Risk of age-related macular degeneration in men receiving 5α-reductase inhibitors: a population-based cohort study.

BACKGROUND: Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration. OBJECTIVE: To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin. DESIGN: Retrospective, population-based cohort study using new-user and active-comparator design. SETTING: General population. SUBJECTS: Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018. METHODS: Data were extracted from Taiwan's National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs. RESULTS: We included 13 586 5ARIs users (mean age: 69 years) and 54 344 tamsulosin users (mean age: 68.37 years). After a mean follow-up of 3.7 years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98-1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02-1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87-1.12], in the subgroup analyses. CONCLUSIONS: We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence.

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

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

Long-term efficacy and safety of dutasteride 0.5 mg in Korean men with androgenetic alopecia: 5-year data demonstrating clinical improvement with sustained efficacy.

Dutasteride 0.5 mg is a dual inhibitor of 5α-reductase type I and II and was approved in Korea in 2009 for treating androgenetic alopecia (AGA) in men. We investigated the 5-year efficacy and safety of dutasteride 0.5 mg in Korean men with AGA using the basic and specific (BASP) classification. This retrospective analysis included 99 male AGA patients aged ≥18 years who were treated with dutasteride 0.5 mg for at least 5 years from October 2009 to December 2016 at Kyung Hee University Hospital in Gangdong. Patient photographs were scored using the BASP classification, and the Investigator Global Assessment (IGA) was performed using a seven-point scale. Patient improvement (IGA score ≥1) and prevention of disease progression (IGA score ≥0) were 89.9% (89/99) and 93.9% (93/99), respectively. According to the BASP classification, 52.5% (52/99) of the basic type, 75% (15/20) of the specific F type, and 82.2% (60/73) of the specific V type showed clinical improvement after 5 years of treatment. Dutasteride demonstrated long-term safety and efficacy in Korean male patients with AGA over a period of at least 5 years, with results comparable to those of other long-term efficacy studies of finasteride 1 mg in male patients with AGA.

Dutasteride in the treatment of frontal fibrosing alopecia: Systematic review and meta-analysis.

Frontal fibrosing alopecia (FFA) is a scarring alopecia with fronto-temporo-parietal hairline recession. Although no proven treatment for FFA exists, dutasteride has been suggested as a potential treatment option. We aimed to evaluate the therapeutic response of oral dutasteride in FFA patients. The identification and selection of studies were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 criteria. To assess the risk of bias for each study, we used the Cochrane's risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool. A random effects model meta-analysis was performed. Estimated proportion of stabilization for eligible studies was calculated to evaluate the effectiveness of dutasteride for treating FFA. Among patients who achieved stabilization, subgroup analysis was conducted on those showing improvement. Seven studies including 366 patients who received oral dutasteride were identified. The estimated proportion of patients who experienced stabilization of FFA with oral dutasteride was 0.628 (95% CI: 0.398-0.859). In subgroup analyses of patients who experienced improvement, the estimated proportion of improvement was 0.356 (95% CI: 0.163-0.549). In this systematic review and meta-analysis, oral dutasteride revealed to be a good treatment option for disease stabilization or improvement in patients with FFA.

Serum Testosterone and Dihydrotestosterone and Incidence and Progression of Lower Urinary Tract Symptoms: Results From the REDUCE Study.

PURPOSE: Though the pathogenesis of benign prostatic hyperplasia is unclear, it was previously believed that increasing androgen levels contributed, though not all data support this idea. We tested if elevated serum testosterone or dihydrotestosterone were risk factors for lower urinary tract symptoms incidence in asymptomatic men and for lower urinary tract symptoms progression in symptomatic men. MATERIALS AND METHODS: A post hoc analysis of REDUCE was performed in 3009 asymptomatic men and in 2145 symptomatic men. REDUCE was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated prostate-specific antigen and negative prestudy biopsy. We estimated multivariable adjusted hazard ratios and 95% confidence intervals using Cox models to test the association between quintiles of serum testosterone and dihydrotestosterone at baseline and lower urinary tract symptoms incidence and progression and tested for interaction by treatment arm (dutasteride vs placebo). RESULTS: In asymptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms incidence (P = .9, P = .4). In symptomatic men, there was no evidence serum testosterone or dihydrotestosterone were related to lower urinary tract symptoms progression (P = .9, P = .7). Results were similar in both placebo and dutasteride arms (all P interaction ≥ .3). CONCLUSIONS: In REDUCE, higher serum testosterone and higher serum dihydrotestosterone were not associated with either lower urinary tract symptoms incidence in asymptomatic men or lower urinary tract symptoms progression in symptomatic men. These data do not support the hypothesis that serum androgens in middle-aged men are associated with lower urinary tract symptoms.

The Effect Of Continuously Dutasteride Monotherapy on The Expression Of Protein Kinase C-Alpha Enzyme In BPH Model Of Wistar Strain Rattus Novergicus Rat.

Background: Benign prostate hyperplasia (BPH) is frequently found in the elderly and significantly impacts the quality of life. One of the risk factors that induce BPH is the androgen hormone. One of the effective medications in reducing the severity of Lower Urinary Tract Symptoms caused by BPH is the α-adrenergic receptor 5α-reductase inhibitor. Objective: The study aims to see the effect of long-term dutasteride on the expression of the PKC-α enzyme in prostatic stromal tissue in the BPH Model of Wistar strain Rattus norvegicus rats. Method: This study was an experimental, post-test-only, control group design that used randomization in sample selection. The objective is to measure the expression of PKC-α enzyme from prostate tissue of an adult male Wistar Strain of Rattus Novergicus rat that was given testosterone to induce BPH and given dutasteride in 1,3 and 6 days continuously. Data is shown in mean±SD, and all of the data were analyzed using the software SPSS 21st version with the One Way ANOVA Statistical method after fulfilling the normality test and variant homogeneity test. Data analysis with confidence rate 95% and a=0,05. Results: There was a decrease of PKC-α enzyme and prostate weight in dutasteride monotherapy in 1,3,6 days compared to the positive control, and the lowest value was on the sixth day (SD ± 2876.8). There was a constant decrease of PKC-α enzyme from the first day until the sixth day. Conclusion: In conclusion, long-term dutasteride monotherapy could significantly decrease the level of PKC-α enzyme. There was no upregulation of the PKC-α enzyme in the long term of dutasteride monotherapy.

Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro.

Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)-generally used for treatment of benign prostatic enlargement-and lovastatin (Lova)-a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 µM Duta and ≥1 µM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 µM Duta + 0.5 µM Lova or 0.5 µM Duta + 1 µM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).

Intradermal Delivery of Alopecia Therapeutics: Current State and Future Prospects.

BACKGROUND: Mesotherapy, a technique of transdermal microinjections of specific preparations, is increasingly used in fields such as dermatology and specifically for alopecia treatment. Its popularity stems from its ability to deliver drugs in a targeted manner while minimizing systemic side effects. OBJECTIVE: To assess and review current knowledge regarding the use of mesotherapy to deliver alopecia medications and highlight future directions for research. MATERIALS AND METHODS: The authors used research databases including PubMed and Google Scholar to identify current literature on mesotherapy and alopecia. The following search terms were used among other terms: "Mesotherapy" or "Intradermal" AND "Alopecia". RESULTS: Recent studies are promising for the intradermal delivery of dutasteride and minoxidil in the treatment of androgenetic alopecia. CONCLUSION: Although limitations exist with dutasteride and minoxidil therapies, further research regarding the preparation, delivery, and maintenance of these drugs is warranted as mesotherapy could establish this technique as a safe, effective, and viable treatment option for androgenetic alopecia.

Effects of dutasteride and tamsulosin on penile morphology in a rodent model.

PURPOSE: To evaluate the penile morphology after the isolated and combined administration of dutasteride and tamsulosin in a rodent model. MATERIALS AND METHODS: Forty male rats were assigned into the following groups: Control group (C, receiving distilled water, n=10); Dutasteride group (D, receiving 0.5 mg/Kg/day of dutasteride, n=10); Tamsulosin group (T, receiving 0.4 mg/Kg/day of tamsulosin, n=10); and Dutasteride associated with Tamsulosin group (DT, receiving both drugs n = 10). All drugs were administered via oral gavage. After 40 days, the animals were submitted to euthanasia and their penises were collected for histomorphometric analyses. Data were compared using one-way ANOVA followed by Bonferroni's post-test, considering p<0.05 as significant. RESULTS: The sinusoidal space and smooth muscle fiber surface densities (Sv), and the cross-sectional penile areas of rats in groups D, T and DT were reduced in comparison to controls with the most notable reductions in the combined therapy group. The connective tissue and elastic system fibers Sv were augmented in groups D, T and DT in comparison with the control group, again with the most pronounced changes observed in animals receiving the combined therapy. CONCLUSION: Both treatments with dutasteride or tamsulosin promoted penile morphometric modifications in a rodent model. The combination therapy resulted in more notable modifications. The results of this study may help to explain the erectile dysfunction observed in some men using these drugs.

Smoking and lower urinary tract symptoms in Reduction by Dutasteride of Prostate Cancer Events Trial.

BACKGROUND: Benign prostatic hyperplasia is common in older men, with many developing lower urinary tract symptoms (LUTS) that impair quality of life. Smoking has many well-established adverse effects, but its effects on benign prostatic hypertrophy (BPH) and associated LUTS are unclear. We sought to determine if smoking is a risk factor for the incidence of LUTS in asymptomatic men and for the progression of LUTS in symptomatic men. METHODS: We performed a post-hoc analysis of Reduction by Dutasteride of Prostate Cancer Events in 3060 "asymptomatic" men with baseline International Prostate Symptom Score (IPSS) < 8 and in 2198 symptomatic men with baseline IPSS ≥ 8 not taking 5α-reductase inhibitors or α-blockers. We used multivariable Cox regression models to assess associations between smoking status at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first report of medical or surgical treatment for BPH, or sustained clinically significant LUTS (two reports of IPSS > 14). Among symptomatic men, LUTS progression was defined as IPSS increase of ≥4 points from baseline, surgical intervention for BPH, or starting a new BPH drug. RESULTS: Of 3060 asymptomatic men, 15% (n = 467) were current, 40% (n = 1231) former, and 45% (n = 1362) never-smokers. Of 2198 symptomatic men, 14% (n = 320) were current, 39% (n = 850) former, and 47% (n = 1028) never-smokers. In asymptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with LUTS incidence (adjusted hazard ratio [adj-HR] = 1.08; 95% confidence interval [95% CI]: 0.78-1.48 and adj-HR = 1.01; 95% CI: 0.80-1.30). In symptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with the progression of LUTS (adj-HR = 1.11; 95% CI: 0.92-1.33 and adj-HR = 1.03; 95% CI: 0.90-1.18). CONCLUSIONS: In REDUCE, smoking status was not associated with either incident LUTS in asymptomatic men or progression of LUTS in symptomatic men.

Evaluation of sexual function after dutasteride treatment in patients with once-negative prostate biopsy and benign prostate hyperplasia.

INTRODUCTION: Patients with benign prostatic hyperplasia are usually treated with 5α-reduced inhibitors (5ARIs) such as finasteride and dutasteride. However, studies on the influence of 5ARIs on sexual function have been controversial. In this study, we evaluated the impact of dutasteride treatment for erectile function in patients with once-negative prostate biopsy and benign prostate hyperplasia. PATIENTS AND METHODS: 81 patients with benign prostate hyperplasia were enrolled in a one-armed prospective study. They were administrated 0.5 mg/day of dutasteride for 12 months. Patient characteristics and changes of International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF)-15 scores at baseline and 12 months after dutasteride administration were examined. RESULTS: The mean ± standard deviation (SD) age of the patients was 69.4 ± 4.9 years and the prostate volume was 56.6 ± 21.3 mL, respectively. The mean ± SD prostate volume and PSA levels were decreased 25.0 and 50.9%, respectively, after 12 months of dutasteride administration. IPSS total, voiding subscore, storage subscore, and quality of life score significantly improved after 12 months of dutasteride administration. No statistically significant change in IIEF-total score from 16.3 ± 13.5 to 18.8 ± 16.0 (p = 0.14), IIEF-EF score from 5.1 ± 6.9 to 6.4 ± 8.3 (p = 0.13) were observed. There was no decrease in erectile function severity. CONCLUSION: Twelve months administration of dutasteride for patients with BPH improved urinary function and did not increase the risk of sexual dysfunction.

Pregnenolone for the treatment of L-DOPA-induced dyskinesia in Parkinson's disease.

Growing preclinical and clinical evidence highlights neurosteroid pathway imbalances in Parkinson's Disease (PD) and L-DOPA-induced dyskinesias (LIDs). We recently reported that 5α-reductase (5AR) inhibitors dampen dyskinesias in parkinsonian rats; however, unraveling which specific neurosteroid mediates this effect is critical to optimize a targeted therapy. Among the 5AR-related neurosteroids, striatal pregnenolone has been shown to be increased in response to 5AR blockade and decreased after 6-OHDA lesions in the rat PD model. Moreover, this neurosteroid rescued psychotic-like phenotypes by exerting marked antidopaminergic activity. In light of this evidence, we investigated whether pregnenolone might dampen the appearance of LIDs in parkinsonian drug-naïve rats. We tested 3 escalating doses of pregnenolone (6, 18, 36 mg/kg) in 6-OHDA-lesioned male rats and compared the behavioral, neurochemical, and molecular outcomes with those induced by the 5AR inhibitor dutasteride, as positive control. The results showed that pregnenolone dose-dependently countered LIDs without affecting L-DOPA-induced motor improvements. Post-mortem analyses revealed that pregnenolone significantly prevented the increase of validated striatal markers of dyskinesias, such as phospho-Thr-34 DARPP-32 and phospho-ERK1/2, as well as D1-D3 receptor co-immunoprecipitation in a fashion similar to dutasteride. Moreover, the antidyskinetic effect of pregnenolone was paralleled by reduced striatal levels of BDNF, a well-established factor associated with the development of LIDs. In support of a direct pregnenolone effect, LC/MS-MS analyses revealed that striatal pregnenolone levels strikingly increased after the exogenous administration, with no significant alterations in downstream metabolites. All these data suggest pregnenolone as a key player in the antidyskinetic properties of 5AR inhibitors and highlight this neurosteroid as an interesting novel tool to target LIDs in PD.

The Effect of Tamsulosin, Dutasteride Monotherapy and Tamsulosin-Dutasteride Combination on Prostate Smooth Muscle Contractility in BPH Model Wistar Strain Rattus Novergicus.

Background: Following the c In the management of BPH, Tamsulosin is an example of a-adrenergic receptor blocker drug that is usually used. In addition, dutasteride is also a BPH drug that works as a group of 5 a reductase inhibitor. However, the weakness of long-term administration of a1-adrenergic receptor antagonists can result in upregulation of prostate smooth muscle cell contractility and expression of a-adrenergic mRNA receptors, resulting in hyperactivity and supersensitivity to a-agonists. Objective: Our study aimed to determine the effect of long-term administration of tamsulosin, dutasteride and tamsulosin-dutasteride combination on the contractility of prostate smooth muscle cells in BPH model rats. Methods: This study was designed using an experimental post test only method, control group design. It measured the contractility of prostate smooth muscle cells from samples obtained from the prostatic stroma of experimental animals adult male Rattus norvegicus Wistar strain induced BPH and administered tamsulosin 1 mg/kg/day, dutasteride 0.5 mg/kg/day, and a combination of continuous administration for 1, 6 and 12 consecutive days. Data were analyzed using one way ANOVA if the data distribution was normal or Kruskall Walis if the data distribution was abnormal. Result: The effect of tamsulosin, dutasteride and the combination of tamsulosin with dutasteride on prostate smooth muscle cell contractility in experimental animals Rattus norvegicus Wistar strain showed that tamsulosin administration for six days, twelve days, and the combination of tamsulosin dutasteride for one day got statistically significant different result (p=0.016; p=0.006; p=0.029) compared to the negative control group. In addition, there was a difference between the tamsulosin and dutasteride combination group for 12 days compared to tamsulosin monotherapy for 6 days and 12 days (p=0.160; p=0.010). Conclusion: Continuous administration of monotherapy tamsulosin has an upregulation effect on the sixth to twelfth day. Decreased contractility of prostate smooth muscle cells occurs on the first day but will increase on the sixth to twelfth day. On the other hand, the results of our study also showed that the combination of tamsulosin and dutasteride gave the effect of reducing contractility and was most effective on day 12.

Androgenetic alopecia in transgender and gender diverse populations: A review of therapeutics.

Androgenetic alopecia (AGA) management is a significant clinical and therapeutic challenge for transgender and gender-diverse (TGD) patients. Although gender-affirming hormone therapies affect hair growth, there is little research about AGA in TGD populations. After reviewing the literature on approved treatments, off-label medication usages, and procedures for treating AGA, we present treatment options for AGA in TGD patients. The first-line treatments for any TGD patient include topical minoxidil 5% applied to the scalp once or twice daily, finasteride 1 mg oral daily, and/or low-level laser light therapy. Spironolactone 200 mg daily is also first-line for transfeminine patients. Second-line options include daily oral minoxidil dosed at 1.25 or 2.5 mg for transfeminine and transmasculine patients, respectively. Topical finasteride 0.25% monotherapy or in combination with minoxidil 2% solution are second-line options for transmasculine and transfeminine patients, respectively. Other second-line treatments for any TGD patient include oral dutasteride 0.5 mg daily, platelet-rich plasma, or hair restoration procedures. After 6-12 months of treatment, AGA severity and treatment progress should be assessed via scales not based on sex; eg, the Basic and Specific Classification or the Bouhanna scales. Dermatologists should coordinate care with the patient's primary gender-affirming clinician(s) so that shared knowledge of all medications exists across the care team.

Association between PRO 160/120 prescriptions and incidence of benign prostatic hyperplasia complications in Germany: a retrospective cohort study.

The present study aims to analyze the impact of PRO 160/120 prescriptions on the incidence of urinary incontinence, polyuria (including nocturia), urinary retention, and erectile dysfunction in a real-world setting in Germany and to compare these data with data for the 5-ARIs finasteride and dutasteride, and the α1-adrenoceptor antagonists tamsulosin and tamsulosin/dutasteride fixed-dose combination. This retrospective study was based on the IQVIA Disease Analyzer database and included male patients with an initial prescription of PRO 160/120, finasteride, dutasteride, tamsulosin, or tamsulosin/dutasteride fixed-dose combination between January 2010 and September 2020. Multivariable logistic regression analyses adjusted for age, health insurance, specialty, and relevant co-diagnoses were performed to estimate the association between PRO 160/120 prescriptions and incidence of pre-defined outcomes. A total of 77,923 patients were included in the study, 3,035 of whom received PRO 160/120. PRO 160/120 was significantly associated with reduced incidence of urinary incontinence (OR: 1.48; 95% CI: 1.10-1.98) and urinary retention compared to tamsulosin (OR: 3.39; 95% CI: 1.75-6.57 and tamsulosin/dutasteride (OR: 2.81; 95% CI: 1.35-5.82). Furthermore, PRO 160/120 significantly reduced the incidence of erectile dysfunction compared to dutasteride (OR: 2.79; 95% CI: 1.49-5.25). At the same time, patients receiving PRO 160/120 showed the same incidence of the remaining complications as those taking the reference substances. In conclusion, we observed a significant association between PRO 160/120 prescription and reduced incidence of urinary incontinence and urinary retention compared to tamsulosin and tamsulosin/dutasteride, as well as reduced incidence of erectile dysfunction compared to dutasteride.

Dutasteride nanoemulsion preparation to inhibit 5-alpha-hair follicle reductase enzymes in the hair follicle; an ex vivo study.

Alopecia is a treatable disorder that usually occurs due to high levels of 5-alpha dihydrotestosterone in hair follicles. To enhance the storage capacity of hair follicles and alleviate the inherent characteristics of dutasteride, 5-alpha reductase inhibitor, a prolonged-release nanocarrier was synthesised, and its influence on rat abdomen's skin was investigated. Results showed the lower ratio of S/Co (higher ethanol concentration) increased the hydrodynamic nanocarriers' particle size due to thermodynamic disturbance and Ostwald ripening. In contrast, an increase in surfactant through a decrease in interfacial tension resulted in smaller nanocarriers of 32.4 nm. Moreover, an increase in viscosity had an inverse correlation with the nanoemulsions' particle size. Nanocarriers containing ethanol showed less entrapment efficacy, perhaps due to the rapid dissolution of dutasteride into ethanol during nanoemulsification, while, based on Stokes' equation, the addition of ethanol resulted in smaller particle size and stability of the system. Skin permeation analysis using Franz diffusion cells showed nanocarriers could pass through the skin and release dutasteride for 6 days. In conclusion, the optimum concentration of ingredients is decisive in guaranteeing the ideal particle size, stability, and skin permeation of nanocarriers. The Present dutasteride nanocarrier would promise a prolonged and sustained-release drug delivery system for Alopecia therapy.

5α-reductase inhibitors and the risk of bladder cancer in a large, population-based cohort.

PURPOSE: The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. Our objective was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality. PATIENTS AND METHODS: We used routinely collected health care data from Ontario, Canada. Men ≥66 years of age with a prescription for a 5ARI were matched to non-5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We measured 5 additional baseline variables which may have impacted the risk of future BC diagnosis: prior cystoscopy, urine cytology, urinalysis, gross hematuria episodes, and transurethral resection of a bladder lesion. Only the first period of continuous usage of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy and ended at the last date of 5ARI exposure + 1 year. RESULTS: We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride) between 2003 and 2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (interquartile range 1.00, 4.27). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.82-1.32) during the period of 0 to <2 years of 5ARI use; however, after ≥2 years of 5ARI use, the risk of BC diagnosis was significantly lower among the 5ARI group (HR 0.82, 95% CI 0.79-0.94). In a similarly adjusted model, BC mortality was lower among 5ARI users, but no longer statistically significant (HR 0.82, 95% CI 0.65, 1.02). When stratified by type of 5ARI, finasteride significantly reduced the risk of BC diagnosis after ≥2 years of continuous use (HR 0.86, 95% CI 0.76, 0.96); however, dutasteride did not (HR 0.92, 95% CI 0.83, 1.03). CONCLUSIONS: In a large cohort of men, the use of a 5ARI was associated with a significantly decreased the risk of BC diagnosis after more than 2 years of continuous therapy.