The impact of obesity and sexual behavior on prostate cancer risk is mediated by testosterone levels: a mendelian randomization study and mediation analysis.

Background: The relationship between obesity, sexual behavior, and prostate cancer (PCa) has been widely debated, contributing to a lack of understanding of its potential mechanisms and hindering the development of effective prevention measures. Purpose: The aim of this study was to examine the causal effect of body mass index (BMI), age at first sexual intercourse (AFS), and bioavailable testosterone levels on PCa while also quantifying the potential roles of mediators. Method: We conducted a Mendelian randomization (MR) study using summary statistics from genome-wide associations of BMI (152,893 European males), AFS (182,791 European males), bioavailable testosterone (184,205 European males), and PCa (79,148 cases, 61,106 controls, European ancestry). Inverse-variance weighted method, weighted median method, MR-Egger regression, Least Absolute Shrinkage and Selection Operator (LASSO), and outlier test were used for MR analyses. Reverse MR and mediation analysis were performed. Data analyses were conducted from December 2022 to July 2023. Results: The results showed that genetic liability to BMI was protective of PCa (OR, 0.82; 95% CI: 0.74-0.91; P = 3.29 × 10-4). Genetic liability to later AFS (OR, 1.28; 95% CI: 1.08-1.53; P = 5.64 × 10-3) and higher bioavailable testosterone levels (OR = 1.11, 95% CI: 1.01-1.24, P = 0.04) were associated with an increased risk of PCa. All of these potential causal effects could only be forwarded and were not affected by prostate specific antigen (PSA) screening. After controlling for bioavailable testosterone levels, the causal impact of BMI and AFS on PCa was no longer significant. The mediation analysis suggested that the causal influence of AFS/BMI on PCa relied on bioavailable testosterone levels. Conclusion: In conclusion, the difference between the univariable and multivariable MR results suggested that the causal influence of BMI and AFS on PCa relied on bioavailable testosterone levels. Further work is needed to identify other risk factors and to elucidate the specific mechanisms that underlie this causal pathway.

Vasectomy and risk of prostate cancer: A Mendelian randomization study and confounder analysis.

BACKGROUND: Previous reports have shown a potential causal impact of vasectomy on prostate cancer (PCa). The objective of this study was to investigate the association between vasectomy and PCa, while evaluating the influence of confounding factors such as prostate-specific antigen (PSA) screening and body mass index (BMI). METHODS: Mendelian randomization (MR) study using summary statistics from genome-wide associations of vasectomy (462,933 European ancestry), ever had PSA test (200,410 European ancestry), time since last PSA test (46,104 European ancestry), BMI (152,893 European males) and PCa (79,148 cases, 61,106 controls, European ancestry). This study was conducted using summary statistic data from large, previously described cohorts. Data analyses were conducted from November 2022 to June 2023. RESULTS: Genetic liability to vasectomy was not associated with PCa (OR = 0.07, 95% CI: 2.95 × 10-3 , 1.54, p = 0.09). Genetic liability to vasectomy was not associated with ever had PSA test (OR = 1.08, 95% CI: 0.49-2.39, p = 0.83) and time since last PSA test (OR = 2.49, 95% CI: 0.71-8.79, p = 0.16). After controlling for PSA test and BMI, there remains no causal relationship between vasectomy and PCa risk (OR = 5.56 × 10-4 , 95% CI: 7.29 × 10-8 , 4.24, p = 0.10). The reverse MR results showed a weak association between PCa and vasectomy patients (OR = 1.00, 95% CI: 1.0003-1.0033, p = 0.02). CONCLUSION: Based on the available evidence from MR analysis, the current findings did not support vasectomy being a risk factor for PCa. Further work is required to provide additional confirmation and validation of the potential link.

Preoperative hormone therapy in single-stage repair of hypospadias: A comprehensive systematic review.

INTRODUCTION: Preoperative hormone therapy (PHT) holds promise for obtaining better surgical conditions for patients undergoing hypospadias correction and increasing the success rate. However, the application and effects of PHT remain uncertain owing to a lack of comprehensive evaluation, thus limiting treatment strategies and development of standardized guidelines. This study aimed to review the following (ⅰ) the criteria and regimens of PHT (ⅱ) its impact on penile growth, postoperative complications, and side effects (ⅲ) and sources of inconsistent clinical outcomes. METHODS: This systematic review was registered at PROSPERO (CRD42022346924) and conducted and reported following international recommendations, including the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We searched the databases over the last two decades to identify eligible studies. This systematic review included literature regarding the use of PHT in the treatment of children with single stage hypospadias repair. Risk of Bias (RoB) was measured using two different tools: randomized controlled trials using a modified version of the RoB Assessment Tool and non-randomized studies of interventions using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). The R-3.6.3 software was used for the analysis. RESULTS: In total, 25 studies involving 4094 patients were included in the systematic review. The surgeons' criteria for using PHT varied, with short penile length being the most important. The most frequently reported regimens for intramuscular (IM) testosterone were either 2 mg/kg or empiric 25 mg monthly, and the duration was 2-3 months preoperatively. Androgens were significantly effective in improving penile development, and the changes commonly peaked at 2-3 months. The effects of PHT on complications and side effects are controversial, and the potential causes include hormone sensitivity, degree of hypospadias, surgical techniques, and dosing regimens. CONCLUSIONS: This systematic review evaluated PHT in children with hypospadias. Building on previous studies, this review provides a more specific attitude and possible aspects for resolving the controversies. Future studies should identify the applicable subgroups of patients and standardize the dose and mode of delivery for the best clinical results.