifically the urinary (U), psycho-social (P), organ-specific (O), infection (I), neurological/systemic (N) and muscular tenderness (T) domains. An additional sexual dysfunction domain may be included in the UPOINT(S) system. The impact of the infection domain on the severity of CP/CPPS symptoms is a controversial issue, due to the contradictory results of different trials. The aim of the present retrospective study was to further analyze the extent to which a positive infection domain of UPOINTS may modify the pattern of CP/CPPS symptom scores, assessed with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). In a cohort of 935 patients that was divided on the basis of the presence or absence of prostatic infection, more severe clinical symptoms were shown by the patients with infection (median NIH total score: 24 versus 20 points in uninfected patients; P<0.001). Moreover, NIH-CPSI score distribution curves were shifted towards more severe symptoms in patients with a positive infection domain. Division of the patients into the six most prominent phenotypic clusters of UPOINTS revealed that the 'prostate infection-related sexual dysfunction' cluster, including the highest proportion of patients with evidence of infection (80%), scored the highest number of NIH-CPSI points among all the clusters. To assess the influence of the infection domain on the severity of patients' symptoms, all subjects with evidence of infection were withdrawn from the 'prostate infection-related sexual dysfunction' cluster. This modified cluster showed symptom scores significantly less severe than the original cluster, and the CPSI values became comparable to the scores of the five other clusters, which were virtually devoid of patients with evidence of infection. These results suggest that the presence of pathogens in the prostate gland may significantly affect the clinical presentation of patients affected by CP/CPPS, and that the infection domain may be a determinant of the severity of CP/CPPS symptoms in clusters of patients phenotyped with the UPOINTS system. This evidence may convey considerable therapeutic implications

Drug-induced gynecomastia: A systematic review and meta-analysis of randomized clinical trials

Objective: To review the evidence concerning treatment-related gynecomastia in patients taking spironolactone, antiandrogens, 5 alpha-reductase inhibitors, lipid-lowering and psychotropic drugs. Material and methods: A search of Medline and EMBASE was performed up to 30 June 2021. We included randomized controlled trials comparing the effects of a drug belonging to these classes versus placebo or versus a drug of the same class. Results: A total of 32 randomized controlled trials were included in the final review. There was an increased odds of gynecomastia in men receiving antiandrogens (OR = 17.38, 95% CI: 11.26 to 26.82; 6 trials, 9599 participants) and 5 alpha-reductase inhibitors compared to controls (OR = 1.77, 95% CI: 1.53 to 2.06; 7 series out of 6 trials, 34860 participants). The use of spironolactone in mixed gender populations was characterized by significantly higher odds of having gynecomastia compared to controls (OR = 8.39, 95% CI: 5.03 to 13.99; 14 trials, 3745 participants). No placebo-controlled trials focusing on the risk of gynecomastia in patients taking antipsychotic drugs was available, although there was a significant difference in the odds of having gynecomastia in a comparison between risperidone and quetiapine (OR = 4.32, 95% CI: 1.31 to 14.27; 3 trials, 343 participants). Limited evidence about the effects of statins on mammary glands was found. Conclusions: Antiandrogens and to a lesser extent 5 alphareductase inhibitors and spironolactone are associated with an increased risk of developing gynecomastia. Such effect can be explained by a modification of the testosterone to estradiol ratio. Gynecomastia (and galactorrhea) associated to the use of conventional and certain atypical antipsychotics can be related to high prolactin levels

The radiosensitizing effect of Ku70/80 knockdown in MCF10A cells irradiated with X-rays and p(66)+Be(40) neutrons

Background: A better understanding of the underlying mechanisms of DNA repair after low-and high-LET radiations represents a research priority aimed at improving the outcome of clinical radiotherapy. To date however, our knowledge regarding the importance of DNA DSB repair proteins and mechanisms in the response of human cells to high-LET radiation, is far from being complete. Methods: We investigated the radiosensitizing effect after interfering with the DNA repair capacity in a human mammary epithelial cell line (MCF10A) by lentiviral-mediated RNA interference (RNAi) of the Ku70 protein, a key-element of the non-homologous end-joining (NHEJ) pathway. Following irradiation of control and Ku-deficient cell lines with either 6 MV X-rays or p(66)+Be(40) neutrons, cellular radiosensitivity testing was performed using a crystal violet cell proliferation assay. Chromosomal radiosensitivity was evaluated using the micronucleus (MN) assay. Results: RNAi of Ku70 caused downregulation of both the Ku70 and the Ku80 proteins. This downregulation sensitized cells to both X-rays and neutrons. Comparable dose modifying factors (DMFs) for X-rays and neutrons of 1.62 and 1.52 respectively were obtained with the cell proliferation assay, which points to the similar involvement of the Ku heterodimer in the cellular response to both types of radiation beams. After using the MN assay to evaluate chromosomal radiosensitivity, the obtained DMFs for X-ray doses of 2 and 4 Gy were 2.95 and 2.66 respectively. After neutron irradiation, the DMFs for doses of 1 and 2 Gy were 3.36 and 2.82 respectively. The fact that DMFs are in the same range for X-rays and neutrons confirms a similar importance of the NHEJ pathway and the Ku heterodimer for repairing DNA damage induced by both X-rays and p(66)+Be(40) neutrons. Conclusions: Interfering with the NHEJ pathway enhanced the radiosensitivity of human MCF10A cells to low-LET Xrays and high-LET neutrons, pointing to the importance of the Ku heterodimer for repairing damage induced by both types of radiation. Further research using other high-LET radiation sources is however needed to unravel the involvement of DNA double strand break repair pathways and proteins in the cellular response of human cells to high-LET radiation

Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay

Breast cancer risk drastically increases in individuals with a heterozygous germline BRCA1 or BRCA2 mutation, while it is estimated to equal the population risk for relatives without the familial mutation (non-carriers). The aim of the present study was to use a G2 phase-specific micronucleus assay to investigate whether lymphocytes of healthy BRCA2 mutation carriers are characterized by increased radiosensitivity compared to controls without a family history of breast/ovarian cancer and how this relates to healthy non-carrier relatives. BRCA2 is active in homologous recombination, a DNA damage repair pathway, specifically active in the late S/G2 phase of the cell cycle. We found a significantly increased radiosensitivity in a cohort of healthy BRCA2 mutation carriers compared to individuals without a familial history of breast cancer (P=0.046; Mann-Whitney U test). At the individual level, 50% of healthy BRCA2 mutation carriers showed a radiosensitive phenotype (radiosensitivity score of 1 or 2), whereas 83% of the controls showed no radiosensitivity (P=0.038; one-tailed Fisher's exact test). An odds ratio of 5 (95% CI, 1.07-23.47) indicated an association between the BRCA2 mutation and radiosensitivity in healthy mutation carriers. These results indicate the need for the gentle use of ionizing radiation for either diagnostic or therapeutic use in BRCA2 mutation carriers. We detected no increased radiosensitivity in the non-carrier relatives

Prevention and modulation of aminoglycoside ototoxicity (Review)

More than 60 years after their isolation and characterization, aminoglycoside (AG) antibiotics remain powerful agents in the treatment of severe gram-negative, enterococcal or mycobacterial infections. However, the clinical use of AGs is hampered by nephrotoxicity and ototoxicity, which often develop as a consequence of prolonged courses of therapy, or of administration of increased doses of these drugs. The discovery of non-ototoxic antibacterial agents, showing a wider spectrum of activity, has gradually decreased the use of AGs as first line antibiotics for many systemic infections. However, AGs are now undergoing an unexpected revival, being increasingly indicated for the treatment of severe emerging infections caused by organisms showing resistance to most first-line agents (e.g., multidrug-resistant tuberculosis, complicated nosocomially-acquired acute urinary tract infections). Increasing adoption of aminoglycosides poses again to scientists and physicians the problem of toxicity directed to the kidneys and to the inner ear. In particular, aminoglycoside-induced deafness can be profound and irreversible, especially in genetically predisposed patients. For this reason, an impressive amount of molecular strategies have been developed in the last decade to counteract the ototoxic effect of aminoglycosides. The present article overviews: i) the molecular mechanisms by which aminoglycosides exert their bactericidal activity, ii) the mechanisms whereby AGs exert their ototoxic activity in genetically-predisposed patients, iii) the drugs and compounds that have so far proven to prevent or modulate AG ototoxicity at the preclinical and/or clinical level, and iv) the dosage regimens that have so far been suggested to decrease the incidence of episodes of AG-induced ototoxicity

Chlamydia trachomatis versus common uropathogens as a cause of chronic bacterial prostatitis: Is there any difference? Results of a prospective parallel-cohort study

Purpose: The role of Chlamydia trachomatis (CT) infection in chronic bacterial prostatitis (CBP) is well known. What is unclear is whether there are any differences in the course or clinical outcome of the disease when the cause is CT or other uropathogens. Materials and Methods: A series of 311 patients affected by CBP due to CT (cohort A) was compared with a group of 524 patients affected by CBP caused by common uropathogen bacteria (cohort B). All participants completed the following questionnaires: National Institutes of Health Chronic Prostatitis Symptom Index, International Prostate Symptom Score, International Index of Erectile Function-15 erectile function domain (IIEF-15-EFD), Premature Ejaculation Diagnostic Tool (PEDT), and the Short Form 36 (SF-36) Health Survey. All patients were followed with clinical and microbiological evaluations. Results: After a mean follow-up time of 42.3 months, the number of symptomatic episodes was significantly higher in patients in cohort A than in cohort B (4.1±1.1 vs. 2.8±0.8, p<0.001), and the mean time to first symptomatic recurrence was shorter in cohort A than in cohort B (3.3±2.3 months vs. 5.7±1.9 months, p<0.001). Moreover, scores on the SF-36 tool were significantly lower in cohort A (96.5±1.0 vs. 99.7±1.9, p<0.001) at the first symptomatic recurrence. Cohort A also showed significantly lower scores on the IIEF-15-EFD and PEDT questionnaires at the end of the follow-up period (26.8±2.9 vs. 27.3±3.3, p=0.02 and 11.5±2.3 vs. 4.5±2.8, p<0.001, respectively). Conclusions: Patients affected by CBP due to CT infection have a higher number of symptomatic recurrences with a more severe impact on quality of life

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

A Switch Therapy Protocol with Intravenous Azithromycin and Ciprofloxacin Combination for Severe, Relapsing Chronic Bacterial Prostatitis: a Prospective Non-comparative Pilot Study

Chronic bacterial prostatitis (CBP) is characterized by intense clinical symptoms, frequent relapse episodes and poor quality of life. Aggressive antibacterial therapy is warranted to eradicate causative pathogens and to achieve a permanent cure. We administered a “switch-therapy” protocol to 30 patients showing severe CBP symptoms and two or more relapse episodes in the previous 12 months. Patients received intravenous azithromycin (500 mg/day) and ciprofloxacin (800 mg/day) for three days, followed by oral ciprofloxacin (1 g/day) for 25 days. Twenty-seven (90%) patients showed pathogen eradication at test-of-cure (TOC) visit. Five cases of infection relapse were detected at follow-up. At the TOC visit, 25 patients (83%) showed mild/absent symptoms, measured with the NIH-chronic prostatitis symptom index. These results indicate the efficacy of a “switch-therapy” protocol, based on combined azithromycin and ciprofloxacin. Comparative studies on larger CBP patient populations are warranted to confirm these encouraging results

Infectious complications of endourological treatment of kidney stones: A meta-analysis of randomized clinical trials

Objective: Endourological treatment is associated with a risk of postoperative febrile urinary tract infections and sepsis. The aim of this study was to review the reported rate of infectious complications in relation to the type and modality of the endourologic procedure. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. Two electronic databases (PubMed and EMBASE) were searched. Out of 243 articles retrieved we included 49 studies after full-text evaluation. Results: Random-effects meta-analysis demonstrated that retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) were associated with not significantly different odds of getting fever (OR = 1.54, 95% CI: 0.99 to 2.39; p = 0.06) or sepsis (OR = 1.52, 95% CI: 0.37 to 6.20, p = 0.56). The odds of getting fever were not significantly different for mini PCNL compared to standard PCNL (OR = 1.11, 95% CI: 0.85 to 1.44; p = 0.45) and for tubeless PCNL compared to standard PCNL (OR = 1.34 95% CI: 0.61 to 2.91, p = 0.47). However, the odds for fever after PCNL with suctioning sheath were lower than the corresponding odds for standard PCNL (OR = 0.37, 95% CI: 0.20 to 0.70, p = 0.002). The odds of getting fever after PCNL with perioperative prophylaxis were not different from the corresponding odds after PCNL with perioperative prophylaxis plus a short oral antibiotic course (before or after the procedure) (OR = 1.31, 95% CI: 0.71 to 2.39, p = 0.38). Conclusions: The type of endourological procedure does not appear to be decisive in the onset of infectious complications, although the prevention of high intrarenal pressure during the procedure could be crucial in defining the risk of infectious complications. on behalf of U-merge Ltd. (Urology for emerging countries), London-Athens-Duba