5-ARI Use Research Articles

Testosterone and 5 Alpha Reductase Inhibitor (5ARI) in Benign Prostatic Hyperplasia (BPH): A historical perspective

This paper provides a review of the historical and scientific evolution of testosterone and 5ARI research. It chronicles the evolution from early empirical practices like castration, through the formal discovery of testosterone in the 20th century, to the eventual synthesis of testosterone and identification of Leydig cells. Testosterone’s crucial role in male development and its influence on the development and maturation process of the prostate gland are also presented. The introduction of 5ARIs in the 1990s, such as finasteride, marked a significant advancement in managing BPH by reducing dihydrotestosterone (DHT) levels. The controversy regarding the therapeutic use of 5ARIs is discussed, given concerns about their association with high-grade prostate cancer and other systemic risks. Likewise, emerging evidence challenges the traditional view that testosterone exacerbates prostate conditions, suggesting that testosterone replacement therapy (TRT) may improve symptoms of low testosterone without increasing BPH symptoms, prostate cancer (PCa), or cardiovascular risk. Several new studies are discussed suggesting that low or declining testosterone level could be a risk factor for prostate tumorigenesis. This review emphasizes the need for continued research on Testosterone and 5ARI to further define their role in men’s health.

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data

BackgroundIncreasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. MethodsThe MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. ResultsOverall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58–1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87–1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. ConclusionsThe use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

The association of 5-alpha reductase inhibitors treatment with prostate cancer in benign prostate hyperplasia patients: A population-based case-control study

Purpose: Benign prostatic hyperplasia (BPH) is the most common cause of difficult voiding in elderly men. Alpha-blockers and 5-alpha reductase inhibitors (5ARIs) are evidence-based standards of care in treating BPH according to current guidelines. We have conducted a nationwide population-based study to evaluate the association of 5ARIs treatment with prostate cancer in patients with benign prostate hyperplasia. Materials and methods: Between 2005 and 2010, patient data from the National Health Insurance Research Database were obtained. Newly diagnosed patients with BPH were divided into 2 groups: prostate cancer group and BPH group. We conducted a retrospective study on their history of medication usage with 5ARIs. Results were compared with a matched noncancerous control group. The outcome measurements were the incidence and the prostate cancer diagnosis-free survival rate after the BPH index date. Statistical analyses included t test, chi-square test, multivariable logistic regression analysis, and Kaplan-Meier curves with log-rank tests. Results: A total of 18,620 newly diagnosed patients with BPH were selected. After eliminating patients according to the exclusion criteria, a total of 17,716 patients were enrolled as the study subjects. Among them, 530 patients (2.99%) developed prostate cancer and 17,186 (97.01%) did not. The mean age of the total case-control study was 69.1 years. The odds ratio of prostate cancer in patients with BPH with 5ARIs usage was 1.14 with a P value of 0.539, indicating that the use of 5ARIs was not associated with a higher risk of developing prostate cancer. Multivariate analysis showed no significant intergroup difference in the risk of developing prostate cancer (odds ratio = 1.14, 95% CI: 0.75–1.74, P = 0.539). A subgroup survival analysis, observing the time interval from BPH diagnosis to the development of prostate cancer based on 5ARIs usage, revealed a nonsignificant difference in the prostate cancer diagnosis-free survival rate, with a P value of 0.3592. Conclusion: The 5ARI usage in patients with BPH was not associated with increased risk of developing prostate cancer. Furthermore, the prostate cancer diagnosis-free survival rate, when stratified based on 5ARIs usage, showed no statistically significant difference. Under our health insurance regulation and clinical practice, 5ARIs are consider safe in treating BPH.

5-α Reductase Inhibitors and Prostate Cancer Mortality

5-alpha-reductase-inhibitors (5-ARIs) are approved for treating benign prostatic hyperplasia (BPH) and have been found to reduce prostate cancer (PCa) risk by 25%. However, trials also have shown 5-ARIs to be associated with high-grade PCa. Whether 5-ARIs increase mortality among those with a diagnosis of PCa remains unclear. To determine long-term outcomes of clinically localized PCa arising in individuals taking 5-ARIs compared with nonusers. This population-based cohort study was conducted between January 2003 and October 2017. Eligible participants were men aged 65 years or older in Ontario, Canada, who developed clinically localized PCa with complete pathological abstraction from the Ontario Health Administrative Databases. Data analysis occurred from November 2017 to November 2022. 5-ARIs before PCa diagnosis. The primary outcomes were overall mortality and PCa-specific mortality. Cause-specific hazard models with inverse probability treatment weights (IPTW) were used to examine associations of 5-ARI use with mortality outcomes. Sensitivity analyses based on prediagnostic 5-ARI use, Gleason score, comorbidity, 5-ARI indication, prostate-specific antigen modeling, and statin use were also performed. The cohort included 19 938 patients with PCa. Of these, 2112 (10.6%; median [IQR] age, 74 [70-79] years) were 5-ARI users and 17 826 (89.4%; median [IQR] age, 71 [68-76] years) were nonusers. During a median (IQR) follow-up of 8.96 (6.28-12.17) years, 6053 (30.4%) died, including 1047 (5.3%) from PCa. 5-ARI use appeared to be associated with increased overall and PCa specific mortality in crude analyses; however, after IPTW, 5-ARI use was not associated with overall mortality (hazard ratio, 0.98; 95% CI, 0.90-1.07; P = .77) or PCa-specific mortality (hazard ratio, 1.02; 95% CI, 0.83-1.25; P = .84). In this population-based cohort study of 5-ARI use prior to PCa diagnosis including long-term follow-up and clinicopathologic details, prediagnostic 5-ARI use was not associated with PCa-specific or all-cause mortality. This study offers reassuring safety data for patients using 5-ARIs before PCa diagnosis for both BPH and chemopreventive reasons.

The impact of preoperative 5-alpha reductase inhibitors on functional outcomes and health-related quality of life following radical prostatectomy – A propensity score matched longitudinal study

ObjectivesWhile the impact of treatment with 5-alpha Reductase Inhibitors (5-ARI) on the risk of cancer-related mortality in men with prostate cancer (PC) has been extensively studied, little is known about the impact of preoperative 5-ARI use on patient-reported outcomes (PROs) following radical prostatectomy (RP).MethodsWithin our prospectively maintained institutional database of 5899 patients treated with RP for PC (2008– 2021), 99 patients with preoperative 5-ARI therapy were identified. A 1:4 propensity-score matched analysis of 442 men (n = 90 5-ARI, n = 352 no 5-ARI) was conducted. Primary endpoint was continence recovery using daily pad usage and ICIQ-SF. Health-related quality of life (HRQOL) was assessed using the validated EORTC QLQ-C30 and PR25 questionnaires. Multivariable Cox-regression-models tested the effect of preoperative 5-ARI treatment on continence-recovery (p < 0.05).ResultsPatients were followed up perioperatively, followed by annual assessments up to 60mo postoperatively. Preoperative mean ICIQ-SF score (2.2 vs. 0.9) was significantly higher in the 5-ARI cohort (p = 0.006). 24mo postoperatively, 68.6% (no 5-ARI) vs. 55.7% (5-ARI) had full continence recovery (p = 0.002). Multivariable Cox regression analysis, revealed preoperative 5-ARI treatment as an independent predictor for impaired continence recovery (HR 0.50, 95% CI 0.27–0.94, p = 0.03) In line, general HRQOL was significantly higher for patients without 5-ARI only up to 24mo postoperatively (70.6 vs. 61.2, p = 0.045). There was no significant impact of preoperative 5-ARI treatment on erectile function, biochemical recurrence-free survival and metastasis-free survival.ConclusionsPre-RP 5-ARI treatment was associated with impaired continence outcomes starting 24mo postoperatively, suggesting that preoperative 5-ARI treatment can impair the long-term urinary function recovery following RP.

Delayed hematuria after prostatic photovaporization: risk factors to know.

characterize delayed hematuria (DH) after photoselective vaporization of the prostate (PVP) and identify its associated risk factors. 1014 patients who underwent PVP at an expert center, from September 2005 through December 2021, were prospectively enrolled in a database registry. Risk factors of DH included age, prostate volume, ASA score, history of BPH surgery, history of prostate cancer, use of anticoagulation or 5ARIs, concomitant procedure, operative factors, and the duration of follow-up. The median operating time was 60 ± 11 min. The median specific applied energy was 318,500 Joules ± 101,347. After PVP, the mean catheterization duration was 1.6 days with a postoperative hospitalization time of 1.8 days. The median follow-up was 52 months (range 2-95months). Hematuria occurred in 206 patients (20.3%), with 10% requiring an ER visit and 8.3% requiring hospital admission, transfusion or endoscopic clot removal. Almost 80% of hematuria episodes occurred within the first 3months. The overall retreatment rate for clot retention was 3.7% after a mean time of 50months. Hematuria-free survival was 97.2% after 1year, and 89.3% after 4years. Delayed hematuria occurred in 32 patients (3.1%). In the multivariate analysis, age, preoperative prostate volume, anticoagulant use, total applied energy, lasing time and operative time were identified as risk factors for delayed hematuria after PVP. Larger prostate volume, longer operative time, longer lasing time, and use of oral anticoagulation increase the odds of delayed hematuria after PVP, while older age is protective.

Suicide and Intentional Self-harm Among Older Men Treated With 5-Alpha Reductase Inhibitor or Alpha-blockers for Benign Prostatic Hyperplasia

ObjectiveTo compare the risk of intentional self-harm (ISH) and suicide in older men using 5-α reductase inhibitors (5-ARIs) and alpha-blockers for benign prostatic hyperplasia (BPH). Observational research of older men with BPH suggested an increase in ISH with 5-ARI use compared with nonuse; we aimed to address potential confounding by indication with an active comparator reference group. MethodsUsing Medicare data linked to the National Death Index (NDI) from 2007-2016, we implemented a retrospective cohort design in males aged ≥65 years who initiated 5-ARI or alpha-blocker use for BPH. ISH was identified using ICD-9-CM and ICD-10-CM diagnosis codes. Suicides were identified through cause-of-death information from the NDI. We used inverse probability of treatment weighted Cox proportional hazards regression to compare time-to-event between treatment groups, with robust variance estimation. ResultsThe event rates for ISH and suicide, respectively, were 0.314 and 0.308 per 1000 person-years (PY) among 5-ARI users (n=181,675), and 0.364 and 0.382 per 1000PY among alpha-blocker users (n=850,476). For 5-ARI use relative to alpha-blocker use, hazard ratios (HRs) for ISH and suicide, respectively, were 0.88 (95% CI:0.62–1.25) and 0.82 (95% CI:0.54–1.24); for the composite outcome (non-fatal ISH or suicide), the HR was 0.88 (95% CI:0.66–1.16). Subgroup and sensitivity analyses supported these results. Conclusion5-ARI use was not associated with an increased risk for ISH or suicide compared to alpha-blocker use in older men with BPH. Study limitations included low event rates and potentially low sensitivity for ISH events.

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 Long-Term Impact of 5-alpha Reductase Inhibitors on the Development of Bladder Cancer and the Need for Radical Cystectomy: A Nationwide Observational Study.

To investigate the long-term effects of taking 5-alpha reductase inhibitors (5ARIs) on the development of bladder cancer (BC) and the implementation of radical cystectomy (RC), a standard procedure for advanced BC. From the National Health Insurance Sharing Service database, males aged over 40 years who underwent serum prostate-specific antigen testing from 2006 through 2017 were identified, which is required for the prescription of 5ARIs. The association between the administration duration of 5ARIs and the practice for BC was analyzed. Of the 3,843,968 subjects, 1,514,713 (39.4%) took 5ARIs for an average of 1.53 years, remaining 2,329,255 (60.6%) as non-5ARI counterparts. The incidence of BC was higher in the non-5ARI than in the 5ARI group (1.25% vs. 0.87%, p<0.001), as was the implementation rate of RC (11.1% vs. 10.4%, p=0.037). In a multivariate analysis, the non-5ARI group had a significant risk of BC (hazard ratio [HR]=2.289, 95% confidence interval [CI]=2.241-2.338) and RC (HR=2.199, 95% CI=2.061-2.348) than the 5ARI group. Among the 5ARIs group, though the incidence of BC was maintained (slope=-0.002 per year, p=0.79) after an initial increase for two years, the rate of RC decreased (slope=-1.1, p<0.001) consistently for ten years during the administration. Compared to the untreated group, 5ARIs use was associated with lower rates of BC and RC. In contrast to the increase in BC seen with short-term use of less than two years, long-term use of 5ARIs decreased the rate of RC in a duration-dependent manner for ten years, suggesting a strategy to prevent disease progression.

Incidental Prostate Cancer Diagnosis Is Common After Holmium Laser Enucleation of the Prostate

ObjectiveTo determine the incidence of incidental prostate cancer detection (iPCa) after holmium laser enucleation of the prostate (HoLEP). The published rate of iPCa after HoLEP is widely variable from 7-23% and we aim to define preoperative risk factors for iPCa to inform risk adjusted preoperative evaluation for prostate cancer. MethodsConsecutive patients undergoing HoLEP from 2018-2022 were included and comprehensive clinical data abstracted from a prospectively maintained database. iPCa was defined as a diagnosis of PCa on pathologic examination of the HoLEP specimen. Patients with and without iPCa were compared with respect to pre-operative clinical variables. ResultsOf 913 HoLEP patients, 183 (20%) were diagnosed with iPCa. Most patients (95%) had a pre-operative PSA, 9% had negative MRI, and 30% had negative prostate biopsy. On multivariable analysis, PSA density (OR 1.06; 95% CI 1.03, 1.10; p<0.001), preoperative biopsy status (OR 0.47, CI 0.30, 0.75; p=0.002), and current 5-alpha reductase inhibitor (5-ARI) use (OR 0.64, CI 0.43, 0.97; p=0.034), were associated with iPCa diagnosis. ConclusionsIn a significantly pre-screened population, we identified a 20% rate of iPCa after HoLEP. Preoperative characteristics associated with iPCa diagnosis included increasing age, increasing PSA density, and current 5-ARI use. However, these factors alone may be of limited clinical utility to prospectively identify patients at high risk of iPCa diagnosis. We suggest and advocate for development of a standardized, risk adapted evaluation focused on expanded use of imaging and selective biopsy to prioritize identification of clinically significant prostate cancers prior to non-oncologic surgery.

Finasteride and Dutasteride for the Treatment of Male Androgenetic Alopecia: A Review of Efficacy and Reproductive Adverse Effects

Finasteride and dutasteride are 5-α-reductase inhibitors (5-ARIs) used to treat androgenetic alopecia (AGA). This review evaluates the efficacy of 5-ARIs for treatment of men with AGA and the potential adverse effects on reproduction including sexual dysfunction, infertility, and teratogenicity. A broad literature review was conducted to search for publications on 5-ARI treatment in men with AGA. Hair counts, hair growth assessments, sexual adverse effects (erectile dysfunction, ejaculatory dysfunction, and decreased libido), change in sperm parameters (decreased sperm count, semen volume, sperm motility), and teratogenic drug concentration levels in semen were the measured outcomes of studies included in this literature review. Both finasteride and dutasteride are effective at treating hair loss in male AGA, with studies finding dutasteride was more efficacious than finasteride. Many studies reported sexual adverse effects of 5-ARIs that are uncommon and resolve spontaneously, although there remains no consensus with respect to the presence, severity, and duration of sexual adverse effects. 5-ARIs may have a negative impact on spermatogenesis although the clinical significance of this is unclear and discontinuation of these medications results in improved sperm parameters for most patients. Teratogenicity after paternal exposure is unlikely due to the low concentration of 5-ARIs absorbed in semen. Further research is needed to evaluate the effects of 5-ARI use on reproduction.

Evaluating the effects of preoperative treatment with 5-alpha reductase inhibitors in holmium laser enucleation of the prostate

Introduction and aimPatients treated with HoLEP are frequently treated with previous treatments, including 5-alpha-reductase inhibitors (5-ARIs). We investigated the impact of pretreatment with 5-ARIs on perioperative and immediate postoperative parameters in patients treated with HoLEP. Material and methodsA retrospective study was performed using a prospectively collected database including all patients treated with HoLEP at our center between January 2017 and January 2023. The resected tissue weight, enucleation and morcellation efficiency (enucleation weight/time and morcellation weight/ time), postoperative complications, hospital stay and hemoglobin drop have been analyzed. ResultsA total of 327 patients were included. Of these, 173 (52.9%) were treated with 5-ARIs. No differences were found among the perioperative parameters investigated to determine efficiency. No differences were observed in peri- or postoperative complications, hospital stay or hemoglobin drop. ConclusionsTherapy with 5-ARIs had no impact on the immediate postoperative outcomes of patients treated with HoLEP. In our cohort, we observed that the use of 5-ARIs did not affect surgical efficiency, enucleation or morcellation. Further multicenter studies will be necessary to validate these findings.

¿Tiene el tratamiento previo con inhibidores de la 5-alfa reductasa repercusión en la enucleación prostática con láser holmium? Resultados de un estudio prospectivo observacional y revisión de la literatura

Introduction and aimPatients treated with HoLEP are frequently treated with previous treatments, including 5-alpha-reductase inhibitors (5-ARIs). We investigated the impact of pretreatment with 5-ARIs on perioperative and immediate postoperative parameters in patients treated with HoLEP. Material and MethodsA retrospective study was performed using a prospectively collected database including all patients treated with HoLEP at our center between January 2017 and January 2023. The resected tissue weight, enucleation and morcellation efficiency (enucleation weight/time and morcellation weight/ time), postoperative complications, hospital stay and hemoglobin drop have been analyzed. ResultsA total of 327 patients were included. Of these, 173 (52.9%) were treated with 5-ARIs. No differences were found among the perioperative parameters investigated to determine efficiency. No differences were observed in peri- or postoperative complications, hospital stay or hemoglobin drop. ConclusionsTherapy with 5-ARIs had no impact on the immediate postoperative outcomes of patients treated with HoLEP. In our cohort, we observed that the use of 5-ARIs did not affect surgical efficiency, enucleation or morcellation. Further multicenter studies will be necessary to validate these findings.

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.

Five-alpha reductase inhibitors and risk of prostate cancer among men with benign prostatic hyperplasia: A historical cohort study using primary care data

Background: Five-alpha reductase inhibitors (5ARIs) are used in the management of benign prostatic hyperplasia (BPH). 5ARIs prevent the conversion of testosterone to dihydrotestosterone, which is important in prostate development. It has been suggested that 5ARIs can be used a chemopreventative agent for prostate cancer. The aim of this study was to assess the risk of prostate cancer associated with 5ARI use among men with BPH. Methods: Using Clinical Practice Research Datalink (CPRD) from 1992 to 2011 in UK, prostate cancer risk was retrospectively compared in men with a new diagnosis of BPH, with no history of prostate cancer who were treated with 5ARIs, to men treated with alpha blockers (ABs) and those given no pharmacological treatment. Incidence rate of prostate cancer was calculated by treatment group; the association between BPH treatment group and prostate cancer was estimated by a multivariate Cox model. Results: 77,494 men with newly diagnosed BPH were included. The crude incidence rate of prostate cancer was 892.4 cases per 100,000 person-years amongst those treated with 5ARIs, compared with 1209.0 and 1542.9 in those treated with ABs and untreated individuals, respectively. The HR adjusted for potential confounders was 0.79 (0.72-0.86) for 5ARI vs ABs and 0.72 (0.66-0.79) for 5ARI vs untreated. After excluding the first year after BPH diagnosis, adjusted HRs attenuated to 0.87 (0.79-0.97) for 5ARI vs ABs and 0.97 (0.87-1.08) for 5ARI vs untreated. Conclusion: Among men diagnosed with BPH, we found evidence of lower risks of subsequent prostate cancer in those treated with 5ARIs, but this appeared to be driven by cases diagnosed within a year of BPH, possibly reflecting prevalent prostate cancers that were initially misdiagnosed. After excluding the first year after BPH diagnosis, there was little evidence of a reduced prostate cancer risk in those taking 5ARIs.

(122) Erectile Hemodynamics Asessment In ED Patients With Self-Diagnosed Post-finasteride syndrome (PFS)

Abstract Introduction Much debate exists regarding the concept of PFS and its etiology. There exists data suggesting abnormal erectile hemodynamic alterations in this population. Objective This analysis was performed to define erectile hemodynamics in this population. Methods Patients attending the sexual medicine clinic at our institution presenting with (i) new onset ED after commencement of 5-ARI (ii) 5-ARI use specifically for hair loss (iii) with no prior ED history (iv) presenting ≥6 months after cessation of 5-ARI (v) and with at least 3 months use of 5-ARI (finasteride). All completed the IIEF EF domain questionnaire. B-mode assessment was conducted at 15MHz. Duplex ultrasound (PDDU) was conducted using a vasoactive agent-redosing schedule using trimix. On PDDU, a best quality erection (BQE) (equivalent to the best erection obtainable at home without erectogenic medication) was required for inclusion. Redosing was conducted if the patient failed to obtain a BQE up to a maximum of three doses. The criteria for normalcy on DUS included a peak systolic velocity (PSV) &amp;gt;30cms/s and an end-diastolic velocity (EDV) &amp;lt;5 cms/s. Results 141 men were included in the analysis. Mean patient age was 31±12 (18-42) years. All had used finasteride 1mg. Median vascular risk factor (VRF) number = 1 (0,1). Median duration of 5-ARI exposure = 16 (4, 46) months. Median duration off 5-ARI at first presentation to clinic = 11 (6, 28) months. No patients had ED prior to 5-ARI use. One third developed ED only after cessation of finasteride, at a mean duration off finasteride of 6±3 months. Median IIEF EFD score at presentation = 14 (6,18). Median (range) number of injections needed for BQE sufficiently suitable for DUS measurement was 2 (1, 3). Overall, mean PSV and EDV values were 60±18cm/s and 1.5±1.5 cm/s respectively. 29% required phenylephrine reversal before discharge from clinic. Conclusions These data suggest that hemodynamic alterations are not present in men complaining of ED with self-diagnosed PFS. Disclosure No

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 and MRI prostates: actively reducing prostate sizes and ambiguity

BackgroundMagnetic 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.MethodsFrom 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.Results351 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.ConclusionOur 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.

MP55-14 IsoPSA PERFORMANCE CHARACTERISTICS ARE NOT IMPACTED BY 5-ALPHA REDUCTASE INHIBITORS OR ALPHA-BLOCKERS

You have accessJournal of UrologyCME1 Apr 2023MP55-14 IsoPSA PERFORMANCE CHARACTERISTICS ARE NOT IMPACTED BY 5-ALPHA REDUCTASE INHIBITORS OR ALPHA-BLOCKERS Jason Scovell, Mark Stovsky, Aimee Kestranek, and Eric Klein Jason ScovellJason Scovell More articles by this author , Mark StovskyMark Stovsky More articles by this author , Aimee KestranekAimee Kestranek More articles by this author , and Eric KleinEric Klein More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003308.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: IsoPSA is a structure-based test linked to tumor biology that has demonstrated improved performance characteristics over PSA and percent free PSA to identify clinically actionable prostate cancer (GG2+). Medications for benign prostatic hyperplasia (BPH) including 5-α reductase inhibitors (5ARIs) and α-blockers are commonly used in the patient population undergoing prostate cancer screening. The relationship between 5-ARIs and PSA levels is well established. We sought to determine the impact that common BPH medications have on IsoPSA performance. METHODS: This is a secondary analysis of data from an institutional review board (IRB) approved, prospective, multicenter study evaluating IsoPSA in men≥50 years of age with a total PSA ≥ 4ng/ml with planned prostate biopsy who met previously described inclusion/exclusion criteria. Analytic groups included (i) all subjects, (ii-iii) +/- 5-ARI use, (iv-v) +/- α-blocker use. Sensitivity and specificity analysis were performed and receiver operating curves (ROC) were evaluated. RESULTS: A total of 1,385 men were recruited from a multi-center (8 sites), prospective, nonrandomized cohort with 888 men included in final analysis. Actionable prostate cancer, defined as GG2 or greater, was identified in a total of 316 patients (35.6%). In this cohort, 40 patients reported 5-ARI use and 217 reported α-blocker use. At the pre-determined IsoPSA threshold (5.25 all cancer; 6.0 GG2+) sensitivity to detect both all prostate cancer and actionable cancer was similar between all patients enrolled and patients on either 5-ARIs or α-blockers (All: 0.90 vs 5-ARI: 0.94 vs α-blocker: 0.85; p>0.05). Specificity was similar between patients regardless of 5-ARI (No 5-ARI: 0.46 vs 5-ARI: 0.45, p>0.05). Increased specificity was noted in patients on α-blockers (No α-blocker: 0.40 vs α-blocker: 0.61, p<0.05). There were no additional differences in FP, FN, FP, FN, LR (+/-), PPV, or NPV rates between all sub-cohorts. ROC analysis demonstrates excellent performance of IsoPSA regardless of 5-ARI or α-blocker use for both the detection of all prostate cancer and for actionable cancer (Figure 1). CONCLUSIONS: Common BPH medications (5-ARI and α-blockers) do not negatively impact IsoPSA performance characteristics for the detection of prostate cancer including clinically actionable prostate cancer. Source of Funding: Cleveland Diagnostics funded the initial study of IsoPSA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e769 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Scovell More articles by this author Mark Stovsky More articles by this author Aimee Kestranek More articles by this author Eric Klein More articles by this author Expand All Advertisement PDF downloadLoading ...

MP24-06 TNF-ALPHA INHIBITOR THERAPY SUPPRESSES GROWTH OF THE PROSTATE GLAND

You have accessJournal of UrologyCME1 Apr 2023MP24-06 TNF-ALPHA INHIBITOR THERAPY SUPPRESSES GROWTH OF THE PROSTATE GLAND Ra'ad Al-Faouri, Christina Sharkey, Leo L. Tsai, Zongwei Wang, and Aria F. Olumi Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Christina SharkeyChristina Sharkey More articles by this author , Leo L. TsaiLeo L. Tsai More articles by this author , Zongwei WangZongwei Wang More articles by this author , and Aria F. OlumiAria F. Olumi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003249.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies have established a relationship between prostate inflammation and the development of BPH. Steroid 5 alpha reductase type 2 (SRD5A2) is a pivotal enzyme in the development and growth of the prostate gland and the critical target for BPH therapy. We previously demonstrated that tumor necrosis factor alpha (TNF-a) regulates the epigenetic change of SRD5A2, leading to suppression of SRD5A2 gene and protein expression. However, little is known whether TNF-a inhibitor therapy affects prostatic growth. Here we aimed to evaluate the effect of TNF-a inhibitor therapy on the growth rate of prostate through analyzing the data of serial pelvic imaging scans. METHODS: In this retrospective cohort study, electronic records at Beth Israel Deaconess Medical Center were searched for men aged 18 and over who had serial pelvic Images (MRI or CT scans) while receiving TNF-a inhibitors. 99 men were included in the treatment cohort after applying exclusion criteria (TNF-a treatment duration <1 year, any pelvic/prostate surgery/radiation, use of 5ARIs, advanced prostate cancer, androgen deprivation therapy, testosterone therapy, poor image quality, or imaging interval <1 year). An age-matched cohort was constructed with the same inclusion/exclusion criteria but absent TNF-a therapy (n=99). The total prostate volume (TPV) was measured and calculated from baseline and follow-up imaging. Clinical data was collected for all men. RESULTS: There were no significant differences between the two groups in age, demographics, BMI or comorbidities. Mean baseline TPV was similar in the TNF-a inhibitor therapy group and control group (27.52±8.9 cc vs 27.3±9.6 cc, p-value: 0.71). For the entire cohort, the average imaging follow up duration was 3.79±0.32 years with no significant difference between the treatment and control groups. The median growth rate for men in the treatment cohort was significantly lower than those in the control group (-0.01 cc/year IQR= 1.2 compared to 0.68 cc/year IQR= 2.8, P-value 0.001). In a multiple regression model adjusting for age, race, initial TPV and BMI, men in the treatment group still had a significantly lower growth rate compared to the control group (-0.03 cc/year IQR: 0.82 vs 0.67 cc/year IQR: 0.93, p-value: 0.001). CONCLUSIONS: TNF-a inhibitors are negatively correlated with prostatic growth. Men with autoimmune diseases who are treated with TNF-a inhibitors may experience fewer urinary symptoms related to prostatic enlargement. Our study suggests that inflammatory mediators regulate prostatic growth. Source of Funding: NIH: R01DK124502 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e319 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ra'ad Al-Faouri More articles by this author Christina Sharkey More articles by this author Leo L. Tsai More articles by this author Zongwei Wang More articles by this author Aria F. Olumi More articles by this author Expand All Advertisement PDF downloadLoading ...