5-ARI Use Research Articles

Consensus Report on Controversial Use of 5-Alpha-Reductase Inhibitor in Patients with Benign Prostatic Hyperplasia under Taiwan National Health Insurance Regulations

Introduction: Although the National Health Insurance regulations for 5-alpha-reductase inhibitor (5ARI) use is well documented, urologists and medical claims review committee members have sometimes felt confused when determining claims for 5ARI use in certain circumstances. Thus, a consensus meeting was held to discuss how to use 5ARI appropriately in such circumstances. Materials and Methods: The expert urologists and medical claim review committee members reviewed seven controversial cases with related clinical evidence and voted for approval of the use of 5ARI after vigorous discussion. Results: Among the seven cases, a consensus was achieved in four. First, transrectal ultrasound of the prostate was not necessary if the patient already had other images. Second, prescribing 5ARI was affirmed in patients who had high prostate-specific antigen but who refused biopsy. Third, the normal prostate-specific antigen range was based on the 2003 version of the consensus of prostatic cancer of the National Health Research Institutes. Four, 5ARI could be prescribed in patients with improved clinical data but who were unable to meet the other regulatory criteria. Finally, of the three remaining cases, one case was denied, and in two cases, half of the members approved, and half rejected the claim for 5ARI use. Conclusion: This consensus report provided clarification for Taiwanese urologists and medical claims review committee members on reimbursable use of 5ARI in controversial cases.

Algorithmic approach to the treatment of frontal fibrosing alopecia: A systematic review

To the Editor: Frontal fibrosing alopecia (FFA) is a lymphocytic primary cicatricial alopecia initially described by Kossard in 1994.1Vañó-Galván S. Molina-Ruiz A.M. Serrano-Falcón C. et al.Frontal fibrosing alopecia: a multicenter review of 355 patients.J Am Acad Dermatol. 2014; 70: 670-678Abstract Full Text Full Text PDF PubMed Scopus (277) Google Scholar FFA most commonly affects postmenopausal women, although cases in premenopausal women and men have been described. FFA is characterized by frontotemporal hairline recession, eyebrow hair loss, and perifollicular erythema and hyperkeratosis. There is no consensus for the treatment of FFA, and current therapy is aimed at preventing the progression of hair loss. Although some consider FFA to be a variant of lichen planopilaris, there might be treatment considerations unique to FFA. The authors have conducted a systematic review of the current literature to help in the development of a treatment algorithm for patients with FFA. On January 17, 2018, we conducted a search of the PubMed database using the term “frontal fibrosing alopecia treatment.” Publications not in English and those not including specific treatment outcomes were eliminated. A total of 22 studies were included in our review and are summarized in Supplementary Table I, available via Mendeley at https://doi.org/10.17632/nkt4k79spw.1. We utilized the levels of evidence tool from the Oxford Centre for Evidence-Based Medicine to assign grades of recommendation to each study. Treatment response was most often described as disease improvement, stabilization, or progression by authors of the original articles. Treatment regimens for 816 patients were described in the 22 studies. Topical and intralesional corticosteroids are often first-line therapies due to their minimal side effect profile and were most often used in the reviewed studies. These therapies were rarely used as solitary treatments, making it difficult to gauge their efficacy. In our review, hydroxychloroquine and 5a-reductase inhibitor (5aRIs; dutasteride and finasteride) were the most effective therapies. Sixty of 83 (72%) patients treated with hydroxychloroquine and 207 of 297 (70%) patients treated with 5aRIs experienced disease stabilization and improvement. The endpoint for most studies was disease stabilization, and in this regard, hydroxychloroquine and 5aRIs performed similarly. Patients typically experienced results within 6-12 months, although some continued to see improvement up to 2 years after treatment. Systemic corticosteroids were rarely used and were limited to cases of severe inflammation. Other therapies were utilized much less frequently with variable outcomes (Supplementary Table I). Despite decreased androgen levels noted in FFA patients, 5aRIs might nevertheless be an effective treatment option for these patients.2Ranasinghe G.C. Piliang M.P. Bergfeld W.F. Prevalence of hormonal and endocrine dysfunction in patients with lichen planopilaris (LPP): a retrospective data analysis of 168 patients.J Am Acad Dermatol. 2017; 76: 314-320Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Use of 5aRIs should be limited to patients who are postmenopausal or on reliable contraception.3Donovan J.C. Finasteride-mediated hair regrowth and reversal of atrophy in a patient with frontal fibrosing alopecia.JAAD Case Rep. 2015; 1: 353-355Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Given the findings of this review, we suggest the treatment approach for FFA outlined in Fig 1. In patients with continued disease progression despite standardized therapies, special consideration should be given to emerging therapies, such as platelet-rich plasma and low-level light-emitting diodes.4Fonda-Pascual P. Moreno-Arrones O.M. Saceda-Corralo D. et al.Effectiveness of low-level laser therapy in lichen planopilaris.J Am Acad Dermatol. 2018; 78: 1020-1023Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 5Dina Y. Aguh C. Use of platelet-rich plasma in cicatricial alopecia.Dermatol Surg. 2018; : 1https://doi.org/10.1097/DSS.0000000000001635Crossref PubMed Scopus (13) Google Scholar Limitations of this study include varying doses and lengths of treatments and subjective interpretation of disease progression and stabilization. Because there is currently no global index scale for FFA, it is difficult to assess the true efficacy of treatment. In addition, in some instances it was unclear whether resolution was due to the natural history of the disease or employment of a specific therapy.1Vañó-Galván S. Molina-Ruiz A.M. Serrano-Falcón C. et al.Frontal fibrosing alopecia: a multicenter review of 355 patients.J Am Acad Dermatol. 2014; 70: 670-678Abstract Full Text Full Text PDF PubMed Scopus (277) Google Scholar Moving forward, randomized controlled trials are necessary to evaluate the effectiveness of various treatments of FFA.

Impact of 5α-reductase inhibitor and α-blocker therapy for benign prostatic hyperplasia on prostate cancer incidence and mortality.

To investigate the use of 5α-reductase inhibitors (5ARIs) and α-blockers among men with benign prostatic hyperplasia (BPH) in relation to prostate cancer (PCa) incidence, severity and mortality. A retrospective 20-year cohort study in men residing in Saskatchewan, aged 40-89 years, with a BPH-coded medical claim between 1995 and 2014, was conducted. Cox proportional hazards regression was used to compare incidence of PCa diagnosis, metastatic PCa, Gleason score 8-10 PCa, and PCa mortality among 5ARI users (n = 4 571), α-blocker users (n = 7 764) and non-users (n = 11 677). In comparison with both non-users and α-blocker users, 5ARI users had a ~40% lower risk of a PCa diagnosis (11.0% and 11.4% vs 5.8%, respectively), and α-blocker users had an 11% lower risk of a PCa diagnosis compared with non-users. Overall, the incidence of metastatic PCa and PCa mortality was not significantly different among 5ARI or α-blocker users compared with non-users (adjusted hazard ratios [HR] of metastatic PCa: 1.12 and 1.13, respectively, and PCa mortality: 1.11 and 1.18, respectively, P > 0.05 for both drugs), but both 5ARI and a-blocker users had ~30% higher risk of Gleason score 8-10 cancer, adjusted HR 1.37, 95% confidence interval [CI] 1.03-1.82, P = 0.03, and adjusted HR 1.28, 95% CI 1.03-1.59, P = 0.02, respectively compared with non-users. The use of 5ARIs was associated with lower risk of PCa diagnosis, regardless of comparison group. Risk of high grade PCa was higher among both 5ARI users and α-blocker users compared with non-users; however, this did not translate into higher risk of PCa mortality.

Self-reported Black race predicts significant prostate cancer independent of clinical setting and clinical and socioeconomic risk factors

Introduction and ObjectiveStudies have linked Black race to prostate cancer (CaP) risk but most fail to account for established risk factors such as 5-ARI use, prostate volume, socioeconomic status, and hospital setting. We assess whether Black race remains associated with CaP and Gleason ≥3 + 4 CaP, after adjusting for clinical setting and socioeconomic and clinical factors at prostate biopsy, with a focus on men aged 40-54 years, who may be excluded from current screening guidelines. MethodsWe recruited 564 men age 40-79 undergoing initial prostate biopsy for abnormal PSA or digital rectal examination (DRE) from three publicly funded and two private hospitals from 2009-2014. Univariate and multivariate analyses examined the associations between hospital type, race, West African Ancestry (WAA), clinical, and sociodemographic risk factors with CaP diagnosis and Gleason ≥3 + 4 CaP. Given changes in CaP screening recommendations, we also assess the multivariate analyses for men aged 40-54. ResultsBlack and White men had similar age, BMI, and prostate volume. Black men had higher PSA (8.10 ng/mL vs. 5.63 ng/mL) and PSA density (0.22 ng/mL/cm3 vs. 0.15 ng/mL/cm3, all p < 0.001). Blacks had higher frequency of CaP (63.1% vs. 41.5%, p<0.001) and Gleason ≥3+4 CaP relative to Whites in both public (27.7% vs 11.6%, p<0.001) and private (48.4% vs 21.6%, p = 0.002) settings. In models adjusted for age, first degree family history, prostate volume, 5-ARI use, hospital type, income, marital and educational status, Black race was independently associated with overall CaP diagnosis (OR = 2.13, p = 0.002). There was a significant multiplicative interaction with Black race and abnormal DRE for Gleason ≥3 + 4 CaP (OR = 2.93, p = 0.01). WAA was not predictive of overall or significant CaP among Black men. Black race (OR = 5.66, p = 0.02) and family history (OR = 4.98, p = 0.01) were independently positively associated with overall CaP diagnosis for men aged 40 to 54. ConclusionsBlack race is independently associated with CaP and Gleason ≥3+4 CaP after accounting for clinical and socioeconomic risk factors including clinical setting and WAA, and has a higher odds ratio of CaP diagnosis in younger men. Further investigation into optimizing screening in Black men aged 40 to 54 is warranted.

Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high grade prostate cancer: a French population-based study.

To assess the association between 5α-reductase inhibitor (5-ARI) use and high grade (Gleason score 8-10) prostate cancer. We conducted a population-based nested matched case-control study using the French national health insurance database linked to data from all pathology laboratories in Brittany, France. Among 74596 patients with ≥1 drug reimbursement for symptomatic benign prostate hypertrophy (BPH) between 1 January 2010 and 31 December 2011, 767 incident prostate cancer cases between 1 January 2012 and 31 December 2013 were matched according to age and delay between the first observed delivery of drug for BPH (5-ARIs, α-blockers or phytotherapy) and diagnostic date of the case to five control patients, using an incidence density sampling design. A total of 963 patients (153 cases, 810 controls) had been exposed to 5-ARIs. A significant heterogeneity (P = 0.005) was detected across cancer grades when estimating the association between prostate cancer and long-term (≥2years) 5-ARI use vs no 5-ARI exposure: adjusted conditional odds ratio 1.76 (95% confidence interval [CI] 0.97-3.21) for Gleason score ≥8 and 0.64 (95% CI 0.44-0.93) for Gleason score < 8. Our results indicate an increased risk of high grade and a decreased risk of low grade prostate cancer associated with 5-ARI use. Patients treated for >2years with 5-ARIs should be informed about the increased risk of development of high grade disease.

Continued Five-Alpha Reductase Inhibitor Use After Prostate Cancer Diagnosis and the Risk of Reclassification and Adverse Pathological Outcomes in the Canary Prostate Active Surveillance Study (PASS)

PurposeOutcomes of patients who enroll in active surveillance (AS) programs for prostate cancer (PCa) while taking five-alpha reductase inhibitors (5-ARIs) have not been well defined. We sought to determine the association of 5-ARI use with risk of reclassification in the Canary Prostate Active Surveillance Study (PASS). Materials and MethodsParticipants in the multicenter PASS were enrolled between 2008-2016. Inclusion criteria were current or never 5-ARI user, Gleason ≤ 3+4 PCa at diagnosis, < 34% core involvement ratio at diagnosis, and ≥ 1 surveillance biopsy. 1009 men (107 5-ARI users and 902 never users) were included. Reclassification was defined as increase in Gleason score and/or increase in ratio of biopsy cores positive for cancer to ≥ 34%. Adverse pathology at prostatectomy was defined as Gleason ≥ 4+3 and/or non organ-confined disease (pT3 or N1). ResultsOn multivariable analysis, there was no difference in the risk of reclassification between 5-ARI users and never 5-ARI users (HR 0.81, p = 0.31). 5-ARI users were less likely to undergo radical prostatectomy (RP) (8% vs 18%, p=0.01) or any definitive treatment (19% vs 24%, p=0.04). Among participants who underwent RP (n=167), there was no suggestion of a difference in the rate of adverse pathology between 5-ARI users and non-users at prostatectomy. ConclusionsContinued 5-ARI use after initial diagnosis of prostate cancer was not associated with risk of reclassification on AS for men in the PASS cohort.

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

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

MP04-10 USE OF 5?-REDUCTASE INHIBITORS FOR BENIGN PROSTATIC HYPERTROPHY AND RISK OF HIGH-GRADE PROSTATE CANCER: A FRENCH POPULATION-BASED STUDY

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Epidemiology & Evaluation1 Apr 2018MP04-10 USE OF 5?-REDUCTASE INHIBITORS FOR BENIGN PROSTATIC HYPERTROPHY AND RISK OF HIGH-GRADE PROSTATE CANCER: A FRENCH POPULATION-BASED STUDY Lucie-Marie SCAILTEUX, Frédéric BALUSSON, Emmanuel NOWAK, Sébastien VINCENDEAU, Nathalie RIOUX-LECLERCQ, and Emmanuel OGER Lucie-Marie SCAILTEUXLucie-Marie SCAILTEUX More articles by this author , Frédéric BALUSSONFrédéric BALUSSON More articles by this author , Emmanuel NOWAKEmmanuel NOWAK More articles by this author , Sébastien VINCENDEAUSébastien VINCENDEAU More articles by this author , Nathalie RIOUX-LECLERCQNathalie RIOUX-LECLERCQ More articles by this author , and Emmanuel OGEREmmanuel OGER More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.160AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Association between 5-ARI use and high-grade prostate cancer is still debated since the unanticipated signal reported in PCPT and REDUCE trials. Observational studies with different designs all reported an increased risk for high grade prostate cancer, though not statistically significant. Even if somehow reassuring, those findings did not rule out an association. We then set up the CANARI study focusing on men with symptoms and complications related to benign prostatic hypertrophy. METHODS This population-based nested matched case-control study used comprehensive French Health Insurance Data (SNIIRAM) linked to data from all path labs located in Brittany, France. Among 74,596 men living in Brittany with at least one reimbursement for a drug licensed for symptomatic or complicated benign prostatic hypertrophy (5-ARI monotherapy or in association, alpha-blockers or phytotherapy) and free of prostate cancer in 2010-2011, 859 cases of incident cases (in 2012-2013) were identified and linked to pathology results; five controls per case were randomly selected using an incidence density sampling design. Conditional adjusted odds ratio (95% confidence interval) was used as a measure of association; cumulative duration exposure to 5-ARI was categorised into three classes (<1 year, 1-2 years, >= 2 years) and homogeneity across high- (Gleason score >= 8) and low-grade (Gleason score < 8) prostate cancer was investigated when comparing 5-ARI users to 5-ARI non-users.ClinicalTrials.gov identifier: NCT02873117 RESULTS 767 cases were eligible for the analysis, matched to 3835 controls; 963 men (153 cases and 810 controls) had been exposed to 5-ARI; 3 639 (614 cases and 3025 controls) were 5-ARI non-users, mostly (67%) treated by alpha-adrenoreceptor antagonists. Mean age combined was 69.3 years; men with Gleason score <8 were younger (mean age 68.2 years than men with Gleason >=8 (76.0 years). Patients exposed to 5ARI had a similar number of PSA measurement (85%) than 5ARI non-users, and a quite similar number of prostate samples (respectively 28% and 26 %). Conditional adjusted odds ratio were 0.64 (95%CI, 0.44 to 0.93) and 1.76 (95%CI, 0.97 to 3.21) for low grade and high-grade prostate cancer, respectively, when comparing 5-ARI users for at least 2 years to non users (test for heterogeneity, p = 0.0048). CONCLUSIONS Our results supported a qualitative heterogeneity when considering an association between long-term exposure to 5-ARI and prostate cancer. These results are in line with previously published randomized clinical trials and, though not yet explained, should be considered when managing long-term treatment for symptomatic benign prostatic hypertrophy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e36-e37 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Lucie-Marie SCAILTEUX More articles by this author Frédéric BALUSSON More articles by this author Emmanuel NOWAK More articles by this author Sébastien VINCENDEAU More articles by this author Nathalie RIOUX-LECLERCQ More articles by this author Emmanuel OGER More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP20-08 MR IMAGING OF PROSTATE CANCER SHOWS REDUCED ENHANCEMENT KINETIC CURVES IN MEN ON 5-ALPHA REDUCTASE INHIBITORS WITH IMPLICATIONS FOR CANCER DETECTION

You have accessJournal of UrologyImaging/Radiology: Uroradiology II1 Apr 2018MP20-08 MR IMAGING OF PROSTATE CANCER SHOWS REDUCED ENHANCEMENT KINETIC CURVES IN MEN ON 5-ALPHA REDUCTASE INHIBITORS WITH IMPLICATIONS FOR CANCER DETECTION Shivashankar Damodaran, Lori Mankowski Gettle, Kelcz Frederick, Glenn O Allen, kyle Richards, E. Jason Abel, Tracy Downs, and David Jarrard Shivashankar DamodaranShivashankar Damodaran More articles by this author , Lori Mankowski GettleLori Mankowski Gettle More articles by this author , Kelcz FrederickKelcz Frederick More articles by this author , Glenn O AllenGlenn O Allen More articles by this author , kyle Richardskyle Richards More articles by this author , E. Jason AbelE. Jason Abel More articles by this author , Tracy DownsTracy Downs More articles by this author , and David JarrardDavid Jarrard More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.678AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 5-Alpha Reductase Inhibitors (5ARI) produce duration-dependent changes in blood flow, total volume (TV) and zonal volume (ZV) of the prostate. To date, the effect of 5ARI on prostate cancer (PC) detection with MRI has not been examined. The goal of the study was to determine if 5ARI increases the conspicuity of PC on MRI, especially in the background of benign prostatic hypertrophy METHODS IRB approved retrospective study of 682 men who underwent prostate MRI. There were 217 biopsy proven cancer cases of which 13 (6%) on 5ARI were matched to 25 (12%) not on ARI based on age and Gleason Score. Two experienced GU radiologists blinded to 5ARI use reviewed the MRIs and recorded Apparent Diffusion Coefficient (ADC), maximum enhancement over baseline, and enhancement curve types of the PC and BPH nodules were measured for each patient. Statistical analysis was performed using MedCalc. RESULTS PSA (9 (4.7 -22) vs 5.6 (4.9 - 8.1); 0.09) and prostate volume (76 (47.2- 98) vs. 56 (46.7- 62.8); p=0.07) trended higher in the 5ARI groups. There were less aggressive enhancement curves in both cancer lesions (p=0.06) and benign nodules (p=0.01) in patients on 5ARI (see Table). 5ARI had no effect on ADC or maximum enhancement above baseline for either cancer or BPH nodules. ADC values did not significantly differ in malignant (p= 0.1) and benign (p=0.7) nodules in patients on 5ARI. No increased enhancement over baseline in both cancer and BPH nodules (p=0.9 and p=0.6, respectively) was noted CONCLUSIONS When patients were on 5ARI for at least three months, there was a differential blunting of enhancement kinetic curves, which was significant for BPH nodules and less marked for cancer nodules. This differential alteration of enhancement kinetic curves of BPH nodules compared to cancer nodules might be utilized enhance prostate cancer nodule detection with MRI by administering short course of 5ARI before imaging. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e255 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Shivashankar Damodaran More articles by this author Lori Mankowski Gettle More articles by this author Kelcz Frederick More articles by this author Glenn O Allen More articles by this author kyle Richards More articles by this author E. Jason Abel More articles by this author Tracy Downs More articles by this author David Jarrard More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP45-01 ANDROGENIC TO ESTROGENIC SWITCH IN THE PROSTATE GLAND OF OVERWEIGHT PATIENT

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2018MP45-01 ANDROGENIC TO ESTROGENIC SWITCH IN THE PROSTATE GLAND OF OVERWEIGHT PATIENT Zongwei Wang, Libing Hu, Shulin Wu, Shahin Tabetabaei, Chin-Lee Wu, and Aria Olumi Zongwei WangZongwei Wang More articles by this author , Libing HuLibing Hu More articles by this author , Shulin WuShulin Wu More articles by this author , Shahin TabetabaeiShahin Tabetabaei More articles by this author , Chin-Lee WuChin-Lee Wu More articles by this author , and Aria OlumiAria Olumi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1440AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The steroid 5-α reductase type 2 (SRD5A2) is critical for prostatic development and growth. Strategies to block SRD5A2 using 5-α reductase inhibitors (5ARI) remain a mainstay in the treatment of benign prostatic hyperplasia (BPH). However, one-third of men are resistant to 5ARI therapies. We previously showed that body mass index (BMI) correlates with increased SRD5A2 gene promoter methylation and decreased protein expression in men with symptomatic BPH. We have demonstrated that there is an androgenic to estrogenic switch when SRD5A2 is absent in the prostate gland. Here we wished to identify whether BMI is associated with the androgenic to estrogenic switch in human prostate tissue. METHODS Prostate specimens were collected from 35 patients who underwent transurethral resection of the prostate for symptomatic BPH at Massachusetts General Hospital. Medical records were reviewed to retrospectively collect clinical and pathological data. Patients were categorized by BMI as lean (less than 25 kg/m2), and overweight (25 kg/m2 or greater). Use and duration of α-blockers and/or 5ARIs was assessed. Methylation of SRD5A2 promoter was assessed using Methylated CpG Island Recovery Assay (MIRA). Prostatic levels of testosterone, dihydrotestosterone and estradiol were measured by HPLC-MS. RESULTS We found that BMI was significantly correlated with methylation of SRD5A2 gene promoter (p<0.05) and absence of SRD5A2 protein expression. Higher BMI was associated with higher prostatic estradiol levels (p<0.05). IIEF-5 score, International Index of Erectile Function Questionnaire score, was negatively associated with BMI (p<0.05). Treatment with 5ARIs dramatically increased the level of prostate testosterone levels and testosterone/estradiol ratio in the prostate specimens (p<0.01, p=0.01, respectively), and decreased the level of dihydrotestosterone (p<0.05). CONCLUSIONS Our study demonstrates for the first time that there is an androgenic to estrogenic switch in the prostate glands of overweight patients. Associated with body weight, somatic epigenetic silencing of SRD5A2 changes the prostatic hormonal milieu, and may modulate prostatic homeostasis and growth. Targeting the estrogenic signaling may serve as an effective treatment strategy in subset of overweight BPH patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e597 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Zongwei Wang More articles by this author Libing Hu More articles by this author Shulin Wu More articles by this author Shahin Tabetabaei More articles by this author Chin-Lee Wu More articles by this author Aria Olumi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

5-alpha-reductase inhibitor treatment for frontal fibrosing alopecia: an evidence-based treatment update.

Treatment for frontal fibrosing alopecia (FFA) is challenging, and its treatment regimen often mirrors other lymphocytic-predominant cicatricial alopecia. 5-alpha-reductase inhibitor (5ARI) has been reported with some treatment success in severe cases of FFA. To carry out evidence-based analysis of articles published on treatment efficacy and safety of 5-alpha-reductase inhibitor for the treatment of FFA. Articles published on the use of 5ARI to treat FFA between 2005 and 2017 were reviewed, analysed and graded according to the American College of Physicians outcome study grading system. There were two studies with moderate level of evidence that described the efficacy of 5ARI for the treatment of FFA. 5ARI was commonly used as adjunctive therapy with positive results in recalcitrant disease. Mild to moderate hair regrowth was reported in one grade 2 and three lower grade (one grade 3 and two grade 4) studies. There is limited evidence on the safety aspects of this medication in most studies that were analysed. Database studies might not fully account for confounders and are subjected to variations in methodology and data collection. This review demonstrated that FFA patients treated with 5ARI could achieve either disease stability or reduction in the rate of progression in selected cases. A well-designed randomized, double-blind, controlled study would strengthen the role of 5ARI as part of treatment armamentarium for FFA.

Prognostic influence of 5 alpha reductase inhibitors in patients with localized prostate cancer under active surveillance.

The incidence of prostate adenocarcinoma (PCa) is increased with the use of prostate-specific antigen (PSA). In the current study, we aimed to investigate the impact of 5- alpha- reductase inhibitors (5-ARI) on pathological progression in patients followed by active surveillance (AS). Records of 69 patients with localized prostate cancer under AS (PSA ≤15 ng/mL, PSAD ≤0.20, ≤cT2c, Gleason sum ≤3+3, the number of cancer positive cores ≤3) were evaluated retrospectively. Patients were followed-up with quarterly PSA testing and semiannual digital rectal examination during the first 2 years, and semiannual PSA testing thereafter. Repeat biopsies were done annually and whenever indicated by clinical findings. Pathological progression was defined as increasing Gleason grade, number of cancer-positive cores, and/or increasing percentage of cancer in any core. Patients using (29/69: 42%) and not using (40/69: 58%) 5-ARI were followed for a median of 39 (IQR: 23-45) and 23.5 (IQR: 17-37.5) months, respectively. Pathological progression was observed in 32% (22/69) of the patients at a median of 25 (IQR: 18-39) months. Pathological progression was observed in 34.5% (10/29) and 30% (12/40) of the patients using and not using 5-ARI, respectively (Log-rank p=0.4151). Definitive treatment was done in 31% (9/29) and 47.5% (19/40) of the patients using and not using 5-ARI, respectively. Patients who did not use 5-ARI received definitive treatment earlier than 5-ARI users (Log-rank p=0.0342). On multivariate analysis, more than 2 cancer-positive cores (HR: 11.62) and age (HR: 0.94) were independently associated with pathological progression (p<0.05), rather than 5-ARI use (p=0.148). More than 2 cancer- positive cores at the initial biopsy was the strongest covariate associated with pathological progression; these patients should not be offered AS. There was no impact of 5-ARI use on pathological progression in AS.

Clinical changes of withdrawal finasteride in patients with benign prostatic hyperplasia

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

A Focused Review on the Effects of Preoperative 5α-Reductase Inhibitors Treatment in Patients Undergoing Holmium Laser Enucleation of the Prostate: What Do We Know So Far?

The effects of medical therapy with finasteride or dutasteride during transurethral enucleation of prostate and tissue morcellation are not well defined. In theory, the risk of prostatic fibrosis versus the potential benefit of reduced intraoperative bleeding has been addressed as potential competing factors. The aim of this review was to provide evidence whether 5α-reductase inhibitors (5-ARIs) put the surgeon at a disadvantage or impact on patient outcomes. We performed a literature search of PubMed, Scopus, and Web of Science databases. All articles in English language related to the topic were reviewed to provide data on the influence of preoperative 5-ARIs in holmium laser enucleation of prostate (HoLEP). Parameters of surgical efficiency such as enucleation time and efficiency, morcellation time, operating time, prostate tissue volume resected, energy, and saline usage were evaluated in the included studies. The review failed to show any definite impact of preoperative 5-ARI use on the mentioned parameters. One study, assessing the surgical difficulty using retrospective video recording analysis, showed that use of dutasteride increases the difficulty of enucleation step, which did not translate in statistical difference of surgical efficiency in an experienced level of surgeons. Overall, 5-ARIs do not seem to affect HoLEP. However, the quality of evidence is still quite poor in comparison with other surgical techniques. Further well-designed studies are required before making any definite recommendations on the use of 5-ARIs in patients undergoing HoLEP.

5-alpha Reductase Inhibitors and risk of male breast cancer: a systematic review and meta-analysis.

Objective:To assess the relationship between 5α-reductase inhibitors (5ARIs) and the risk of male breast cancer (MBC).Material and Methods:We systematically searched Medline via PubMed, Embase and the Cochrane Library Central Register up to May 2017 to identify published articles related to 5ARIs and the risk of MBC.Results:Summary effect estimates were calculated by a random-effect model, and tests for multivariable-unadjusted pooled risk ratios (RR) and heterogeneity, as well as the sensitivity analyses were conducted to assess publication bias. All four studies were conducted in a quality assessment according to the Newcastle Ottawa Scale system. The strength of association between 5ARIs and the prevalence of MBC was evaluated by using summarized unadjusted pooled RR with a 95% confidence interval [CI]. Four studies involving 595.776 participants, mean age range from 60 to 73.2 years old, were included in a meta-analysis, which produced a summary unadjusted RR of the risk of MBC for the treatment of 5ARIs of 1.16 (95% CI 0.85-1.58, P=0.36) and the multivariable-adjusted RR is 1.03, (95% CI 0.75-1.41, p=0.86). There was no heterogeneity among included studies (I2=0%, P=0.49). Estimates of total effects were generally consistent with the sensitivity.Conclusion:We did not observe a positive association between the use of 5ARIs and MBC. The small number of breast cancer cases exposed to 5ARIs and the lack of an association in our study suggest that the development of breast cancer should not influence the prescribing of 5ARIs therapy.

Prostate cancer prevention with 5-alpha reductase inhibitors: concepts and controversies.

We review the concepts surrounding prostate cancer prevention strategies with 5-alpha reductase inhibitors (5-ARIs) and the controversies associated with their use. Updated data have shown no increased risk of death from the diagnosis of higher risk cancer; however, 5-ARIs remain controversial and not approved for prostate cancer prevention. The main theme of the review identifies the success of reducing insignificant prostate cancer and the controversy with the increased association of higher risk prostate cancer by approximately 20%. The reduction was shown to be most significant reduction in low-grade prostate cancer. The initial concern about 5-ARI use was that it could potentially increase high-risk prostate cancer leading to higher mortality in those men. Higher mortality has not been seen in follow-up data; however, 5-ARIs continue to have a black box warning and are not approved for prostate cancer prevention.

Rationale and design of the CANARI study: a case-control study investigating the association between prostate cancer and 5-alpha-reductase inhibitors for symptomatic benign prostate hypertrophy by linking SNIIRAM and pathology laboratories in a specific region in France.

Benign prostate hypertrophy (BPH) could be associated with low urinary symptoms requiring medical treatment: 5-alpha-reductase inhibitors (5-ARI) or ɑ-blockers. Two clinical trials investigating 5-ARI use in prostate cancer (PCa) primary prevention highlighted a potential safety signal with an increased risk of high-grade PCa. Later observational studies failed to show similar results but have some limits. This paper focuses on describing the protocol of the CANARI study and its feasibility, as regards the matching process of two pseudo-anonymous databases. The study concerned patients living in the Brittany region (France) between 2010 and 2013. We designed a case-control study nested within a cohort of men treated by medical drugs licensed for symptomatic BPH between 2010 and 2011. Cases were patients with incident PCa diagnosed between 2012 and 2013 identified through French Health database (SNIIRAM). Gleason score was searched through Brittany pathology laboratories. Controls were patients without PCa diagnosis. Local pathology laboratories database was constituted in Brittany, gathering Gleason scores. No unique identification number is available in France; linkage of SNIIRAM and Brittany pathology laboratories database was made by deterministic matching. We matched 859 cases to Gleason grading (119 had Gleason score ≥8 and 740 had Gleason <8); around 22% of cases received 5-ARI and 78% α-blockers or phytotherapy. The CANARI study investigated in a population of men treated for BPH the risk of PCa with 5-ARI, according to Gleason grade thanks to SNIIRAM database enriched by local pathological results.

Is There a Role for Preoperative 5 Alpha Reductase Inhibitors in Reducing Prostate Vascularity and Blood Loss?

Benign prostatic hyperplasia (BPH) and the related medical problems are a major burden as health care costs and as a cause of patient morbidity. The introduction of medical therapy largely offered an alternative to surgical therapy, and these medications have been linked with multiple positive BPH-related outcomes. With ubiquitous use, however, a variety of adverse side effects and unsupported claims to these medications have been reported both in scientific literature and popular press. The use of 5 alpha reductase inhibitors (5ARIs) to reduce recurrent bleeding due to BPH is a reasonable option for men with recurrent trips to the physician or hospital. After a largely anecdotal report of their use in the preoperative period to reduce bleeding during BPH surgery, there was interest in the use of 5ARIs for this indication considering the effusive bleeding that can occur during BPH-related surgery, a dreaded and not uncommon complication. While the pathophysiology for the use of 5ARI to reduce BPH-related bleeding is sound, the actual clinical outcomes still require scrutiny to determine if the efficacy is both scientifically valid and clinically significant. This report will review the current literature on this topic and make attempts to determine if the use of a 5ARI before BPH-related surgery should be encouraged.

Pre-radiotherapy PSA progression is anegative prognostic factor in prostate cancer patients using 5‑alpha-reductase inhibitors.

To investigate the impact of 5‑alpha-reductase inhibitor (5-ARI) use on radiotherapy outcomes for localized prostate cancer. We included 203patients on a5-ARI from our institutional database comprising over 2500patients who had been treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients received a5-ARI for urinary symptoms or active surveillance. Cancer progressions at the time of definitive treatment were analyzed according to the following criteria:(a) progression of Gleason score or increase in cancer volume on biopsy, (b)first biopsy positive for cancer after being treated for urinary symptoms with a5-ARI, and (c)prostate-specific antigen (PSA) progression with or without aprevious cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. At amedian follow-up of 38.2months (standard deviation 22.2months), 10(4.9%) patients experienced BF. Concerning prostate cancer progression criteria, 52% of men demonstrated none, 37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA progression (p= 0.004) and appearance of apositive biopsy (p< 0.001) were significant predictive factors for BF, while Gleason progression (p= 0.3) was not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA (hazard ratio, HR,5.7; 95% confidence interval, CI,1.1-28.8; p= 0.04) and the number of cancer progression factors (HR2.9, 95%CI1.2-7.0, p= 0.02) remained adverse risk factors. PSA progression experienced during 5‑ARI treatment before radiotherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

The risk of dementia with the use of 5 alpha reductase inhibitors

IntroductionThere has been considerable interest in the interplay between testosterone and cognition. Dihydrotestosterone (DHT), which has been correlated with cognitive function, is significantly reduced with the use of 5 alpha reductase inhibitors (5ARI) for prostatic enlargement. Our objective was to assess whether the use of 5ARIs was associated with an increased risk of incident dementia. MethodsWe used a matched cohort design and linked administrative data from the province of Ontario, Canada. A total of 99 covariates were measured, and a propensity score was used for matching; 81,162 men who used a 5ARIs were matched to an equal number of men who did not. ResultsNew initiation of 5ARI medication was associated with an increased risk of dementia during the first (HR 2.18, 95% CI 2.01–2.35) and second (HR 1.52, 95% CI 1.39–1.67) year, however this risk was nonsignificant among the men with the longest exposure to 5ARIs (HR 1.06, 95% CI 0.98–1.14). There was no difference in the results between types of 5ARIs. ConclusionAs the strength of the association decreased with increased exposure, the higher risk seen in the initial two years likely represents the presentation and treatment of urinary symptoms which coexist with mild cognitive impairment and eventually progresses to a diagnosis of dementia.