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1.
Fr J Urol ; 34(2): 102574, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38717461

ABSTRACT

INTRODUCTION: Treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) has shifted over the last decades, with medical therapy becoming the primary treatment modality while surgery is being reserved mostly to patients who are not responding to medical treatment or presenting with complications from BPH. Here, we aim to to discuss the optimal timing of surgical management of LUTS/BPH. MATERIALS AND METHODS: A literature search was conducted on Pub-Med/MEDLINE database to identify reports published from January 1990 until January 2022 by combining the following MeSH terms: "Lower Urinary Tract Symptoms"; "Prostatic Hyperplasia"; "Prostatic Hyperplasia/therapy"; "Prostatic Hyperplasia/complications"; "Treatment Outcome"; "Time-to-Treatment". Evidence supporting or not early surgical treatment of BPH was examined and reported in a pros and cons form. RESULTS: The "pro early surgery" highlighted the superior efficacy and cost-effectiveness of surgery over medical treatment for BPH, as well as the possibility of worse postoperative outcomes for delayed surgical treatment. The "con early surgery" considered that medical therapy is efficient in well-selected patients and can avoid the serious risks inherent to surgical treatment of BPH including important sexual side effects. CONCLUSIONS: Clinical trials comparing the outcomes for prolonged medical therapy versus early surgical treatment could determine which approach is more beneficial in the long-term in context of the aging population. Until then, both approaches have their advantages and patients should be involved in the treatment decision.


Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Time-to-Treatment , Prostatic Hyperplasia/surgery , Humans , Male , Lower Urinary Tract Symptoms/surgery , Lower Urinary Tract Symptoms/etiology , Prostatectomy/methods , Prostatectomy/adverse effects , Time Factors
2.
Int. braz. j. urol ; 50(2): 119-135, Mar.-Apr. 2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1558056

ABSTRACT

ABSTRACT Purpose: Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones. Materials and Methods: Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool. Results: There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001). In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal. Conclusion: Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.

3.
Curr Urol Rep ; 25(5): 93-98, 2024 May.
Article in English | MEDLINE | ID: mdl-38448685

ABSTRACT

PURPOSE OF REVIEW: This review aims to identify and summarize the current literature on the most recent therapeutic agents and combination strategies for the medical management of lower urinary tract symptoms resulting from benign prostatic hyperplasia. RECENT FINDINGS: The latest advancements in BPH therapy have been in combination strategies. Alpha blockers continue to be the mainstay of treatment, but research is exploring the synergistic benefits of combining them with 5-alpha reductase inhibitors (5-ARIs), phosphodiesterase-5 (PDE5) inhibitors, and beta-3 agonists. The alpha-blocker + 5-ARI combination remains ideal for enlarged, significantly reducing clinical progression risk compared to monotherapy. Alpha-blocker + PDE5 inhibitor combinations appear safe and potentially beneficial for men with concomitant erectile dysfunction; sildenafil might hold an edge over tadalafil based on limited data. Beta-3 agonists show synergistic effects with alpha blockers for residual storage symptoms, offering similar efficacy to anticholinergics but with a better side effect profile.


Subject(s)
Erectile Dysfunction , Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Male , Humans , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/drug therapy , Drug Therapy, Combination , Erectile Dysfunction/drug therapy , Phosphodiesterase 5 Inhibitors/therapeutic use , Tadalafil/therapeutic use , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/complications , Adrenergic alpha-Antagonists/therapeutic use , Treatment Outcome
4.
Biomolecules ; 14(2)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38397430

ABSTRACT

Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure (p 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively (p 0.596). IPCa was detected in 37.6 and 62.5%, respectively (p 0.089). The tumor GG distribution based on 5-ARI exposure was similar (p 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.


Subject(s)
Cyanoacrylates , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/pathology , Prostate/pathology , Magnetic Resonance Imaging/methods , 5-alpha Reductase Inhibitors
5.
Int Braz J Urol ; 50(2): 119-135, 2024.
Article in English | MEDLINE | ID: mdl-38386784

ABSTRACT

PURPOSE: Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones. MATERIALS AND METHODS: Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool. RESULTS: There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001).In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal. CONCLUSION: Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Testosterone , Humans , Male , Databases, Factual , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypercholesterolemia , Reference Values , Testosterone/metabolism
6.
World J Mens Health ; 42(2): 460-466, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38164032

ABSTRACT

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

7.
Actas Urol Esp (Engl Ed) ; 48(2): 150-154, 2024 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-37604401

ABSTRACT

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


Subject(s)
Laser Therapy , Lasers, Solid-State , Prostatic Hyperplasia , Male , Humans , 5-alpha Reductase Inhibitors , Prostate , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/complications , Retrospective Studies , Lasers, Solid-State/therapeutic use , Postoperative Complications/surgery , Hemoglobins
8.
Prostate ; 84(4): 403-413, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38149792

ABSTRACT

BACKGROUND: It is uncertain how long combination therapy should be continued in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). We investigated the withdrawal effects of α1-adrenergic receptor blocker (AB) or 5α-reductase inhibitor (5ARI) following successful combination therapy. METHODS: This prospective, randomized, open-label, parallel trial enrolled 222 patients with BPH/LUTS who showed at least a seven-point improvement in International Prostate Symptom Score-total (IPSS-T) and a ≥ 20% reduction in prostate volume (PV) following the initiation of combination therapy. Patients were randomized in a 1:1:1 ratio into continued-combination, AB-withdrawal, and 5ARI-withdrawal groups. IPSS, overactive bladder symptom score, EuroQol-five-dimensional questionnaire (EQ-5D-5L), EuroQol-visual analog scale (EQ-VAS), prostate volume (PV), maximal flow rate, postvoid residual urine (PVR), and prostate-specific antigen level were assessed every 6 months for 24 months. The predictors of IPSS-T deterioration were evaluated. RESULTS: At Month 24, IPSS-T deterioration (≥2 point) was observed in 20/72 (27.8%) and 19/72 (26.4%) patients in the AB- and 5ARI-withdrawal groups, respectively. Among them, 4/72 (5.6%) and 4/70 (5.7%) patients required readdition of the withdrawn drug (p = 0.868). In the continued combination group, EQ-VAS improved at Month 24 compared to baseline (p = 0.028). At Month 24, the AB-withdrawal group showed improvements in EQ-5D-5L, EQ-VAS, and PVR (all p < 0.005), while the 5ARI-withdrawal group showed improvement in IPSS-S (p = 0.011). Diabetes mellitus was associated with IPSS-T deterioration at Month 24 (p = 0.020). CONCLUSIONS: In patients with BPH/LUTS who are reluctant to continue combination therapy, AB or 5ARI withdrawal may be offered in men with improvement in IPSS-T by at least seven points and reduction in PV by at least 20%.


Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Urinary Retention , Male , Humans , Prostatic Hyperplasia/drug therapy , Prospective Studies , Drug Therapy, Combination , 5-alpha Reductase Inhibitors/therapeutic use , Adrenergic alpha-Antagonists/therapeutic use , Lower Urinary Tract Symptoms/etiology , Urinary Retention/etiology , Oxidoreductases/therapeutic use , Treatment Outcome
9.
World J Urol ; 41(11): 2967-2974, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37787941

ABSTRACT

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Male , Humans , Aged , Cohort Studies , 5-alpha Reductase Inhibitors/therapeutic use , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/drug therapy , Magnetic Resonance Imaging/methods , Oxidoreductases , Image-Guided Biopsy/methods
10.
Dermatol Ther (Heidelb) ; 13(8): 1721-1731, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37432644

ABSTRACT

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

11.
Lancet Reg Health Eur ; 31: 100672, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37415648

ABSTRACT

Background: Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms improvement after PAE and medical treatment. Methods: A randomised, open-label, superiority trial was set in 10 French hospitals. Patients with bothersome lower urinary tract symptoms (LUTS) defined by International Prostatic Symptom Score (IPSS) > 11 and quality of life (QoL) > 3, and BPH ≥50 ml resistant to alpha-blocker monotherapy were randomly assigned (1:1) to PAE or Combined Therapy ([CT], oral dutasteride 0.5 mg/tamsulosin hydrochloride 0.4 mg per day). Randomisation was stratified by centre, IPSS and prostate volume with a minimisation procedure. The primary outcome was the 9-month IPSS change. Primary and safety analysis were done according to the intention-to-treat (ITT) principle among patients with an evaluable primary outcome. ClinicalTrials.gov Identifier: NCT02869971. Findings: Ninety patients were randomised from September 2016 to February 2020, and 44 and 43 patients assessed for primary endpoint in PAE and CT groups, respectively. The 9-month change of IPSS was -10.0 (95% confidence interval [CI]: -11.8 to -8.3) and -5.7 (95% CI: -7.5 to -3.8) in the PAE and CT groups, respectively. This reduction was significantly greater in the PAE group than in the CT group (-4.4 [95% CI: -6.9 to -1.9], p = 0.0008). The IIEF-15 score change was 8.2 (95% CI: 2.9-13.5) and -2.8 (95% CI: -8.4 to 2.8) in the PAE and CT groups, respectively. No treatment-related AE or hospitalisation was noticed. After 9 months, 5 and 18 patients had invasive prostate re-treatment in the PAE and CT group, respectively. Interpretation: In patients with BPH ≥50 ml and bothersome LUTS resistant to alpha-blocker monotherapy, PAE provides more urinary and sexual symptoms benefit than CT up to 24 months. Funding: French Ministry of Health and a complementary grant from Merit Medical.

12.
Acta Oncol ; 62(5): 438-443, 2023 May.
Article in English | MEDLINE | ID: mdl-37216488

ABSTRACT

BACKGROUND: We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. METHODS: This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. RESULTS: Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). CONCLUSION: This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Stomach Neoplasms , Male , Humans , Cohort Studies , 5-alpha Reductase Inhibitors/therapeutic use , Stomach Neoplasms/drug therapy , Sweden/epidemiology , Esophageal Neoplasms/drug therapy , Adenocarcinoma/pathology , Oxidoreductases
13.
Transl Androl Urol ; 12(3): 487-496, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37032761

ABSTRACT

5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology and mechanisms of action for 5-ARIs and how this relates to multiple clinical indications. Of note, is the debunked association between finasteride and increased risk of high-grade prostate cancer. Furthermore, adverse effects of 5-ARI use are detailed in this review, with specific mentions to post-finasteride syndrome. In addition to overviews pertaining to BPH and prostate cancer, much attention has also been focused on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The androgen axis may be associated with an increased virulence for SARS-CoV-2 in men, with some reporting a correlation between the severity of illness and androgenic alopecia. Since these observations, the role of antiandrogens, including 5-ARIs, has been explored further in SARS-CoV-2. Increasing understanding of pathological processes involving the androgen axis in which 5-ARIs work, has led to increasing clinical indications for 5-ARIs. Several novel off-label indications have been suggested including its potential role in the pathogenesis of SARS-CoV-2, but to date, these claims have not been substantiated. Previously held truths regarding the role of 5-ARIs and prostate carcinogenesis have been contested, inadvertently leading to the re-exploration of 5-ARIs utility in prostate cancer. With growing evidence into pathological processes involving the androgen axis, 5-ARIs are likely to become increasingly more used. This review serves as a timely update of 5 ARIs pharmacology, current indications and potential future directions.

14.
Prostate ; 83(10): 980-989, 2023 07.
Article in English | MEDLINE | ID: mdl-37057816

ABSTRACT

OBJECTIVES: To assess the risk of benign prostatic hyperplasia (BPH)-related surgery and acute urinary retention (AUR) in men treated with 5-alpha-reductase inhibitor (5-ARI) versus alpha-blocker monotherapy in routine clinical care over 15 years of follow-up. METHODS: Using population-based Danish Health registries, we identified all new-users of 5-ARI or alpha-blocker monotherapy in Denmark, 1997-2017. We defined an index date 180 days after the date of first prescription and included men who redeemed at least one additional prescription before the index date. We used multiple imputation to replace missing prostate-specific antigen values. We performed propensity score-weighted Cox regression to estimate weighted hazard ratios (wHRs) and cumulative incidence function to estimate weighted cumulative risks of BPH-related surgery and AUR in intention to treat (ITT) and per protocol (PP) analyses. RESULTS: We included 18,421 and 95,984 men treated with 5-ARI and alpha-blocker monotherapy, respectively. Overall, treatment with 5-ARI monotherapy was associated with a reduced risk of BPH-related surgery (ITT wHR = 0.73 (95% confidence interval [CI]: 0.68-0.78), PP wHR = 0.77 (95% CI: 0.70-0.84) and AUR (ITT wHR = 0.73 (95% CI: 0.67-0.78), PP wHR = 0.75 (95% CI: 0.66-0.84). The 15-year risk of BPH-related surgery in men treated with 5-ARI versus alpha-blocker monotherapy was 14.8% (95% CI: 14.1%-15.5%) versus 19.1% (95% CI: 18.7%-19.5%) in the ITT analysis and 13.8% (95% CI: 12.6%-14.9%) versus 17.5% (95% CI: 16.9%-18.0%) in the PP analysis. The 15-year risk of AUR in men treated with 5-ARI versus alpha-blocker was 13.0% (95% CI: 12.3%-13.6%) versus 16.6% (95% CI: 16.3%-17.0%) in the ITT analysis and 12.6% (95%: 11.3%-14.0%) versus 16.9% (95% CI: 16.3%-17.6%) in the PP analysis. CONCLUSION: Treatment with 5-ARI versus alpha-blocker monotherapy in routine clinical care was associated with a reduced risk of BPH-related surgery and AUR for up to 15 years of follow-up. After 15 years of follow-up, the relative risk reduction was 21%-25% and the absolute risk reduction was 4%.


Subject(s)
Prostatic Hyperplasia , Urinary Retention , Male , Humans , 5-alpha Reductase Inhibitors/adverse effects , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/complications , Urinary Retention/epidemiology , Urinary Retention/etiology , Adrenergic alpha-Antagonists/adverse effects , Drug Therapy, Combination
15.
Clin Genitourin Cancer ; 21(2): 314.e1-314.e7, 2023 04.
Article in English | MEDLINE | ID: mdl-36402643

ABSTRACT

INTRODUCTION: Androgen suppression therapy has been associated with a lower incidence of bladder cancer (BCa) or improved overall/cancer-specific survival. Results are ofent conflicting; therefore, we aim to assess the impact of use of finasteride on overall survival (OS) for BCa using multi-institutional database. METHODS: The South Texas Veterans Healthcare System from 5 medical centers was queried for patients with BCa with or without use of finasteride after diagnosis of BCa. The primary outcome was the impact of finasteride use after diagnosis on the OS in BCa and in the high-risk Non-muscle invasive BCa (NMIBC) cohort. RESULTS: A total of 1890 patients were included, amongst which 619 (32.8%) men were classified as finasteride users and 1271 (67.2%) men as controls. At a median (IQR) follow up of 53.8 (27.4, 90.9) months, death due to any cause was noted in 272 (43.9%) finasteride-treated, and 672 (49.3%) control groups (P = .028). The patients in the finasteride group had significantly better OS in overall cohort (112.1 months vs. 84.8 months, P < .001) as well as in the NMIBC cohort (129.3months vs. 103.2 months, P = .0046). The use of finasteride was independently associated with improved OS in both, overall cohort (HR 0.74, 95% CI 0.63-0.86; P < .001) and in the NMIBC cohort (HR = 0.71, 95% CI 0.55-0.93; P = .011). CONCLUSION: Finasteride use is associated with the improved overall survival in patients with BCa, specifically in patients with NMIBC. We, further, propose a randomized clinical trial to investigate the use of finasteride in BCa patients.


Subject(s)
Finasteride , Urinary Bladder Neoplasms , Male , Humans , Female , Finasteride/therapeutic use , Retrospective Studies
16.
Prostate Int ; 10(4): 213-217, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36570649

ABSTRACT

Objective: To evaluate the short-term efficacy of Dutasteride in the management of chronic prostatitis (CP)/chronic pelvic pain syndrome. Materials and methods: A randomized placebo-controlled double-blind study was conducted that including 50 patients diagnosed with CP based on the presence of pelvic pain for ≥3 months of the preceding 6 months. Patients were randomized into 2 equal groups to evaluate Dutasteride of 0.5 mg once daily that was given for 3 months compared to a placebo. Results: Forty-nine patients were evaluated after the follow-up period with no statistically significant difference in the perioperative demographic data. The mean age of the Dutasteride group was 48.3 (range 41-62) compared to a mean age of 46.5 (range 44-60) in the placebo group. There was a highly statistically significant improvement in the Dutasteride group compared to its preoperative parameters and the placebo compared group in the terms of pain, urinary scores, and total National Institutes of Health CP symptom score. Moderate and marked improvement in patients' symptomatology was seen in 56% of the dutasteride group, while only 8% in the dutasteride group failed to show an improvement with no significant side effects noted in our study. Conclusion: The short-term outcome of dutasteride therapy showed an improvement in the National Institutes of Health-CP symptom score compared to a placebo in the treatment of category IIIB CP. The trial was registered in the clinical trialgov registry with a registration number: NCT04756206.

17.
Int. braz. j. urol ; 48(4): 688-695, July-Aug. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1385145

ABSTRACT

ABSTRACT Purpose Patients often take 5-alpha reductase inhibitors (5-ARIs) for the management of benign prostatic hyperplasia. However, 5-ARIs can decrease prostate specific antigen (PSA) by approximately half and therefore may lead to false negative PSA tests. We investigated false-screening rates in men on 5-ARIs undergoing PSA testing and whether ordering physicians noticed false negative findings. Materials and Methods A single institution, retrospective study was conducted on patients with a PSA value documented between 2014 and 2017. Patient demographics, PSA results, 5-ARI usage, and providing clinician characteristics were collected. Published normal PSA values were used to determine PSA test positivity; values for those on 5-ARIs were doubled. Results A total of 29,131 men were included. 1,654 (5.7%) were prescribed 5-ARIs at least 12 months prior to PSA evaluation. 118 men (7.1%) had a value that would be positive if corrected for 5-ARI usage, 33 (27.9%) of which had no indication that the provider had noted this. There was no effect on rates of false negative values if the PSA was ordered by a different provider than the one who prescribed the 5-ARI (p = 0.837). However, if the provider who ordered the PSA test was an urologist, the likelihood that a false negative value would be identified was lower (p=0.001). Conclusions More than a quarter of men with false negative tests were missed. This occurred more often when the ordering provider was not an urologist. An educational opportunity exists to improve the quality of PSA testing by preventing false negative tests.

18.
J Clin Med ; 11(13)2022 Jun 22.
Article in English | MEDLINE | ID: mdl-35806900

ABSTRACT

The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability.

19.
Int Braz J Urol ; 48(4): 688-695, 2022.
Article in English | MEDLINE | ID: mdl-35594325

ABSTRACT

PURPOSE: Patients often take 5-alpha reductase inhibitors (5-ARIs) for the management of benign prostatic hyperplasia. However, 5-ARIs can decrease prostate specific antigen (PSA) by approximately half and therefore may lead to false negative PSA tests. We investigated false-screening rates in men on 5-ARIs undergoing PSA testing and whether ordering physicians noticed false negative findings. MATERIALS AND METHODS: A single institution, retrospective study was conducted on patients with a PSA value documented between 2014 and 2017. Patient demographics, PSA results, 5-ARI usage, and providing clinician characteristics were collected. Published normal PSA values were used to determine PSA test positivity; values for those on 5-ARIs were doubled. RESULTS: A total of 29,131 men were included. 1,654 (5.7%) were prescribed 5-ARIs at least 12 months prior to PSA evaluation. 118 men (7.1%) had a value that would be positive if corrected for 5-ARI usage, 33 (27.9%) of which had no indication that the provider had noted this. There was no effect on rates of false negative values if the PSA was ordered by a different provider than the one who prescribed the 5-ARI (p = 0.837). However, if the provider who ordered the PSA test was an urologist, the likelihood that a false negative value would be identified was lower (p=0.001). CONCLUSIONS: More than a quarter of men with false negative tests were missed. This occurred more often when the ordering provider was not an urologist. An educational opportunity exists to improve the quality of PSA testing by preventing false negative tests.


Subject(s)
Prostate-Specific Antigen , Prostatic Hyperplasia , Prostatic Neoplasms , 5-alpha Reductase Inhibitors/therapeutic use , False Negative Reactions , Humans , Male , Prostate-Specific Antigen/blood , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/drug therapy , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/prevention & control , Retrospective Studies
20.
J Urol ; 207(4): 876-884, 2022 04.
Article in English | MEDLINE | ID: mdl-34854747

ABSTRACT

PURPOSE: As men age, the prostate continues to grow on average 2.5% per year. While the variable growth rate of the total prostate gland is recognized, the growth rate of different prostate zones remains largely unclear. We evaluated the growth patterns of the prostate zones and identified clinical parameters contributing to the zonal growth rates. MATERIALS AND METHODS: Prostate magnetic resonance imaging (MRI) data and clinical information were obtained retrospectively on 156 patients who had at least 3 prostate MRIs between 2003 and 2018. Different prostate zonal volumes were measured and analyzed. The outcome was analyzed using linear regression. RESULTS: We observed that prostate growth rates vary depending on body mass index (BMI), transition zone index (TZI), the prostate zone and 5-alpha reductase inhibitor (5ARI) use. The peripheral zone volume growth rates increased with age and peaked at 60-70 years of age (p=0.047), while the transition zone volume demonstrates continuous growth without a peak through all ages. BMI and TZI are associated with the growth rate of the peripheral zone (p=0.026, p <0.001, respectively) but not the transition zone growth rate. 5ARI use is significantly associated with the reduction in the transition zone growth rate (p=0.033), not the peripheral zone. In addition, patients with TZI greater than 60% had the most significant reduction in the transition zone growth rate while taking 5ARI (p <0.001). CONCLUSIONS: Transition and peripheral zones of the prostate grow at variable rates. BMI and TZI affect peripheral zone growth rate, while 5ARI use reduces the transition zone growth rate.


Subject(s)
Aging/physiology , Body Mass Index , Prostate/growth & development , Prostatic Hyperplasia/drug therapy , 5-alpha Reductase Inhibitors/therapeutic use , Aged , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Organ Size , Prostate/diagnostic imaging , Prostate/drug effects , Prostatic Hyperplasia/pathology , Retrospective Studies
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