Use of 5-alpha reductase inhibitors and risk of gastrointestinal cancers in men with benign prostatic hyperplasia: A population-based cohort study.

Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia.

A prospective, randomized, open-label, parallel trial comparing the efficacy of α-blocker or 5α-reductase inhibitor withdrawal to continued combination therapy on the maintenance of lower urinary tract symptoms in men with benign prostatic hyperplasia.

BACKGROUND: It is uncertain how long combination therapy should be continued in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). We investigated the withdrawal effects of α1-adrenergic receptor blocker (AB) or 5α-reductase inhibitor (5ARI) following successful combination therapy. METHODS: This prospective, randomized, open-label, parallel trial enrolled 222 patients with BPH/LUTS who showed at least a seven-point improvement in International Prostate Symptom Score-total (IPSS-T) and a ≥ 20% reduction in prostate volume (PV) following the initiation of combination therapy. Patients were randomized in a 1:1:1 ratio into continued-combination, AB-withdrawal, and 5ARI-withdrawal groups. IPSS, overactive bladder symptom score, EuroQol-five-dimensional questionnaire (EQ-5D-5L), EuroQol-visual analog scale (EQ-VAS), prostate volume (PV), maximal flow rate, postvoid residual urine (PVR), and prostate-specific antigen level were assessed every 6 months for 24 months. The predictors of IPSS-T deterioration were evaluated. RESULTS: At Month 24, IPSS-T deterioration (≥2 point) was observed in 20/72 (27.8%) and 19/72 (26.4%) patients in the AB- and 5ARI-withdrawal groups, respectively. Among them, 4/72 (5.6%) and 4/70 (5.7%) patients required readdition of the withdrawn drug (p = 0.868). In the continued combination group, EQ-VAS improved at Month 24 compared to baseline (p = 0.028). At Month 24, the AB-withdrawal group showed improvements in EQ-5D-5L, EQ-VAS, and PVR (all p < 0.005), while the 5ARI-withdrawal group showed improvement in IPSS-S (p = 0.011). Diabetes mellitus was associated with IPSS-T deterioration at Month 24 (p = 0.020). CONCLUSIONS: In patients with BPH/LUTS who are reluctant to continue combination therapy, AB or 5ARI withdrawal may be offered in men with improvement in IPSS-T by at least seven points and reduction in PV by at least 20%.

Emerging drugs for the treatment of benign prostatic hyperplasia: a 2023 update.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a condition that affects over 50% of men as they enter their fifth decade of life, often leading to lower urinary tract symptoms (LUTS). Primary treatment options include alpha blockers, 5-alpha reductase inhibitors, and phosphodiesterase-5 inhibitors. However, these medications can have some side effects, and there is a noticeable dearth of information addressing the long-term use of these medications. Thus, the exploration of all treatment modalities helps ensure patients receive personalized and effective care. Consequently, the primary objective of this review is to identify potential emerging medications for the treatment of BPH. AREAS COVERED: We conducted an extensive review of articles discussing pharmacotherapy for BPH spanning the last 15 years. Our information gathering process involved Scopus, PubMed-MEDLINE, Cochrane, Wiley Online Library Google Scholar, ClinicalTrials.gov, and the PharmaProjects database. This approach ensures that readers gain an in-depth knowledge of the existing therapeutic agents as well as promising avenues for managing BPH. EXPERT OPINION: BPH treatment targets a patient's specific constellation of symptoms. Therefore, a broad knowledge base encompassing various treatment options is paramount in ensuring optimal treatment. Looking forward, the emphasis on personalization promises to reshape the landscape of BPH treatment and improve patient outcomes.

External validation of the barcelona magnetic resonance imaging predictive model for detecting significant prostate cancer including men receiving 5-alpha reductase inhibitors.

PURPOSE: To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). MATERIALS AND METHODS: A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2. RESULTS: The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783-0.842) and 0.849 (0.806-0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users. CONCLUSIONS: The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.

Analysis of the finasteride treatment and its withdrawal in the rat hypothalamus and hippocampus at whole-transcriptome level.

PURPOSE: As reported in patients treated for androgenetic alopecia with finasteride (i.e., a blocker of the enzyme 5 alpha-reductase) and in an animal model, side effects affecting sexual, psychiatric, neurological, and physical domains, may occur during the treatment and persist with drug suspension. The etiopathogenesis of these side effects has been poorly explored. Therefore, we performed a genome-wide analysis of finasteride effects in the brain of adult male rat. METHODS: Animals were treated (i.e., for 20 days) with finasteride (1mg/rat/day). 24 h after the last treatment and 1 month after drug suspension, RNA sequencing analysis was performed in hypothalamus and hippocampus. Data were analyzed by differential expression analysis and Gene-Set Enrichment Analyses (GSEA). RESULTS: Data obtained after finasteride treatment showed that 186 genes (i.e., 171 up- and 15 downregulated) and 19 (i.e., 17 up- and 2 downregulated) were differentially expressed in the hypothalamus and hippocampus, respectively. Differential expression analysis at the drug withdrawal failed to identify dysregulated genes. Several gene-sets were enriched in these brain areas at both time points. CONCLUSION: Some of the genes reported to be differentially expressed (i.e., TTR, DIO2, CLDN1, CLDN2, SLC4A5, KCNE2, CROT, HCRT, MARCKSL1, VGF, IRF2BPL) and GSEA, suggest a potential link with specific side effects previously observed in patients and in the animal model, such as depression, anxiety, disturbance in memory and attention, and sleep disturbance. These data may provide an important background for future experiments aimed at confirming the pathological role of these genes.

Medical Advancements in Benign Prostatic Hyperplasia Treatments.

PURPOSE OF REVIEW: This review aims to identify and summarize the current literature on the most recent therapeutic agents and combination strategies for the medical management of lower urinary tract symptoms resulting from benign prostatic hyperplasia. RECENT FINDINGS: The latest advancements in BPH therapy have been in combination strategies. Alpha blockers continue to be the mainstay of treatment, but research is exploring the synergistic benefits of combining them with 5-alpha reductase inhibitors (5-ARIs), phosphodiesterase-5 (PDE5) inhibitors, and beta-3 agonists. The alpha-blocker + 5-ARI combination remains ideal for enlarged, significantly reducing clinical progression risk compared to monotherapy. Alpha-blocker + PDE5 inhibitor combinations appear safe and potentially beneficial for men with concomitant erectile dysfunction; sildenafil might hold an edge over tadalafil based on limited data. Beta-3 agonists show synergistic effects with alpha blockers for residual storage symptoms, offering similar efficacy to anticholinergics but with a better side effect profile.

Management of androgenic alopecia: a systematic review of the literature.

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

Adverse effects of the 5-alpha-reductase inhibitor finasteride on Daphnia magna: Endocrine system and lipid metabolism disruption.

Finasteride, a steroid 5-alpha reductase inhibitor, is commonly used for the treatment of benign prostatic hyperplasia and hair loss. However, despite continued use, its environmental implications have not been thoroughly investigated. Thus, we investigated the acute and chronic adverse impacts of finasteride on Daphnia magna, a crucial planktonic crustacean in freshwater ecosystems selected as bioindicator organism for understanding the ecotoxicological effects. Chronic exposure (for 23 days) to finasteride negatively affected development and reproduction, leading to reduced fecundity, delayed first brood, reduced growth, and reduced neonate size. Additionally, acute exposure (< 24 h) caused decreased expression levels of genes crucial for reproduction and development, especially EcR-A/B (ecdysone receptors), Jhe (juvenile hormone esterase), and Vtg2 (vitellogenin), with oxidative stress-related genes. Untargeted lipidomics/metabolomic analyses revealed lipidomic alteration, including 19 upregulated and 4 downregulated enriched lipid ontology categories, and confirmed downregulation of metabolites. Pathway analysis implicated significant effects on metabolic pathways, including the pentose phosphate pathway, histidine metabolism, beta-alanine metabolism, as well as alanine, aspartate, and glutamate metabolism. This comprehensive study unravels the intricate molecular and metabolic responses of D. magna to finasteride exposure, underscoring the multifaceted impacts of this anti-androgenic compound on a keystone species of freshwater ecosystems. The findings emphasize the importance of understanding the environmental repercussions of widely used pharmaceuticals to protect biodiversity in aquatic ecosystems.

Do statins decrease testosterone in men? Systematic review and meta-analysis.

PURPOSE: Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones. MATERIALS AND METHODS: Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool. RESULTS: There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001).In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal. CONCLUSION: Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.

Long-term risk of benign prostatic hyperplasia-related surgery and acute urinary retention in men treated with 5-alpha reductase inhibitor versus alpha-blocker monotherapy in routine clinical care.

OBJECTIVES: To assess the risk of benign prostatic hyperplasia (BPH)-related surgery and acute urinary retention (AUR) in men treated with 5-alpha-reductase inhibitor (5-ARI) versus alpha-blocker monotherapy in routine clinical care over 15 years of follow-up. METHODS: Using population-based Danish Health registries, we identified all new-users of 5-ARI or alpha-blocker monotherapy in Denmark, 1997-2017. We defined an index date 180 days after the date of first prescription and included men who redeemed at least one additional prescription before the index date. We used multiple imputation to replace missing prostate-specific antigen values. We performed propensity score-weighted Cox regression to estimate weighted hazard ratios (wHRs) and cumulative incidence function to estimate weighted cumulative risks of BPH-related surgery and AUR in intention to treat (ITT) and per protocol (PP) analyses. RESULTS: We included 18,421 and 95,984 men treated with 5-ARI and alpha-blocker monotherapy, respectively. Overall, treatment with 5-ARI monotherapy was associated with a reduced risk of BPH-related surgery (ITT wHR = 0.73 (95% confidence interval [CI]: 0.68-0.78), PP wHR = 0.77 (95% CI: 0.70-0.84) and AUR (ITT wHR = 0.73 (95% CI: 0.67-0.78), PP wHR = 0.75 (95% CI: 0.66-0.84). The 15-year risk of BPH-related surgery in men treated with 5-ARI versus alpha-blocker monotherapy was 14.8% (95% CI: 14.1%-15.5%) versus 19.1% (95% CI: 18.7%-19.5%) in the ITT analysis and 13.8% (95% CI: 12.6%-14.9%) versus 17.5% (95% CI: 16.9%-18.0%) in the PP analysis. The 15-year risk of AUR in men treated with 5-ARI versus alpha-blocker was 13.0% (95% CI: 12.3%-13.6%) versus 16.6% (95% CI: 16.3%-17.0%) in the ITT analysis and 12.6% (95%: 11.3%-14.0%) versus 16.9% (95% CI: 16.3%-17.6%) in the PP analysis. CONCLUSION: Treatment with 5-ARI versus alpha-blocker monotherapy in routine clinical care was associated with a reduced risk of BPH-related surgery and AUR for up to 15 years of follow-up. After 15 years of follow-up, the relative risk reduction was 21%-25% and the absolute risk reduction was 4%.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.

BACKGROUND: Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. METHODS: Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. RESULTS: In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2 yr) and longer-term (> 2 yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). CONCLUSIONS: We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.

Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study.

BACKGROUND: We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. METHODS: This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. RESULTS: Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). CONCLUSION: This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.

Development of a machine learning-based predictive model for prediction of success or failure of medical management for benign prostatic hyperplasia.

OBJECTIVE: To develop a novel predictive model for identifying patients who will and will not respond to the medical management of benign prostatic hyperplasia (BPH). METHODS: Using data from the Medical Therapy of Prostatic Symptoms (MTOPS) study, several models were constructed using an initial data set of 2172 patients with BPH who were treated with doxazosin (Group 1), finasteride (Group 2), and combination therapy (Group 3). K-fold stratified cross-validation was performed on each group, Within each group, feature selection and dimensionality reduction using nonnegative matrix factorization (NMF) were performed based on the training data, before several machine learning algorithms were tested; the most accurate models, boosted support vector machines (SVMs), being selected for further refinement. The area under the receiver operating curve (AUC) was calculated and used to determine the optimal operating points. Patients were classified as treatment failures or responders, based on whether they fell below or above the AUC threshold for each group and for the whole data set. RESULTS: For the entire cohort, the AUC for the boosted SVM model was 0.698. For patients in Group 1, the AUC was 0.729, for Group 2, the AUC was 0.719, and for Group 3, the AUC was 0.698. CONCLUSION: Using MTOPS data, we were able to develop a prediction model with an acceptable rate of discrimination of medical management success for BPH.

5-alpha reductase inhibitors and MRI prostates: actively reducing prostate sizes and ambiguity.

BACKGROUND: Magnetic resonance imaging (MRI) scans are increasingly first-line investigations for suspected prostate cancer, and essential in the decision for biopsy. 5-alpha reductase inhibitor (5-ARI) use has been shown to reduce prostate size and prostate cancer risk. However, insufficient data exists on how 5-ARI use affects MRI findings and yield of biopsy. This study explores the differences in imaging and prostate cancer diagnoses between patients receiving and not receiving 5-ARI therapy. METHODS: From 2015 to 2020, we collected retrospective data of consecutive patients undergoing prostate biopsy at one centre. We included patients who were biopsy-naïve, had prior negative biopsies, or on active surveillance for low-grade prostate cancer. Clinical and pathological data was collected, including 5-ARI use, Prostate Imaging Reporting and Data System (PIRADS) classification and biopsy results. RESULTS: 351 men underwent saturation biopsy with or without targeted biopsies. 54 (15.3%) had a history of 5-ARI use. On mpMRI, there was no significant difference between the 5ARI and non-5-ARI groups in PIRADS distribution, number of lesions, and lesion location. Significantly fewer cancers were detected in the 5-ARI group (46.3% vs. 68.0%; p < 0.01). There were no significant differences in PIRADS distribution in 5-ARI patients with positive and negative biopsy. CONCLUSION: Our study found significant differences in biochemical, imaging and biopsy characteristics between 5-ARI and non-5-ARI groups. While both groups had similar PIRADS distribution, 5-ARI patients had a lower rate of positive biopsies across all PIRADS categories, which may suggest that the use of 5ARI may confound MRI findings. Further studies on how 5-ARI therapy affects the imaging characteristics of prostate cancer should be performed.

Exploring the Enigma of 5-ARIs Resistance in Benign Prostatic Hyperplasia: Paving the Path for Personalized Medicine.

PURPOSE OF REVIEW: Despite the widespread utilization of 5-alpha reductase inhibitors (5-ARIs) for managing benign prostatic hyperplasia (BPH), certain BPH patients exhibit unresponsiveness to 5-ARIs therapy. This paper provides a comprehensive overview of the current perspectives on the mechanisms of 5-ARIs resistance in BPH patients and integrates potential biomarkers and underlying therapeutic options for 5-ARIs resistance. These findings may facilitate the development of novel or optimize more effective treatment options, and promote personalized medicine for BPH. RECENT FINDINGS: The pathways contributing to resistance against 5-ARIs in certain BPH patients encompass epigenetic modifications, shifts in hormone levels, autophagic processes, and variations in androgen receptor structures, and these pathways may ultimately be attributed to inflammation. Promisingly, novel biomarkers, including intravesical prostatic protrusion, inflammatory factors, and single nucleotide polymorphisms, may offer predictive insights into the responsiveness to 5-ARIs therapy, empowering physicians to fine-tune treatment strategies. Additionally, on the horizon, GV1001 and mTOR inhibitors have emerged as potential alternative therapeutic modalities for addressing BPH in the future. After extensive investigation into BPH's pathological processes and molecular landscape, it is now recognized that diverse pathophysiological mechanisms may contribute to different BPH subtypes among individuals. This insight necessitates the adoption of personalized treatment strategies, moving beyond the prevailing one-size-fits-all paradigm centered around 5-ARIs. The imperative for early identification of individuals prone to treatment resistance will drive physicians to proactively stratify risk and adapt treatment tactics in future practice. This personalized medicine approach marks a progression from the current standard treatment model, emerging as the future trajectory in BPH management.

Two New Components from an Association of Marine Sponges Poecillastra sp. and Jaspis sp. and Their Inhibitory Effects on Biomarkers for Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH), characterized by the enlargement of the prostate gland and subsequent lower urinary tract symptoms, poses a significant health concern for aging men with increasing prevalence. Extensive efforts encompassing in vitro and in vivo models are underway to identify novel and effective agents for the management and treatment of BPH. Research endeavors are primarily channeled toward assessing the potential of compounds to inhibit cell proliferation, curb inflammation, and display anti-androgenic activity. Notably, through screening aimed at inhibiting 5-alpha reductase type 2 (5αR2) in human prostatic cells, two acyl compounds (1 and 2) were isolated from a bioactive fraction sourced from an association of marine sponges Poecillastra sp. and Jaspis sp. The complete structure of 1 was determined as (Z)-dec-3-enony (2S, 3S)-capreomycidine, ascertained by JBCA and ECD comparison. While the absolute configurations of 2 remained unassigned, it was identified as a linkage of a 2, 7S*-dihydoxy-9R*-methyloctadecanoyl group with the 2-amino position of a tramiprosate moiety referred to as homotaurine. Evaluation of both compounds encompassed the assessment of their inhibitory effects on key biomarkers (5αR2, AR, PSA, and PCNA) associated with BPH in testosterone propionate (TP)-activated LNCap and RWPE-1 cells.

Zonal Growth Pattern of the Prostate Is Affected by Age and Body Mass Index.

PURPOSE: As men age, the prostate continues to grow on average 2.5% per year. While the variable growth rate of the total prostate gland is recognized, the growth rate of different prostate zones remains largely unclear. We evaluated the growth patterns of the prostate zones and identified clinical parameters contributing to the zonal growth rates. MATERIALS AND METHODS: Prostate magnetic resonance imaging (MRI) data and clinical information were obtained retrospectively on 156 patients who had at least 3 prostate MRIs between 2003 and 2018. Different prostate zonal volumes were measured and analyzed. The outcome was analyzed using linear regression. RESULTS: We observed that prostate growth rates vary depending on body mass index (BMI), transition zone index (TZI), the prostate zone and 5-alpha reductase inhibitor (5ARI) use. The peripheral zone volume growth rates increased with age and peaked at 60-70 years of age (p=0.047), while the transition zone volume demonstrates continuous growth without a peak through all ages. BMI and TZI are associated with the growth rate of the peripheral zone (p=0.026, p <0.001, respectively) but not the transition zone growth rate. 5ARI use is significantly associated with the reduction in the transition zone growth rate (p=0.033), not the peripheral zone. In addition, patients with TZI greater than 60% had the most significant reduction in the transition zone growth rate while taking 5ARI (p <0.001). CONCLUSIONS: Transition and peripheral zones of the prostate grow at variable rates. BMI and TZI affect peripheral zone growth rate, while 5ARI use reduces the transition zone growth rate.

5α-Reductase Inhibitors Are Associated with Reduced Risk of SARS-CoV-2 Infection: A Matched-Pair, Registry-Based Analysis.

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a disproportionately severe effect on men, suggesting that the androgen pathway plays a role in the disease. Studies on the effect of castration and androgen receptor blockade have been mixed, while 5α-reductase inhibitor (5ARI) use in men with COVID-19 (2019 novel coronavirus) have shown potential benefits. We assessed the association of 5ARI use on risk of community acquired SARS-CoV-2 infection. MATERIALS AND METHODS: A total of 60,474 males in a prospective registry of people tested for SARS-CoV-2 between March 8, 2020 and February 15, 2021 were included. Using a matched cohort design, men using 5ARIs were matched 1:1 to non5ARI users. Independent analysis using unconditional multivariable logistic regression on the entire unmatched data set was completed for validation. Primary outcome measures were the association of 5ARI use on rates of SARS-Cov-2 positivity and disease severity. RESULTS: Of the men 1,079 (1.8%) reported 5ARI use and 55,100 were available for matching. The final matched cohorts included 944 men each. Mean duration of use was 60.4 months (IQR 17-84 months). Absolute risk for infection was significantly lower in 5ARI users compared to nonusers, 42.3% (399/944) vs 47.2% (446/944), respectively (absolute risk reduction [ARR] 4.9%, OR 0.81, 95% CI 0.67-0.97, p=0.026). Unconditional multivariable logistic regression analysis of the entire study cohort of 55,100 men confirmed the protective association of 5ARI use (ARR 5.3%, OR=0.877, 95% CI 0.774-0.995, p=0.042). Use of 5ARIs was not associated with disease severity. CONCLUSIONS: Use of 5ARIs in men without prostate cancer was associated with a reduction in community acquired SARS-CoV-2 infection.