Use Of 5-alpha Reductase Inhibitors Research Articles

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.

The effect of tranexamic acid on perioperative blood loss in transurethral resection of the prostate: A double-blind, randomized controlled trial.

Bleeding and bleeding-related complications remain common after bipolar transurethral resection of the prostate (TURP) for benign prostatic hyperplasia. This may possibly lead to prolonged postoperative irrigation, catheterization, and hospital stay. The objective of this trial was to evaluate the effect of high-dose tranexamic acid (TXA) on perioperative blood loss in patients treated with bipolar TURP for prostate sizes between 30 and 80 g. We conducted a single-center, prospective, double-blind, randomized controlled trial. Eighty patients were screened for inclusion between March 2020 and January 2023. After exclusion, 65 patients were randomized in two comparable groups. The TXA group (31 patients) received a TXA intravenous loading dose of 10 mg/kg over 30 min before induction, followed by a maintenance dose of 5 mg/kg/h over 12 h. The placebo group (34 patients) received an equal dose of saline infusion. We measured age, weight, preoperative prostate size, anticoagulant use, 5-alpha reductase inhibitor use, preoperative urinary tract infection, American Society of Anesthesiologists score, difference in pre- and 24 h postoperative hemoglobin and hematocrit levels, operative time, resected adenoma weight, duration of postoperative irrigation, total amount of postoperative irrigation fluid, indwelling catheter time, duration of hospital stay, blood transfusion rate, and 4-week complication rate. Baseline characteristics in both groups were comparable. Postoperative hemoglobin decrease in TXA versus placebo group was 1 versus 1.6 mg/dL, respectively (p = 0.04). In addition, the amount of postoperative irrigation fluid (10.7 vs. 18.5 L), irrigation time (24.3 vs. 37.9 h), catheterization time (40.8 vs. 53.7 h), and hospital stay (46.9 vs. 59.2 h) were statistically significant in favor of TXA use. No blood transfusions were carried out. Four-week complication rate was comparable between the two groups. Perioperative high-dose TXA seems beneficial in reducing hemoglobin loss, postoperative irrigation, catheterization time, and hospital stay in bipolar TURP for prostate sizes between 30 and 80 g, without increased risk of TXA-related thromboembolic events.

Use of 5-Alpha Reductase Inhibitors in Dermatology: A Narrative Review.

Finasteride and dutasteride are 5-alpha reductase selective inhibitors (5ARIs). They were introduced as therapeutic agents for the treatment of benign prostatic hyperplasia in 1992 and 2002, respectively; finasteride has also been approved for the treatment of androgenetic alopecia since early 2000. These agents inhibit the conversion of testosterone (T) to 5α-dihydrotestosterone (5α-DHT), limiting steroidogenesis and playing a crucial role in the physiological function of the neuroendocrine system. Therefore, it has been proposed that blocking androgen synthesis with the use of 5ARIs would be beneficial in the treatment of various diseases related to states of hyperandrogenism. This review describes the dermatological pathologies in which 5ARIs have been used as part of the treatment, evaluation of the efficacy, and knowledge of the safety profile. Specifically, we discuss the application of 5ARIs in androgenetic alopecia, acne, frontal fibrosing alopecia, hirsutism, and the implications of adverse events associated with its use to inform about the applications of 5ARIs in general dermatology practice.

The Use of 5-Alpha Reductase Inhibitors Improves the Detection of Prostate Cancer by Increasing Opportunities for Repeated Prostate-Specific Antigen Testing: A Decade-Long (2007–2016) Nationwide Observational Study in Korea

Purpose: The aim of this study was to investigate the influence of taking 5-alpha reductase inhibitors (5ARIs) on the detection of prostate cancer (PCa), considering the reported low uptake of prostate-specific antigen (PSA) testing among Korean men.Materials and Methods: From Korean National Health Insurance Sharing Service data, the number of men older than 40 years who were prescribed 5ARIs from 2007 through 2016 was identified. The association of 5ARI prescriptions with newly registered PCa was analyzed.Results: In total, 1,528,128 men who took 5ARIs for a mean of 1.523±2.221 years were identified. Among 138,614 patients with PCa, 68,529 (49.4%) took 5ARIs and 70,085 did not. The incidence of PCa was significantly higher in the 5ARI group than in the non-5ARI group during all study years (p<0.001) except for 2007. Adjusted for age, the non-5ARI group had a significantly lower likelihood of PCa detection (hazard ratio [HR], 0.854; p<0.001) and radical prostatectomy, including robot-assisted procedures (HR, 0.834, p<0.001). The mean number of PSA tests was about 2 times higher in the 5ARI group than in the non-5ARI group (3.98 vs. 2.18, p<0.001). Among the subjects who took 5ARIs, the incidence of PCa increased up to 3 years of administration, followed by a decreasing trend thereafter (p<0.001).Conclusions: From this observational study in a country with limited PSA testing uptake, the prescription of 5ARIs, for which repeated PSA testing is encouraged to select suitable patients, enhances the detection of PCa, but does not prevent its development.

Effects of 5-alpha reductase inhibitors prior to Holmium Laser Enucleation of the prostate: Does increased adenoma density result in prolonged morcellation times?

IntroductionThe use of 5-alpha reductase inhibitors (5-ARIs) has been shown to improve lower urinary tract symptoms (LUTS) and decrease prostate size in men with benign prostate hyperplasia (BPH). 5-ARI therapy could increase prostate tissue density through increased collagen deposition and contraction of stromal/epithelial components. Increased tissue density could prolong morcellation times, but the effects of preoperative 5-ARI exposure on morcellation efficiency during Holmium Laser Enucleation of the Prostate (HoLEP) are not well described. Herein, we examine outcomes after HoLEP of patients on pre-operative 5-ARIs.MethodsA retrospective review of patients undergoing HoLEP by an expert surgeon from Jan – Oct 2021 was performed. Student t-tests and chi-square tests were performed for continuous and categorical variables, respectively. Matched-pair analysis was performed using SPSS v28 (IBM, 2022). A p-value <0.05 was determined statistically significant. All other statistical analyses were performed using SAS v9.4 (SAS, 2019).ResultsA total of 322 patients underwent HoLEP during the study period and 84 patients had pre-operative 5-ARI exposure. Patients in the 5-ARI group had larger preoperative prostate size (p = 0.016). Morcellation time was longer (p=0.01), specimen weight was higher (p=0.02), and morcellation efficiency (p=0.02) was lower in the 5-ARI group. After matching, there were 67 patients in each chort (total 134) and these associations for size, morcellation time, specimen weight, and morcellation efficiency were no longer seen (p=0.8, 0.6, 0.5, and 0.7, respectively). Furthermore, no associations between 5-ARI and post-operative admissions or ED visits were noted.ConclusionIn this retrospective study, preoperative use of 5-ARIs did not affect enucleation or morcellation efficiency. Thus, preoperative 5-ARI therapy does not appear to alter outcomes after HoLEP.

MP28-16 THE ASSOCIATION OF NEW ONSET DIABETES AND MEDICAL THERAPY FOR BENIGN PROSTATIC HYPERPLASIA

INTRODUCTION AND OBJECTIVE:Long-term medical management of benign prostatic hyperplasia (BPH) includes use of 5-alpha reductase inhibitors (5ARI) and alpha-blockers (AB). Studies have demonstrated ...

Identifying Risk Factors for MRI-Invisible Prostate Cancer in Patients Undergoing Transperineal Saturation Biopsy

PurposeProstatic multi-parametric magnetic resonance imaging (mpMRI) has markedly improved the assessment of men with suspected prostate cancer (PCa). Nevertheless, as mpMRI exhibits a high negative predictive value, a negative MRI may represent a diagnostic dilemma. The aim of this study was to evaluate the incidence of positive transperineal saturation biopsy in men who have negative mpMRI and to analyse the factors associated with positive biopsy in this scenario.Patients and MethodsA retrospective study of men with normal mpMRI and suspicion of PCa who underwent saturation biopsy (≥20 cores) was carried out. A total of 580 patients underwent transperineal MRI/transrectal ultrasound fusion targeted biopsies or saturation prostate biopsies from January 2017 to September 2020. Of them, 73 had a pre-biopsy negative mpMRI (with Prostate Imaging – Reporting and Data System, PI-RADS, ≤2) and were included in this study. Demographics, clinical characteristics, data regarding biopsy results and potential predictive factors of positive saturation biopsy were collected. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for MRI-invisible PCa.ResultsThe detection rate of PCa with saturation biopsy in patients with negative MRI was 34/73 (46.58%). Out of 34 MRI-invisible prostate cancers detected, 12 (35.29%) were clinically significant PCa (csPCa) forms. Regarding factors of positive biopsy, in univariate analysis, the use of 5-alpha reductase inhibitors and free:total prostate-specific antigen (PSA) ratio were associated with the result of the saturation biopsy. In multivariate analysis, only an unfavourable free:total PSA ratio remained a risk factor (OR 11.03, CI95% 1.93–63.15, p=0.01). Furthermore, multivariate logistic analysis demonstrated that prostate volume >50mL significantly predicts the absence of csPCa on saturation biopsy (OR 0.11, 95% CI 0.01–0.94, p=0.04).ConclusionA free:total PSA ratio <20% is a risk factor for MRI-invisible PCa. Saturation biopsy could be considered in patients with suspected PCa, despite having a negative MRI.

Association of 5-Alpha Reductase Inhibitor Use with Prostate Specific Antigen Level at the Time of Urology Referral in a Retrospective Cohort at a Large, Integrated Health Care System.

5-Alpha reductase inhibitor (5-ARI) use leads to a 50% decline in serum prostate specific antigen (PSA) without a concomitant decrease in prostate cancer (PCa) risk. We hypothesize that failure to account for the effect of 5-ARI use on serum PSA leads to increased PCa risk at urology referral among 5-ARI users. This is a retrospective cohort study for the years 2018-2019. Atrium Health is a large, vertically integrated health system with over 900 care locations in North Carolina and South Carolina. Men ≥40 years old during 2018-2019 who had a PSA test performed were included. We determined differences in corrected serum PSA level at the time of referral to urology. 5-ARI users and nonusers were compared using the chi-square test, Student's t-test and gamma regression. From 2018-2019, there were 91,368 men who underwent PSA testing, including 2,939 5-ARI users. At referral, 5-ARI users had similar uncorrected median PSA (5.8 vs 5.6 ng/ml, p=0.05). After correcting for the effect of 5-ARIs on PSA, 5-ARI users had a median PSA of 11.6 ng/ml at urology referral, compared to 5.6 ng/ml in nonusers. Men taking 5-ARIs have higher corrected serum PSA at time of referral to urology. As the unadjusted PSA at referral to urology for PCa risk was similar between 5-ARI users and nonusers, this indicates that the effect of 5-ARI use on serum PSA levels is not routinely accounted for when assessing PCa risk.

Clinical characteristics and oncological outcomes in negative multiparametric MRI patients undergoing robot-assisted radical prostatectomy.

Efforts are ongoing to try and find ways to reduce the number of unnecessary prostate biopsies without missing clinically significant prostate cancers (csPCa). The utility of multiparametric magnetic resonance imaging (mpMRI) in detecting prostate cancer (PCa) shows promise to be used as triage test for systematic prostate biopsy. Our aim is to Study clinical parameters and oncological outcomes in men with negative mpMRI (nMRI; PI-RADS v2 scores of ≤ 2) who underwent robot-assisted radical prostatectomy (RARP) to evaluate nMRI's practicality as a biopsy triage test. Retrospective analysis of 331 men with nMRI who underwent RARP between 2014 and 2020 compared with men with positive mpMRI (pMRI; PI-RADS v2 scores ≥ 3, N = 1770). csPCa was defined as Gleason score ≥ 3 + 4 and biochemical recurrence (BCR) was defined as PSA > 0.2 ng/ml on two occasions. Biopsies were graded with the International Society of Urologic Pathology [ISUP] grade. Descriptive statistics for nMRI and pMRI were performed. Mann-Whitney U test was used for continuous variables and χ 2 for categorical variables. Univariable and multivariable regression analyses were performed. Univariable analysis shows statistically significant difference (p < .05) between median age (nMRI-61 years vs. pMRI 63 years), race (higher incidence of nMRI in African American men), use of 5-alpha reductase inhibitors (higher rate in nMRI). While incidence rates of family history of PCa, suspicious digital rectal examination (DRE) findings, median PSA levels and 4Kscore, were lower in nMRI versus pMRI. Rates of positive surgical margins and BCR were comparable in nMRI versus pMRI. Biopsy ISUP Grades I and II upgraded by 51% and 12%, respectively in final pathology. African American race and no history of the prior negative biopsy were significant predictors for upgrading. Men with nMRI pose diagnostic challenges as they tend to be younger patients with lower rates of suspicious DRE findings and lower 4K scores, yet comparable oncological outcomes in csPCa rates, positive surgical margins, and BCR rates.

Impact of 5-ALPHA reductase inhibitor use on prostate cancer risk at the time of urology referral.

226 Background: 5-alpha reductase inhibitors (5-ARIs) are commonly used medications for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. One of the consequences of 5-ARI use is a 50% drop in serum PSA without a concomitant reduction in prostate cancer (PCa) risk. Previous work has suggested that 5-ARI use is associated with worse PCa-specific outcomes. The objective of this study was to evaluate the impact of 5-ARI use on patients’ PCa risk at the time of referral from primary care to urology. Methods: This retrospective cohort study included all men ≥ 40 years who had a PSA resulted between 2018-2019 and were seen in an ambulatory setting. PSA testing was determined through laboratory data in the electronic health record (EHR). Clinical and demographic data were collected for all men. 5-ARI use was determined through orders in the EHR. Men were assigned PCa risk according to both the Prostate Biopsy Collaborative Group (PBCG) and Prostate Cancer Prevention Trial (PCPT) risk calculators. PSA values were doubled for 5-ARI users prior to calculating risk. Referral to urology for PCa risk was determined using the narrative reason for referral associated with the referral order. Results: Between 2018-2019, 91,368 men had a PSA test, including 2,939 5-ARI users, and 88,429 non-users. Uncorrected median PSA and the proportion of men referred to urology for PCa risk were similar between the two groups (p = 0.60 and p = 0.17, respectively). Of men referred to urology for PCa risk, 5-ARI users had similar uncorrected PSA to non-users (p=0.86) but higher risk for high grade PCa once PSA correction was performed, median (IQR) 48% (24%) vs 28% (18%) using the PBCG and 21% (17%) vs 10% (10%) using the PCPT (p &lt; 0.01 for both) (Table). Conclusions: Men taking 5-ARIs have significantly higher risk for high-grade PCa at time of referral to urology than non-users in this cohort. As the unadjusted PSA at referral to urology for PCa risk was the same between 5-ARI users and non-users, this indicates that the effect of 5-ARI use on serum PSA levels is not routinely accounted for when assessing PCa risk. Further study on interventions to account for 5-ARI use when screening for PCa are warranted. [Table: see text]

The Use of 5-Alpha Reductase Inhibitors and Alpha-1 Blockers Does Not Improve Clinical Outcome in Male Patients Undergoing Radical Cystectomy for Bladder Cancer in Quebec, Canada.

Existing literature suggests that bladder cancer (BC) outcome may be improved when patients use 5α-reductase inhibitors and/or α1-blockers, but such a conclusion may be subject to publication bias. We evaluated whether preoperative use of 5α-reductase inhibitors or α1-blockers was associated with improved clinical outcomes in a cohort of patients with BC undergoing radical cystectomy (RC). Using provincial health administrative databases, we retrospectively identified male BC patients undergoing RC in Quebec province between 2000 and 2015, and we collected data from 2 years before RC until December 2016 or death. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, propensity score matching, and uni- and multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, annual RC volume of each hospital and surgeon, neoadjuvant chemotherapy use, and type of bladder diversion. Of the 2822 patients included, 284 patients used 5α-reductase inhibitors and 1001 patients used α1-blockers prior to surgery. Median follow-up time was 7.7 years. Patients who used 5α-reductase inhibitors or α1-blockers were generally older, had more comorbidities, and were treated more recently in academic centers. Overall, bladder cancer-specific and recurrence-free survival did not differ significantly between those using 5α-reductase inhibitors prior to surgery and controls who never used 5α-reductase inhibitors. Adjusted hazard ratios were 1.03 (95% confidence interval [CI], 0.88-1.21) for overall survival, 1.12 (95% CI, 0.92-1.36) for bladder cancer-specific survival, and 1.19 (95% CI, 0.99-1.42) for recurrence-free survival. The aforementioned outcomes were significantly worse in patients who used α1-blockers prior to surgery compared to controls, with respective adjusted hazard ratios of 1.15 (95% CI, 1.04-1.27), 1.19 (95% CI, 1.05-1.35), and 1.18 (95% CI, 1.05-1.33). Preoperative use of 5α-reductase inhibitors and α1-blockers did not improve clinical outcome in our cohort of male patients undergoing radical cystectomy for bladder cancer.

Ethnic variation in prostate cancer detection: a feasibility study for use of the Stockholm3 test in a multiethnic U.S. cohort.

The Stockholm3 test improves Gleason Grade Group ≥2 (GG ≥ 2) prostate cancer (PC) detection, however it has not been evaluated in an American cohort where clinical practice patterns and ethnicity differ. We aimed to identify subgroups within a Stockholm population with PC risk profiles matching American ethnicity-specific subgroups and compare the detection of PC and describe Stockholm3 performance within these subgroups. All men age 49-70 years presenting for prostate biopsies were evaluated at UIC from 2016 to 2019, as well as men in Stockholm from 2012 to 2014 in the STHLM3 study. Propensity scores (PS) were estimated for each person using logistic regression for age, PSA, prostate volume, family history of PC, 5-alpha reductase inhibitor use, and prior biopsy. 3:1 PS matching was performed for Stockholm to Chicago ethnicity-specific cohorts and odds ratios (OR) were computed to compare detection of GG ≥ 2 PC between groups. 504 Chicago men and 6980 Stockholm men were included. In African American (AA) men, 51% had GG ≥ 2 PC detected, while in risk-matched Stockholm men, 34% had GG ≥ 2 PC detected (OR: 2.1, p < 0.001). There was no statistical difference in GG ≥ 2 PC detected when matching Stockholm men to non-Hispanic Caucasian men (31% vs. 24%, OR: 0.7, p = 0.30) or Hispanic Caucasian men (31% vs. 27%, OR: 1.2, p = 0.42). The AUC for the Stockholm3 test of the matched Stockholm cohorts for AA, non-Hispanic Caucasian, and Hispanic Caucasian men was 0.85, 0.89, and 0.90, respectively. Using statistical techniques to simulate a multi-ethnic Chicago cohort within the STHLM3 population, we found an excess risk of GG ≥ 2 PC among AA men. Our hypothesis that the Stockholm3 may have good predictive value in a multiethnic cohort is strengthened, and that recalibration to at least AA men seems likely to be needed to obtain well-calibrated predictions.

PD52-08 CHANGES IN BLOOD LEVELS OF PROSTATE KALLIKREIN-RELATED AND MICROSEMINOPROTEIN-BETA MARKER LEVELS FOLLOWING 5ARI THERAPY: DATA FROM 500 PCPT-PARTICIPANTS

INTRODUCTION AND OBJECTIVE:The use of 5-alphareductase inhibitors (5ARIs) to treat men with benign prostate hyperplasia reduces PSA levels by approximately half, and limited data suggest that free ...

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

BACKGROUND: Prior research implicates the androgen receptor pathway as important in bladder cancer progression and recurrence. In particular, use of 5-alpha reductase inhibitors (5-ARIs) appears to improve bladder cancer outcomes. This study aims to determine if concomitant use of 5-ARIs with intravesical Bacille Calmette-Guérin (BCG) decreases recurrences in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS &amp; METHODS: This retrospective analysis included male patients diagnosed with NMIBC who were treated with induction intravesical BCG at our institution from 2013 to 2018. Patients were excluded who received prior induction BCG. Recurrence and progression-free survival were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards and Poisson events models. RESULTS: We identified 206 male patients, of whom 39 received 5-ARIs and 167 did not. Most patients (72.8%) received &gt;6 instillations of BCG, with 20.4% completing all induction and maintenance treatments during a median follow up of 3.31 years. There were no significant differences in recurrence or progression-free survival between 5-ARI users or non-users (59% vs 55.7%; p = 0.72 and 97.4% vs 98.2%; p = 1.00, respectively). Similarly, no differences in the number of recurrences between groups was observed (p = 0.78). However, the proportion of patients who completed all prescribed BCG installations was higher among 5-ARI users (39.7% vs 17.9 %, p = 0.07). CONCLUSIONS: In contrast to prior reports, our study does not suggest that 5-ARI use decreases the recurrence rate in men receiving induction BCG for NMIBC. However, our results suggest 5-ARI use may improve patient tolerance to BCG.

Demographic and Pharmaceutical Predictors of Unfavorable Prostate Cancer

Both prospective and retrospective series have explored risk factors for developing aggressive prostate cancer. Predictors of higher grade disease include 5-alpha reductase inhibitor use, older age, and African American background. There is a paucity of literature that has applied similar risk factors to the current model of unfavorable intermediate and high risk disease. This study reports demographic and pharmacologic predictors of being treated for unfavorable intermediate and high risk prostate cancer at a busy academic center. A total of 3445 patients were treated for prostate cancer where baseline demographics, pharmacologic history, and clinicopathologic features were available. The mean age was 67.8 years (41, 93) with a mean PSA of 9.23ng/ml (0.3, 205). 34.2%, 31.7%, 19.1%, and 15.0% of patients were diagnosed with Gleason 6 (3+3), Gleason 7 (3+4), Gleason 7 (4+3), and Gleason 8-10 prostate cancer. The Zumsteg Classification System was applied to categorize patients into low (28.6%), favorable intermediate (22.6%), unfavorable intermediate (30.8%), and high risk (18.0%) disease groups. Unfavorable Prostate Cancer (UPC) was defined as being diagnosed with unfavorable intermediate or high risk disease (48.8%). Univariate and multivariate logistic regression was used to determine those factors that portended for UPC. 64.5% of patients taking 5-alpha reductase medication were diagnosed with UPC, compared to 53.6% of those who did not take this class of medication (p<.0001). This finding was also seen in men who took metformin compared to those who did not (62.4% vs. 53.4%, p<.0001). Men older than age 65 had a higher risk of presenting with UPC compared to younger men (47.8% vs. 34.6%, p<.0001), as did those with a first degree relative who had been diagnosed with prostate cancer (52% vs. 48.1%, p<.0001). Asian men had a higher risk of aggressive disease than men who self-identified as white or African American (72.4% vs. 51.2% and 52.3%, respectively, p<.0001). Men with a comorbidity of HIV were also more likely to exhibit UPC (68.8% vs. 54.4%, p<.0001). On multivariate analysis, older age (OR 2.021, CI 1.735-2.354, p<.0001), the use of 5-alpha reductase inhibitors (OR 2.508, CI 1.228-5.122, p=.012) or metformin (OR 1.334, CI 1.033-1.722, p=.037), and Asian American background (OR 2.481, CI 1.001-6.146, p=.05) predicted for being treated for UPC. In a large hospital series, nearly half of those treated for prostate cancer were diagnosed with UPC. Consistent with previous phase 3 data correlated with higher grade disease, 5-alpha reductase inhibitor use was associated with UPC in this cohort. In keeping with retrospective published series, older men had a higher risk of being treated with more aggressive disease. While prostate cancer is less common in Asian Americans and metformin’s role in prostate cancer therapeutics remains investigational, diagnosis with either classification was associated with UPC in this series.

Clinical Course of the Benign Prostate Hyplasia Patients during the Intermittent Use of 5-Alpha Reductase Inhibitors

Clinical Course of the Benign Prostate Hyplasia Patients during the Intermittent Use of 5-Alpha Reductase Inhibitors

A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Postfinasteride Syndrome

ObjectiveTo quantify reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS), create a demographic of patient reports, and examine the cluster of symptoms to correlate consistency of postfinasteride syndrome (PFS) complaints. PFS is a provisional diagnosis encompassing a cluster of sexual, physical, and psychological and/or neurologic symptoms associated with 5-alpha reductase inhibitor use that emerge or continue after discontinuation of medication. Materials and MethodsFAERS dataset of 5-alpha reductase inhibitors from April 2011 to October 2014 was obtained. Each FAERS report had 16 categories for completion, but not every report was fully completed. Statistical analysis compared variables of interest between the 2 doses of finasteride (1 mg vs 5 mg). ResultsFrom FAERS, 2048 monotherapy cases were identified: 1581 of finasteride 1 mg, 240 of finasteride 5 mg, and 226 of unreported doses. Possibly related to labeling changes, from 2011 to 2014, there was a significant increase in adverse events (AEs) reported involving 1 mg dosing. Finasteride use was reported with many sexual AEs including diminished libido, erectile dysfunction, and ejaculatory complaints. Other common AEs included dermatologic, metabolic, and psychological and/or neurologic complaints. There were more AE reports with the 1 mg dose than the 5 mg dose. One case of dutasteride reported back pain, not generally attributed to PFS. ConclusionFAERS data suggests that finasteride exposure is reported with a diverse collection of symptoms, particularly in younger men on 1 mg dosage compared to older men on 5 mg. Many of these complaints fall well out of the realm of previously established AEs from long-term controlled studies.

The Use of 5-Alpha Reductase Inhibitors to Manage Benign Prostatic Hyperplasia and the Risk of All-cause Mortality

ObjectiveTo compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. MethodsWe employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. ResultsIn this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). ConclusionAmong men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.

Effects of 5-alpha reductase inhibitors: new insights on benefits and harms.

The use of 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) and other diseases has been proposed and studied. However, the controversy about its benefits and harms for other diseases has persisted. In this review, we will discuss the newly identified effects of 5ARIs based on recently published studies. These drugs are currently recommended in clinical guidelines for BPH. However, the reporting of adverse effects, including sexual dysfunction as well as neurologic, endocrine, and cardiovascular effects, have been controversial. There are reports of additional effects of 5ARI in prostate cancer and bladder cancer. Although 5ARIs have been prescribed for the treatment of androgenic alopecia (AGA), postfinasteride syndrome can result, with symptoms that range from sexual dysfunction to muscle atrophy. Clinical applications of 5ARIs have been established for the treatment of BPH and AGA from a series of randomized controlled trials. The adverse effects of 5ARIs affect only a small proportion of treated patients and can be resolved with discontinued treatment. It will be necessary to establish the mechanism by which 5ARIs elicit these effects through better designed studies.

Clinical changes of withdrawal finasteride in patients with benign prostatic hyperplasia

Objective To study changes in lower urinary tract symptoms, serum prostate-specific antigen, and prostate volume after discontinuation of finasteride combination therapy in patients with benign prostatic hyperplasia. Methods From December 2011 to June 2016, clinical data were collected retrospectively from 83 men more than 55 years of age with moderate to severe BPH symptoms (IPSS≥8). The men were classified into group A (n=43) and group B (n=40) according to the use of finasteride therapy. A combination of finasteride 5 mg with tamsulosin 0.2 mg was given daily to all patients for one year. For the next one year, group 1 received the combination therapy and group 2 received tamsulosin 0.2 mg monotherapy only. The IPSS, PSA level, and prostate volume were measured at baseline and at 12 and 24 months according to the use of dutasteride. Results Withdrawal of finasteride led to significant deterioration of LUTS, increased PSA level, and increased prostate volume. The repeated-measures analysis of variance showed that the changes in IPSS, PSA level, and prostate volume over time also differed significantly between groups A and B (P<0.001). Conclusions Discontinuation of finasteride during combination therapy results in prostate regrowth and deterioration of LUTS. The PSA level is also affected by the use of 5-alpha reductase inhibitors(5ARI). Therefore, regular check-up of the IPSS and PSA level may be helpful for all patients who either continue or discontinue the use of 5ARI. Key words: Prostatic Hyperplasia; Prostate-Specific Antigen