5-ARI Use Research Articles

5α-Reductase inhibitors and risk of high-grade or lethal prostate cancer.

5α-Reductase inhibitors (5ARIs) are widely used for benign prostatic hyperplasia despite controversy regarding potential risk of high-grade prostate cancer with use. Furthermore, the effect of 5ARIs on progression and prostate cancer death remains unclear. To determine the association between 5ARI use and development of high-grade or lethal prostate cancer. Prospective observational study of 38,058 men followed up for prostate cancer diagnosis and outcomes between 1996 and 2010 in the Health Professionals Follow-up Study. Use of 5ARIs between 1996 and 2010. Cox proportional hazards models were used to estimate risk of prostate cancer diagnosis or development of lethal disease with 5ARI use, adjusting for possible confounders including prostate specific antigen testing. During 448,803 person-years of follow-up, we ascertained 3681 incident prostate cancer cases. Of these, 289 were lethal (metastatic or fatal), 456 were high grade (Gleason sum [GS] 8-10), 1238 were GS 7, and 1600 were low grade (GS 2-6). A total of 2878 (7.6%) men reported use of 5ARIs between 1996 and 2010. After adjusting for confounders, men who reported ever using 5ARIs over the study period had a reduced risk of overall prostate cancer (hazard ratio [HR], 0.77; 95% CI, 0.65-0.91). 5ARI users had a reduced risk of GS 7 (HR, 0.67; 95% CI, 0.49-0.91) and low-grade (GS 2-6) prostate cancer (HR, 0.74; 95% CI, 0.57-0.95). 5ARI use was not associated with risk of high-grade (GS 8-10) prostate cancer (HR, 0.97; 95% CI, 0.64-1.46) or lethal disease (HR, 0.99; 95% CI, 0.58-1.69). Increased duration of use was associated with significantly lower risk of overall prostate cancer (HR for 1 year of additional use, 0.95; 95% CI, 0.92-0.99), localized (HR, 0.95; 95% CI, 0.90-1.00), and low-grade disease (HR, 0.92; 95% CI, 0.85-0.99). There was no association for lethal, high-grade, or grade 7 disease. While 5ARI use was not associated with developing high-grade or lethal prostate cancer, it was associated with a reduction in low-grade, GS 7, and overall prostate cancer. Because the number of patients with high-grade or lethal prostate cancer in our cohort was limited, we cannot rule out potential risk of harm with 5ARI use.

Nocturia improvement in the combination of Avodart(®) and tamsulosin (CombAT) study.

The purpose of the study was to assess the impact of dutasteride plus tamsulosin combination therapy, compared with dutasteride or tamsulosin monotherapy, on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) using data from the 4-year CombAT study. Nocturia was assessed using Question 7 of the International Prostate Symptom Score questionnaire. Efficacy measures included as follows: mean change in nocturia at 3-month intervals up to 48 months; proportion of patients with improvement/worsening in nocturia; nocturnal voiding frequency at baseline and study end, overall and by baseline subgroups; and nocturnal voiding frequency <2 at study end in patients with a baseline score ≥ 2. In total, 4,722 patients with a mean age of 66 years were included. Mean nocturia improvements were significantly superior (p ≤ 0.01) with combination therapy than with either monotherapy (adjusted mean change from baseline in IPSS Question 7 score at month 48: combination therapy -0.5, dutasteride -0.4, tamsulosin -0.3). Reduction in nocturia score with combination therapy was significantly (p ≤ 0.01) better than tamsulosin monotherapy across all baseline subgroups tested, except for men with previous 5ARI use. Among those with a baseline IPSS Q7 score ≥ 2, more patients with combination therapy had a score <2 at month 48 (34 %) compared with dutasteride (30 %, p = 0.018) or tamsulosin (26 %, p < 0.0001). Combination therapy provided greater improvements and less worsening of nocturia compared with both dutasteride and tamsulosin monotherapies. These analyses are the first to show greater improvement with a 5ARI/α-blocker combination versus either agent alone for the management of nocturia in patients with LUTS/BPH.

MP62-17 ASSESSMENT OF PREOPERATIVE 5-α REDUCTASE INHIBITOR USE AND PATHOLOGIC OUTCOMES AND BIOCHEMICAL RECURRENCE FREE SURVIVAL FOLLOWING RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized VII1 Apr 2014MP62-17 ASSESSMENT OF PREOPERATIVE 5-α REDUCTASE INHIBITOR USE AND PATHOLOGIC OUTCOMES AND BIOCHEMICAL RECURRENCE FREE SURVIVAL FOLLOWING RADICAL PROSTATECTOMY George R. Schade, Sarah K. Holt, William J. Ellis, Bruce L. Dalkin, Jonathan L. Wright, and Daniel W. Lin George R. SchadeGeorge R. Schade More articles by this author , Sarah K. HoltSarah K. Holt More articles by this author , William J. EllisWilliam J. Ellis More articles by this author , Bruce L. DalkinBruce L. Dalkin More articles by this author , Jonathan L. WrightJonathan L. Wright More articles by this author , and Daniel W. LinDaniel W. Lin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1974AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Two large randomized trials examining the 5-α reductase inhibitors (5ARI) finasteride and dutasteride for the chemoprevention of prostate cancer (PCa) demonstrated a possible association between 5ARI use and high-grade disease despite a decreased incidence of low-risk disease. These findings prompted us to evaluate the association between preoperative use 5ARI and pathologic findings and biochemical recurrence free survival (BCRFS) following radical prostatectomy (RP) at our institution. METHODS An IRB approved prospectively maintained institutional database was used to identify all patients taking 5ARI at the time of PCa diagnosis and prostatectomy. Men who received neoadjuvant androgen deprivation therapy were excluded. 5ARI exposed patients were matched 1:2 with control subjects by age, prostate volume, Gleason grade, and pathologic stage. Differences between groups were evaluated with Chi-squared test and t-tests where appropriate. The association between preop 5ARI use and BCRFS (PSA ≥0.2) was evaluated with the Kaplan-Meier method and a multivariable Cox-proportional hazards model. RESULTS A total of 46 5ARI eligible patients were identified and subsequently matched to 89 controls. Mean absolute PSA did not differ significantly between 5ARI users (7.53±0.91 ng/dL) and non-users (7.15± 048 ng/dL). Evaluated pathologic features, including positive surgical margins 15.22% vs 15.73% and mean cancer volume 2.61±0.47 vs 2.62±0.35 did not differ significantly between 5ARI users and non-users, respectively. At a mean follow-up of 2.8 years, there was a trend in 5-year BCRFS favoring 5ARI use (∼93%) vs non-users (75%) (p=0.09) (see figure) after controlling for age, PSA, Gleason score, pathologic stage, tumor size, and margins status. CONCLUSIONS Although preoperative use of 5ARI was not associated with worse pathologic features in this small retrospective matched-cohort study, the observed trend in improved BCFRS with 5ARI warrants further evaluation. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e724 Advertisement Copyright & Permissions© 2014MetricsAuthor Information George R. Schade More articles by this author Sarah K. Holt More articles by this author William J. Ellis More articles by this author Bruce L. Dalkin More articles by this author Jonathan L. Wright More articles by this author Daniel W. Lin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD26-03 IMPACT OF 5-ALPHA REDUCTASE INHIBITORS ON ENUCLEATION AND MORCELLATION EFFICIENCY DURING HOLMIUM LASER ENUCLEATION OF THE PROSTATE

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Surgical Therapy & New Technology I1 Apr 2014PD26-03 IMPACT OF 5-ALPHA REDUCTASE INHIBITORS ON ENUCLEATION AND MORCELLATION EFFICIENCY DURING HOLMIUM LASER ENUCLEATION OF THE PROSTATE Marawan M. El Tayeb, Naeem Bhojani, Jessica A. Mandeville, Ronald S. Boris, Lori D. Rawlings, Kimberly J. Smoot, and James E. Lingeman Marawan M. El TayebMarawan M. El Tayeb More articles by this author , Naeem BhojaniNaeem Bhojani More articles by this author , Jessica A. MandevilleJessica A. Mandeville More articles by this author , Ronald S. BorisRonald S. Boris More articles by this author , Lori D. RawlingsLori D. Rawlings More articles by this author , Kimberly J. SmootKimberly J. Smoot More articles by this author , and James E. LingemanJames E. Lingeman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2090AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The prostate is composed of approximately 70% glandular elements and 30% fibromuscular stroma. 5-alpha reductase inhibitors (5ARIs) are a commonly prescribed medication for BPH that reduces prostate volume by causing regression of the soft glandular element of the gland resulting in a greater % of the fibromuscular stromal element. HoLEP is an effective treatment for benign prostatic hyperplasia (BPH) that involves removal of the transitional zone. Due to the large volume of tissue accumulated during enucleation, morcellation is required for specimen removal. Enucleation and morcellation times are dependent on a number of factors including prostate volume as well as tissue quality. We hypothesized that patients taking 5ARIs prior to HoLEP may have longer surgeries secondary to a more challenging enucleation and/or morcellation due to the effect of these drugs on prostatic tissue. Factors potentially impacting tissue enucleation and morcellation were analyzed. METHODS A retrospective single institution analysis of HoLEP patients between 1998 and 2011 was performed. Variables that may impact enucleation and morcellation times were evaluated using univariate and multivariate linear regression models. RESULTS Overall, of 714 patients who underwent HoLEP, 222 or 31.1% of patients were taking a 5ARI (Table 1). After univariate and multivariate analysis, only the weight of the specimen that was removed was found to be predictive of enucleation and morcellation times (Tables 2 and 3). More specifically, with increasing prostate size there was a statistically significant increase in both enucleation and morcellation times. CONCLUSIONS On multivariate analysis only specimen weight significantly predicts enucleation and morcellation times. The use of 5ARIs as a predictor of enucleation and/or morcellation times was not found to be statistically significant. Table 1: Holmium laser enucleation of the prostate: patient characteristics 5 ARI (-) absent 5 ARI absent p N 492 222 Age (years) 70.6 (34-95) 70.3 (48-90) 0.6 PSA 7.7 (0.04-143.7) 6.9 (0.1-48) 0.3 Mean enucleation time (min) 67.1 (10-245) 66.2 (11-169) 0.7 Mean enculeation rate (g/min) 1.3 (0.01-8.1) 1.6 (0.2-5.1) 0.001 Mean morcellation time (min) 18.8 (0-260) 20.8 (0-91) 0.2 Mean morcellation rate (g/min) 5.5 (0.6-31.5) 5.6 (0.5-19.3) 0.8 Mean prostate weight (g) 80.0 (0.2-390.0) 94.7 (4.0-532.2) 0.001 Presence of cancer 50 18 Table 2: Univariate and multivariate analysis predicting enucleation and morcellation time Enucleation time Morcellation time Univariate Age 0.07 (p=0.05) 0.12 (p=0.001) PSA 0.10 (p=0.007) 0.24 (p<0.001) 5ARI -0.01 (p=0.7) 0.05 (p=0.2) Duration of 5ARI -0.01 (p=0.8) 0.02 (p=0-.7) Weight of specimen 0.3 (p<0.001) 0.7 (p<0.001) Presence of cancer -0.08 (p=0.04) -0.07 (p=0.06) Multivariate Age 0.04 (p=0.3) 0.02 (p=0.4) PSA -0.02 (p=0.6) -0.02 (p=0.4) 5ARI -0.05 (p=0.2) -0.04 (p=0.2) Weight of specimen 0.3 (p<0.001) 0.7 (p<0.001) Presence of cancer -0.05 (p=0.2) -0.005 (p=0.8) © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e759 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Marawan M. El Tayeb More articles by this author Naeem Bhojani More articles by this author Jessica A. Mandeville More articles by this author Ronald S. Boris More articles by this author Lori D. Rawlings More articles by this author Kimberly J. Smoot More articles by this author James E. Lingeman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical Effects of Discontinuing 5-Alpha Reductase Inhibitor in Patients With Benign Prostatic Hyperplasia

PurposeTo assess changes in lower urinary tract symptoms (LUTS), prostate volume, and serum prostate-specific antigen (PSA) after discontinuation of 5-alpha reductase inhibitor (5ARI) combination therapy in patients with benign prostatic hyperplasia (BPH).Materials and MethodsFrom December 2003 to December 2012, data were collected retrospectively from 81 men more than 40 years of age with moderate to severe BPH symptoms (International Prostate Symptom Score [IPSS]≥8). The men were classified into group 1 (n=42) and group 2 (n=39) according to the use of 5ARI therapy. A combination of dutasteride 0.5 mg with tamsulosin 0.2 mg was given daily to all patients for 1 year. For the next 1 year, group 1 (n=42) received the combination therapy and group 2 (n=39) received tamsulosin 0.2 mg monotherapy only. The IPSS, prostate volume, and PSA level were measured at baseline and at 12 and 24 months according to the use of dutasteride.ResultsDiscontinuation of dutasteride led to significant deterioration of LUTS, increased prostate volume, and increased PSA level. The repeated-measures analysis of variance showed that the changes in IPSS, prostate volume, and PSA level over time also differed significantly between groups 1 and 2 (p<0.001).ConclusionsWithdrawal of 5ARI during combination therapy resulted in prostate regrowth and deterioration of LUTS. The PSA level is also affected by the use of 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.

Finasteride Inhibits Human Prostate Cancer Cell Invasion through MMP2 and MMP9 Downregulation

IntroductionThe use of the 5-alpha reductase inhibitors (5-ARIs) finasteride and dutasteride for prostate cancer prevention is still under debate. The FDA recently concluded that the increased prevalence of high-grade tumors among 5-ARI-treated patients must not be neglected, and they decided to disallow the use of 5-ARIs for prostate cancer prevention. This study was conducted to verify the effects of finasteride on prostate cell migration and invasion and the related enzymes/proteins in normal human and tumoral prostatic cell lines.Materials and MethodsRWPE-1, LNCaP, PC3 and DU145 cells were cultivated to 60% confluence and exposed for different periods to either 10 µM or 50 µM finasteride that was diluted in culture medium. The conditioned media were collected and concentrated, and MMP2 and MMP9 activities and TIMP-1 and TIMP-2 protein expression were determined. Cell viability, migration and invasion were analyzed, and the remaining cell extracts were submitted to androgen receptor (AR) detection by western blotting techniques. Experiments were carried out in triplicate.ResultsCell viability was not significantly affected by finasteride exposure. Finasteride significantly downregulated MMP2 and MMP9 activities in RWPE-1 and PC3 cells and MMP2 in DU145 cells. TIMP-2 expression in RWPE-1 cells was upregulated after exposure. The cell invasion of all four tested cell lines was inhibited by exposure to 50 µM of finasteride, and migration inhibition only occurred for RWPE-1 and LNCaP cells. AR was expressed by LNCaP, RWPE-1 and PC3 cells.ConclusionsAlthough the debate on the higher incidence of high-grade prostate cancer among 5-ARI-treated patients remains, our findings indicate that finasteride may attenuate tumor aggressiveness and invasion, which could vary depending on the androgen responsiveness of a patient’s prostate cells.

Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alpha-reductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourable-risk prostate cancer. Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillance database. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method. The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-91.1) and 21.1 (range: 6-44.3) months, respectively. 5-ARIs significantly decreased PSADT compared to prior to their initiation. This effect may be due to preferential suppression of benign tissue following PSA nadir. The resulting PSADT would then represent a more accurate depiction of the true cancer-related DT. If validated with a larger cohort, 5-ARIs may enhance the utility of PSADT as a biomarker of disease progression in active surveillance.

Increased population use of medications for male lower urinary tract symptoms/benign prostatic hyperplasia correlates with changes in indications for transurethral resection of the prostate

Objective. The aim of this study was to determine whether there are correlations between medication use for lower urinary tract symptoms/benign prostate hypertrophy (LUTS/BPH) and alteration in incidence and indications for transurethral resection of the prostate (TURP). Material and methods. The number of TURP patients between 1984 and 2008 in Iceland was obtained from hospital registries. The number of defined daily doses (DDDs) of 5-alpha-reductase inhibitors (5aRIs) and alpha-blockers (ABs) sold was obtained from the Icelandic Medicines Control Agency. Charts of all surgical BPH patients in Iceland from 1998 to 2008 were retrospectively reviewed. The main outcomes measures were: DDDs sold of 5aRIs and ABs, total numbers of TURP, indications for TURP and complications. Results. After the introduction of ABs and 5aRIs, sales increased annually at a near linear rate. TURP rates peaked in 1992, then declined. In 2008, 81 and 3.4 of 1000 men over the age of 50 used LUTS/BPH medications or underwent TURP, respectively. There was an inverse correlation between LUTS/BPH medication use and (i) overall TURP (R2 = 0.85), (ii) TURP done for absolute indications (R2 = 0.91), and (iii) LUTS with (R2 = 0.77) and (iv) without previous medical therapy (R2 = 0.75). As medication use rose, fewer TURPs were performed for previous history of urinary retention, and more for recurrent urinary tract infections. Conclusion. Increased use of ABs and 5aRIs in the Icelandic population correlated with decreasing incidences of TURP procedures for both LUTS and absolute indications. The sequelae of BPH and indications for TURP are changing as medication use increases, although a clear causative link is hard to establish.

Use of 5α-reductase inhibitors for lower urinary tract symptoms and risk of prostate cancer in Swedish men: nationwide, population based case-control study

Objective To assess the association between 5α-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk.Design Nationwide, population based case-control study for men diagnosed with...

1941 5 α REDUCTASE INHIBITORS AND RISK OF PROSTATE CANCER. NATION-WIDE, POPULATION-BASED CASE-CONTROL STUDY

You have accessJournal of UrologyProstate Cancer: Detection & Screening (III)1 Apr 20131941 5 α REDUCTASE INHIBITORS AND RISK OF PROSTATE CANCER. NATION-WIDE, POPULATION-BASED CASE-CONTROL STUDY David Robinson, Hans Garmo, Anna Bill-Axelson, Lorelei Lorelei, Lars Holmberg, and Pär Stattin David RobinsonDavid Robinson Umeå, Sweden More articles by this author , Hans GarmoHans Garmo London, United Kingdom More articles by this author , Anna Bill-AxelsonAnna Bill-Axelson Uppsala, Sweden More articles by this author , Lorelei LoreleiLorelei Lorelei Boston, MA More articles by this author , Lars HolmbergLars Holmberg Uppsala, Sweden More articles by this author , and Pär StattinPär Stattin Umeå, Sweden More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2360AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Results from two randomized clinical trials have raised concern about an increased risk of high grade prostate cancer in men on 5 α-reductase inhibitors (5-ARI). We assessed the association between 5-ARI use in men with lower urinary tract symptoms (LUTS) and prostate cancer risk. METHODS A case-control study for men diagnosed with prostate cancer 2007 to 2009 within Prostate Cancer data Base Sweden (PCBaSe) 2.0. was performed. Information from The National Prostate Cancer Register, The Patient Register, The Census, and The Prescribed Drug Register in Sweden with data on 5-ARI use prior to date of diagnosis. Cases and five controls per case randomly selected from matched men in the background population, in total 26 735 cases and 133 671 matched controls were included.Odds ratios (OR) of prostate cancer and 95% confidence intervals (95% CI) from conditional logistic regression analyses were retrived. RESULTS A total of 1499 men had been exposed to 5-ARI prior to prostate cancer diagnosis, 412 of these men had a prostate cancer with a Gleason score 8-10. There was a steady decrease in risk of prostate cancer overall for an increasing duration of exposure, down to OR 0.72 (95% CI 0.59-0.89) ptrend <0.0001, in men on 5-ARI for more than three years. This decrease was strongest for Gleason score 2–6 cancers down to OR 0.27 (95% CI 0.15-0.48) ptrend <0.0001 whereas OR for Gleason score 7 tumors was 0.79 (95% CI 0.57-1.10) ptrend=0.0004. In contrast, the risk of Gleason score 8-10 tumors did not decrease with increasing exposure time, OR 0.96 (95% CI=0.83-1.11) for 0-1 year of exposure, OR 1.07 (95% CI=0.88-1.31) for 1–2 years, OR 0.96 (95% CI=0.72–1.27) for 2–3 years and OR 1.23 (95% CI=0.90-1.68) for more than 3 years of exposure, ptrend = 0.46. CONCLUSIONS Men treated with 5-ARI for LUTS had a decreased risk of Gleason score 2–7, and no evidence of an increased risk of Gleason score 8-10 prostate cancer. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e795-e796 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Robinson Umeå, Sweden More articles by this author Hans Garmo London, United Kingdom More articles by this author Anna Bill-Axelson Uppsala, Sweden More articles by this author Lorelei Lorelei Boston, MA More articles by this author Lars Holmberg Uppsala, Sweden More articles by this author Pär Stattin Umeå, Sweden More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

143 TRENDS AND VARIATION IN MEDICAL MANAGEMENT OF MEN WITH BENIGN PROSTATIC HYPERPLASIA AND LOWER URINARY TRACT SYMPTOMS (1993-2010)

INTRODUCTION AND OBJECTIVES: Management options for men with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) have evolved over the last 15 years. We used a population-based survey to describe historical trends and variation in medical management of men with BPH/LUTS in the United States. METHODS: We used the National Ambulatory Medical Care Survey (1993-2010) to evaluate outpatient office visits by men with BPH/LUTS. Visits for BPH/LUTS were based on ICD-9 diagnosis codes for BPH and/or patient self-report of LUTS. Prescriptions of interest included -blockers (AB), 5reductase inhibitors (5ARI), and anticholinergics (AC). Standardized survey weights were applied to obtain national estimates. Data from multiple years were occasionally combined to ensure statistical reliability. Linear trends over time were analyzed using 2 tests. Factors associated with AB use were evaluated with 2 tests and multivariable logistic regression. All tests were performed to the 5% level of significance. RESULTS: From 1993-2010, there were over 141 million outpatient visits for men with BPH/LUTS. Among these visits, ABs were prescribed most commonly, increasing from 6.4% of visits in 1993 to nearly 30% in 2010 (p 0.01). Use of 5ARIs increased from 3.8% of visits in 1993-1994 to 14.3% of visits in 2009-2010 (p 0.01). Use of ACs also increased, from 2.3% of visits in 1999-2000 to 8.2% of visits in 2009-2010. Use of terazosin decreased from 78% of AB prescriptions from 1993-1995 to 12% from 2008-2010 (Figure). In the modern era, tamsulosin was the most common AB prescribed, representing 61% of prescriptions from 2008-2010 (Figure). Use of AB did not vary by race, region, or insurance status (all p 0.05). Compared to primary care physicians, urologists were no more likely to prescribe ABs prior to the introduction of tamsulosin (OR 0.88, 95% CI 0.57-1.35). However, after tamsulosin was available, urologists were nearly twice as likely to prescribe ABs (OR 1.92, 95% CI 1.41-2.62). CONCLUSIONS: Over the past 15 years, there has been a steady increase in use of medications to manage men with BPH. Urologists were more likely to prescribe ABs after tamsulosin was available, suggesting that urologists may adopt novel medications more readily that primary care providers. Source of Funding: NIH T32 Clinical Training Grant.

Editorial Comment

The use of 5-ARIs in men undergoing active surveillance for low-risk PCa has been controversial. This study adds data that 5-ARI therapy could be beneficial. The results are consistent with those from the REDEEM trial in that a significant majority (75%) of men receiving 5-ARI had no evidence of pathologic cancer progression at the restaging biopsy after a median follow-up of 35 months. Active Surveillance of Very-low-risk Prostate Cancer in the Setting of Active Treatment of Benign Prostatic Hyperplasia With 5α-reductase InhibitorsUrologyVol. 81Issue 5PreviewTo review the efficacy of treating benign prostatic hyperplasia and very-low-risk prostate cancer (PCa) in patients receiving active surveillance and 5α-reductase inhibitor (5-ARI; finasteride or dutasteride) treatment. Full-Text PDF ReplyUrologyVol. 81Issue 5PreviewConsistent with the findings from the REDEEM trial, our outcomes suggest that 5-ARIs do not increase the risk of intermediate- or high-risk PCa (Gleason score 7-10) in men receiving active surveillance. Our study demonstrates only a small risk of progression to Gleason score 7 cancer on repeat biopsy. We believe this can be attributed to detection bias, as the gland volume reduction from 5-ARI therapy—along with the simple increase in total cumulative number of biopsy cores taken over time—enhances the clinician's ability to find higher grade PCa. Full-Text PDF

Reply

Consistent with the findings from the REDEEM trial, our outcomes suggest that 5-ARIs do not increase the risk of intermediate- or high-risk PCa (Gleason score 7-10) in men receiving active surveillance. Our study demonstrates only a small risk of progression to Gleason score 7 cancer on repeat biopsy. We believe this can be attributed to detection bias, as the gland volume reduction from 5-ARI therapy—along with the simple increase in total cumulative number of biopsy cores taken over time—enhances the clinician's ability to find higher grade PCa. Editorial CommentUrologyVol. 81Issue 5PreviewThe use of 5-ARIs in men undergoing active surveillance for low-risk PCa has been controversial. This study adds data that 5-ARI therapy could be beneficial. The results are consistent with those from the REDEEM trial in that a significant majority (75%) of men receiving 5-ARI had no evidence of pathologic cancer progression at the restaging biopsy after a median follow-up of 35 months. Full-Text PDF

Current Status of 5α-Reductase Inhibitors in Prostate Disease Management

The key enzyme in the androgen synthesis and androgen receptor pathways is 5α-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia.

Canadian Consensus Conference: The FDA decision on the use of 5ARIs

Canadian Consensus Conference: The FDA decision on the use of 5ARIs

PCPT, MTOPS and the use of 5ARIs: a Canadian consensus regarding implications for clinical practice

Two large, recently published, definitive trials evaluated the benefits of 5-alpha reductase inhibitors (5ARIs). The Prostate Cancer Prevention Trial (PCPT) tested the effect of finasteride for prostate cancer prevention and the Medical Therapy of Prostatic Symptoms (MTOPS) tested its effect in benign prostatic hyperplasia (BPH). Both trials were strongly positive. However, the role of 5ARIs in the clinical management of patients remains controversial. The consensus conference, which forms the basis for this report, attempted to develop an expert opinion, based on these studies, as to the optimal use of 5ARIs in patient management. The Canadian Consensus Meeting, organized by the Canadian Urology Research Consortium and the Canadian Urologic Oncology Group, held in Toronto on May 7, 2006, focused on the new data from the PCPT and the MTOPS study. Internationally recognized experts and clinicians discussed the implications of these data on clinical practice and issued a recommendation on the optimal management of patients with BPH. The Consensus meeting agreed on the following recommendations: The overall results from the PCPT and MTOPS studies are of importance to the urologic, as well as to the greater medical, community.Prostate management guidelines should be updated to include the results from both the MTOPS and the PCPT studies.In the PCPT, the incidence of high-grade cancer was higher in the finasteride-treated group (6.4%), compared with the placebo group (5.1%). Subsequent analyses strongly suggest that this increased prevalence was owing to a detection bias caused by the reduction in prostate volume in patients taking finasteride, compared with patients taking placebo. This resulted in an improved detection at biopsy of high-grade cancer in the finasteride group.In men who have large prostates and lower urinary tract symptoms (LUTS), 5ARIs( section sign) should be considered, both for the treatment of BPH and for prostate cancer risk reduction.For men who are concerned about prostate cancer, it is appropriate to discuss chemoprevention with finasteride.Urologists are encouraged to disseminate these recommendations among other healthcare professionals.

Major role for 5-alpha reductase inhibitors in the aging male

The Canadian consensus meeting, held in Toronto in May 2006, represents an important initiative in sorting out much of the confusion surrounding the use of 5-alpha reductase inhibitors (5ARIs) in clinical practice. The impact of the Medical Therapy of Prostatic Symptoms study and the Prostate Cancer Prevention Trial (PCPT) are quite dramatic as they confirm that 5ARIs, a class of drugs that never gained much market share in urologic practice, have significant impact on both benign prostatic hyperplasia (BPH) and prostate cancer- related outcomes. It is quite ironic that these pivotal trials, funded not by industry but by tax payers, have come to fruition at a time when finasteride is soon to be genericized in the United States. Commercial interests aside, this consensus summary provides useful information for urologists and primary care physicians. With respect to BPH-related outcomes, the 5ARIs have clearly demonstrable benefits in reducing long-term complications and lower urinary tract symptoms (LUTS). There is little debate on this topic. The impact of 5ARIs on prostate cancer prevention remains controversial and, in my mind, these recommendations have some limitations that deserve mention. With respect to the grade and volume bias, this observation, internationally led by our group, is real, and many other centres are now reporting it. We must emphasize that these recommendations report that this bias explains the PCPT grade issue “with a high degree of confidence.” While I truly believe this is the case, a small but lingering doubt must still exist within us all. It is essentially now unprovable! Perhaps more relevant than the grade issue is the clinical significance of the prevented cancers. Indeed, in the PCPT the relative risk reduction in “for-cause” biopsies, those that mirror clinical practice, is only 10%. I believe that future pivotal trials, such as REDUCE (the Reduction by Dutasteride of Prostate Cancer Events study; dutasteride v. placebo among men with negative prostate biopsy and elevated prostate-specific antigen), will help us clarify some of these issues. With respect to class effect and use of 5ARIs, I believe that both 5ARIs are good agents and that there are theoretical advantages to dutasteride in cancer prevention. Further trials will bear this out. What are clinicians to do? Consider the cancer prevention properties as an added benefit to complication reduction and symptom improvement for men with large-volume BPH and LUTS. In my view, either 5ARI is appropriate. Consider primary prevention with 5-ARI in ultra-high risk men, those in whom a cancer is likely to be clinically significant (e.g., men with strong family history, African-Canadians or both). In this setting, the best evidence would support the use of finasteride.

Inhibitors of 5α-reductase-related side effects in patients seeking medical care for sexual dysfunction.

Despite their efficacy in the treatment of benign prostatic hyperplasia (BPH) the popularity of inhibitors of 5α-reductase (5ARI) is limited by their association with adverse sexual side effects. However, the real impact of 5ARI on sex hormones and sexual function is controversial. To investigate the role of 5ARI therapy on hormonal parameters and sexual function in men already complaining of sexual problems. A consecutive series of 3837 men (mean age 63.5±12.8 yr) attending our outpatient clinic for sexual dysfunction was retrospectively studied. Several clinical, biochemical, and instrumental (penile color doppler ultrasound) factors were evaluated. Among the patients studied, 78.7% reported erectile dysfunction, 51.1% hypoactive sexual desire (HSD), 86.7% perceived reduced sleep-related erections (PR-SRE) and 19.1% premature ejaculation. The use of 5ARI was associated with an increased risk of HSD and PR-SR whereas no relationship was found with erectile dysfunction and ejaculation disturbances. Subjects using 5ARI also more frequently had gynecomastia along with reduced SHBG and higher calculated free testosterone levels. All these associations were confirmed in a case-control study comparing 5ARI users with age-body mass index-smoking status and total testosterone-matched controls. Our data indicates that use of 5ARI in men with sexual dysfunction does not significantly exacerbate pre-existing ejaculatory or erectile difficulties, but can further impair their sexual life by reducing sexual drive and spontaneous erection.

A Population-Based Nested Case-Control Study in Taiwan: Use of 5α-Reductase Inhibitors Did Not Decrease Prostate Cancer Risk in Patients with Benign Prostate Hyperplasia

5α-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00-3.59; overall cancer: OR = 1.51; 95% CI: 1.00-2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17-80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride.

Canadian Consensus Conference: The FDA decision on the use of 5ARIs.

Canadian Consensus Conference: The FDA decision on the use of 5ARIs.