Search

Background: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking., Aims: To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride)., Methods: Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment., Results: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events., Conclusion: Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: Androgenetic alopecia (AGA) is the most prevalent cause of male hair loss, often requiring medical and/or surgical intervention. The US FDA has approved topical minoxidil and oral finasteride for male AGA treatment. However, some AGA patients fail to respond satisfactorily to these FDA-approved treatments and/or may experience side effects, based on their individual profiles. To mitigate the shortcomings of these treatments, researchers are now exploring alternative treatments such as newer 5-α reductase inhibitors (5-ARIs) and androgen receptor antagonists (ARAs)., Areas Covered: This article reviews the safety and effectiveness of well-known 5-α reductase inhibitors (5-ARIs) like finasteride and dutasteride, as well as the newer 5-ARIs, emerging androgen receptor antagonists (ARAs), and natural products such as saw palmetto and pumpkin seed oil in the treatment of male AGA., Expert Opinion: Although several newer 5-ARIs, ARAs, and natural products have exhibited promise in clinical trials, additional research is essential to confirm their safety and efficacy in treating male AGA. Until additional evidence is available for these agents, the preferred treatment choices for male AGA are the FDA-approved treatments, topical minoxidil, and oral finasteride.

Purpose: To study the effects of benign prostatic hyperplasia treatments, namely: alpha-adrenergic receptor blockers, 5-alpha-reductase inhibitors and phosphodiesterase-5 inhibitors on the risk of Parkinson's disease, Alzheimer's disease and mortality., Materials and Methods: All male Medicare enrollees aged 65 or above who were diagnosed with benign prostatic hyperplasia and received one of the study drugs between 2007-2020 were followed-up for the three outcomes. We used Cox regression analysis to assess the relative risk of each of the outcomes for each study drug compared to the most prescribed drug, tamsulosin, while controlling for demographic, socioeconomic and comorbidity factors., Results and Conclusions: The study analyzed 1.1 million patients for a mean follow-up period of 3.1 years from being prescribed one of the study drugs. For all outcomes, patients on tamsulosin were used as the reference for comparison. For mortality, alfuzosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.68-0.78), and doxazosin with 6% risk reduction (HR 0.94, 95%CI 0.91-0.97). For Parkinson's disease, terazosin was associated with 26% risk reduction (HR 0.74, 95%CI 0.66-0.83), and doxazosin with 21% risk reduction (HR 0.79, 95%CI 0.72-0.88). For Alzheimer's disease, terazosin was associated with 27% risk reduction (HR 0.73, 95%CI 0.65-0.82), and doxazosin with 16% risk reduction (HR 0.84, 95%CI 0.76-0.92). Tadalafil was associated with risk reduction (27-40%) in all 3 outcomes. More research is needed to elucidate the underlying mechanisms of these observations. Given the availability of safer alternatives for treating benign prostatic hyperplasia, caution should be exercised when using tamsulosin in elderly patients, especially those with an increased risk of developing neurodegenerative diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Finasteride is commonly prescribed for androgenic alopecia and benign prostatic hyperplasia. However, concerns regarding its safety have been growing as cases of cognitive dysfunction have been reported., Methods: A disproportionality analysis was conducted on data collected between 1967 and 2022 to explore the potential association. Cases of cognitive dysfunction associated with finasteride use were identified, and the reporting odds ratio (rOR) was calculated with 95% confidence intervals to determine the strength of the association between the two variables. Sensitivity analyses were conducted to account for confounding by indication., Results: Among the 54,766 cases of adverse events reported for finasteride use, 1,624 (2.97%) were associated with cognitive dysfunction. The study found a significant disproportionality for cognitive dysfunction related to finasteride use (rOR 5.43, 95% CI 5.17-5.71). Most cases were considered serious (65.83%), with no signs of recovery (58.37%). Sensitivity analyses showed that patients younger than 45 years (rOR 7.30, 95% CI 6.39-8.35) and those with alopecia (rOR 5.52, 95% CI 5.15-5.91) reported more cognitive dysfunctions than their counterparts., Conclusion: This study showed an increased reporting of cognitive dysfunction associated with finasteride use, especially among younger alopecia patients. Finasteride should be prescribed with caution, especially to younger alopecia patients.

Purpose: The efficacy and safety of vibegron, a β 3 -adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial., Materials and Methods: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs)., Results: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%)., Conclusions: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Hair loss is driven by multiple factors, including genetics. Androgenetic alopecia (AGA) is a condition in which treatments necessitate prolonged compliance with prescribed medications. We have developed IVL3001, a long-acting injectable (LAI) formulation of finasteride encapsulated within poly lactic-co-glycolic acid microspheres, to enhance the efficacy of the finasteride and to achieve consistent positive outcomes in adults. An open-label, sequential, single-dose phase I clinical trial was designed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) of IVL3001., Methods: A total of 40 non-smoking, healthy adult males were divided into three cohorts where the IVL3001 group received a single subcutaneous injection of 12-36 mg IVL3001 and 1 mg finasteride (Propecia ® ) once daily for 28 days. The plasma concentrations of finasteride, dihydrotestosterone (DHT), and testosterone were measured using liquid chromatography-tandem mass spectrometry. The tolerability of the injections was assessed, and compartment models were developed to predict the effective dose and assess PK/PD profiles., Results: IVL3001 and finasteride 1 mg tablets were well tolerated. IVL3001 showed consistent plasma concentrations without bursts or fluctuations. Consistent with its mechanism of action, IVL3001 reduced DHT levels. Simulation data showed that the administration of 12-36 mg of IVL3001 every 4 weeks achieved plasma concentrations similar to finasteride, with comparable DHT reduction., Conclusion: The present study represents the first clinical trial to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD), and tolerability of finasteride long-acting injectables (LAI) in adults. The rapid onset of action sustained effective drug concentration and the prolonged half-life of IVL3001 suggest that it offers multiple benefits over conventional oral formulations in terms of therapeutic response and compliance., Trial Registration: ClinicalTrials.gov identifier, NCT04945226., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Finasteride, a 5α-Reductase inhibitor, is used to treat male pattern baldness and benign prostatic hyperplasia. Several clinical studies show that chronic finasteride treatment induces persistent depression, suicidal thoughts and cognitive impairment and these symptoms are persistent even after its withdrawal. Previous results from our lab showed that repeated administration of finasteride for six days induces depression-like behavior. However, whether short-term finasteride administration induces anxiety-like behavior and memory impairment and alters synaptic plasticity are not known, which formed the basis of this study. Finasteride was administered to 2-2.5 months old male Wistar rats for six days and subjected to behavioral evaluation, biochemical estimation and synaptic plasticity assessment. Anxiety-like behavior was evaluated in the elevated plus maze (EPM), open field test (OFT), light/dark test (LDT), and novelty suppressed feeding test (NSFT), and learning and memory using novel object recognition test (NORT) and novel object location test (NOLT) and depression-like behavior in the sucrose preference test (SPT). Synaptic plasticity in the hippocampal Schaffer collateral-CA1 was evaluated using slice field potential recordings. Plasma corticosterone levels were estimated using ELISA. Finasteride administration induced anxiety-like behavior in the EPM, OFT, LDT and NSFT, and depression-like behavior in the SPT. Further, finasteride induced hippocampal dependent spatial learning and memory impairment in the NOLT. In addition, finasteride decreased basal synaptic plasticity and long-term potentiation (LTP) in the hippocampus. A trend of increased plasma corticosterone levels was observed following repeated finasteride administration. These results indicate the potential role of corticosterone and synaptic plasticity in finasteride-induced effects and further studies will pave way for the development of novel neurosteroid-based therapeutics in neuropsychiatric diseases., Competing Interests: Declaration of competing interest The authors do not have any conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Prior literature has suggested that finasteride may negatively impact men's sexual health. In 2011, the Food and Drug Administration (FDA) provided a warning on finasteride drug labels to incorporate sexual side effects such as reduced libido and erectile dysfunction. We aimed to evaluate global online interest in finasteride sexual side effects, their penetrance and variation, and how they compared overtime. We also aimed to evaluate the influence of the FDA label warnings on web-based searches for finasteride side effects. We utilized Google search engine from January 2004 to December 2020 to include separate trends from web searches of "Propecia," "Propecia side effects," "finasteride", "finasteride side effects", and "post-finasteride syndrome" compared amongst the United States, United Kingdom, and Australia. We performed join-point regression analysis. We compared the annual relative search volume (ARSV) and annual percentage change (APC) to evaluate for loss or gain of interest in the respective key terms. We determined that the average ARSV for "finasteride" was 14.8% in 2004 and increased significantly to 57.3% in 2020 (APC: +9.25%, 95% CI 8 to 10.5, p < 0.001). Likewise, there was significant increased interest in "finasteride side effects" (APC: +20.7, p < 0.001) and "post-finasteride syndrome" (APC: +29.2; p < 0.001) in the United States overtime. Finally, when we compared trends before and after the FDA warnings, the average ASRV of "finasteride", "finasteride side effects", and "post-finasteride syndrome" all increased significantly (p = 0.001, p = 0.014, p < 0.001), respectively. Thus, it is evident that there is a global web-based interest in finasteride and its sexual health side effects, particularly after the FDA warning in 2011. There is boosted public awareness, and thus providers should have more detailed and careful conversations with patients prior to starting a 5α-reductase inhibitor such as finasteride., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Prior studies indicate that neuroactive steroids mediate some of alcohol's effects. Dutasteride, widely used to treat benign prostatic hypertrophy, is an inhibitor of 5-alpha reductase enzymes, which play a central role in the production of 5α-reduced neuroactive steroids. The purpose of this study was to test dutasteride's tolerability and efficacy for reducing drinking., Methods: Men (n = 142) with heavy drinking (>24 drinks per week) and a goal to either stop or reduce drinking to nonhazardous levels were randomized to placebo or 1 mg dutasteride daily for 12 weeks. We hypothesized that dutasteride-treated patients would be more successful in reducing drinking., Results: Generalized linear mixed models that included baseline drinking, treatment, time and their 2-way interaction identified significant interactions of treatment-time, such that dutasteride treatment reduced drinking more than placebo. During the last month of treatment, 25% of dutasteride-treated participants had no hazardous drinking (no heavy drinking days and not more than 14 drinks per week) compared with 6% of placebo-treated participants (P = 0.006; NNT = 6). Sensitivity analysis identified baseline drinking to cope as a factor associated with larger reductions in drinking for dutasteride compared with placebo-treated participants. Dutasteride was well tolerated. Adverse events more common in the dutasteride group were stomach discomfort and reduced libido., Conclusion: Dutasteride 1 mg daily was efficacious in reducing the number of heavy drinking days and drinks per week in treatment-seeking men. The benefit of dutasteride compared with placebo was greatest for participants with elevated baseline drinking to cope motives., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2024 Japanese Dermatological Association.)

Despite its efficacy for treating androgenetic alopecia, finasteride, an inhibitor of 5α-reductase (i.e., the enzyme converting testosterone, T, into dihydrotestosterone, DHT), is associated with several side effects including sexual dysfunction (e.g., erectile dysfunction). These side effects may persist after drug suspension, inducing the so-called post-finasteride syndrome (PFS). The effects of subchronic treatment with finasteride (i.e., 20 days) and its withdrawal (i.e., 1 month) in rat corpus cavernosum have been explored here. Data obtained show that the treatment was able to decrease the levels of the enzyme 5α-reductase type II in the rat corpus cavernosum with increased T and decreased DHT levels. This local change in T metabolism was linked to mechanisms associated with erectile dysfunction. Indeed, by targeted metabolomics, we reported a decrease in the nitric oxide synthase (NOS) activity, measured by the citrulline/arginine ratio and confirmed by the decrease in NO 2 levels, and a decrease in ornithine transcarbamylase (OTC) activity, measured by citrulline/ornithine ratio. Interestingly, the T levels are negatively correlated with NOS activity, while those of DHT are positively correlated with OTC activity. Finasteride treatment also induced alterations in the levels of other molecules involved in the control of penile erection, such as norepinephrine and its metabolite, epinephrine. Indeed, plasma levels of norepinephrine and epinephrine were significantly increased and decreased, respectively, suggesting an impairment of these mediators. Interestingly, these modifications were restored by suspension of the drug. Altogether, the results reported here indicate that finasteride treatment, but not its withdrawal, affects T metabolism in the rat corpus cavernosum, and this alteration was linked to mechanisms associated with erectile dysfunction. Data here reported could also suggest that the PFS sexual side effects are more related to dysfunction in a sexual central control rather than peripheral compromised condition., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Introduction: Treating alopecia can be challenging. The available treatments are topical minoxidil, low-dose oral minoxidil (LDOM), and 5-α reductase inhibitors like finasteride and dutasteride. Only topical minoxidil and finasteride 1 mg daily are FDA-approved, while the rest are used off-label. Recent research has suggested that oral minoxidil may be a safe and effective treatment for both female androgenetic alopecia (female AGA) and male androgenetic alopecia (male AGA)., Areas Covered: In this review, we explore the pharmacokinetics, mechanism of action, safety, and efficacy of oral minoxidil. Additionally, we discuss its effectiveness compared to other treatments available for female AGA and male AGA., Expert Opinion: LDOM has demonstrated a favorable efficacy and safety profile in several trials. Subsequently, its use for the treatment of male AGA and female AGA is increasing. However, its use remains off-label, and through increased usage, we will get a better idea of the best dosage and monitoring guidelines. LDOM has also been used with some effectiveness in other forms of hair loss.

Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Post-finasteride syndrome and post-SSRI sexual dysfunction, are two poorly explored clinical conditions in which men treated for androgenetic alopecia with finasteride or for depression with SSRI antidepressants show persistent side effects despite drug suspension (e.g., sexual dysfunction, psychological complaints, sleep disorders). Because of some similarities in the symptoms, common pathological mechanisms are proposed here. Indeed, as discussed, clinical studies and preclinical data obtained so far suggest an important role for brain modulators (i.e., neuroactive steroids), neurotransmitters (i.e., serotonin, and cathecolamines), and gut microbiota in the context of the gut-brain axis. In particular, the observed interconnections of these signals in these two clinical conditions may suggest similar etiopathogenetic mechanisms, such as the involvement of the enzyme converting norepinephrine into epinephrine (i.e., phenylethanolamine N-methyltransferase). However, despite the current efforts, more work is still needed to advance the understanding of these clinical conditions in terms of diagnostic markers and therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Purpose of Review: Despite the widespread utilization of 5-alpha reductase inhibitors (5-ARIs) for managing benign prostatic hyperplasia (BPH), certain BPH patients exhibit unresponsiveness to 5-ARIs therapy. This paper provides a comprehensive overview of the current perspectives on the mechanisms of 5-ARIs resistance in BPH patients and integrates potential biomarkers and underlying therapeutic options for 5-ARIs resistance. These findings may facilitate the development of novel or optimize more effective treatment options, and promote personalized medicine for BPH., Recent Findings: The pathways contributing to resistance against 5-ARIs in certain BPH patients encompass epigenetic modifications, shifts in hormone levels, autophagic processes, and variations in androgen receptor structures, and these pathways may ultimately be attributed to inflammation. Promisingly, novel biomarkers, including intravesical prostatic protrusion, inflammatory factors, and single nucleotide polymorphisms, may offer predictive insights into the responsiveness to 5-ARIs therapy, empowering physicians to fine-tune treatment strategies. Additionally, on the horizon, GV1001 and mTOR inhibitors have emerged as potential alternative therapeutic modalities for addressing BPH in the future. After extensive investigation into BPH's pathological processes and molecular landscape, it is now recognized that diverse pathophysiological mechanisms may contribute to different BPH subtypes among individuals. This insight necessitates the adoption of personalized treatment strategies, moving beyond the prevailing one-size-fits-all paradigm centered around 5-ARIs. The imperative for early identification of individuals prone to treatment resistance will drive physicians to proactively stratify risk and adapt treatment tactics in future practice. This personalized medicine approach marks a progression from the current standard treatment model, emerging as the future trajectory in BPH management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: The most prescribed class of medications for benign prostatic hyperplasia (BPH) is α-blockers (ABs). However, the cardiovascular safety profile of these medications among patients with BPH is not well understood., Objective: To compare the safety of ABs vs 5-α reductase inhibitors (5-ARIs) for risk of adverse cardiovascular outcomes., Design, Setting, and Participants: This active comparator, new-user cohort study was conducted using insurance claims data from a 20% random sample of Medicare beneficiaries from 2007 to 2019 to evaluate the 1-year risk of adverse cardiovascular outcomes. Males aged 66 to 90 years were indexed into the cohort at new use of an AB or 5-ARI. Twelve months of continuous enrollment and at least 1 diagnosis code for BPH within 12 months prior to initiation were required. Data were analyzed from January 2007 through December 2019., Exposures: Exposure was defined by a qualifying prescription fill for an AB or 5-ARI after at least 12 months without a prescription for these drug classes., Main Outcomes and Measures: Follow-up began at a qualified refill for the study drug. Primary study outcomes were hospitalization for heart failure (HF), composite major adverse cardiovascular events (MACE; hospitalization for stroke, myocardial infarction, or death), composite MACE or hospitalization for HF, and death. Inverse probability of treatment and censoring-weighted 1-year risks, risk ratios (RRs), and risk differences (RDs) were estimated for each outcome., Results: Among 189 868 older adult males, there were 163 829 patients initiating ABs (mean [SD] age, 74.6 [6.2] years; 579 American Indian or Alaska Native [0.4%], 5890 Asian or Pacific Islander [3.6%], 9179 Black [5.6%], 10 610 Hispanic [6.5%], and 133 510 non-Hispanic White [81.5%]) and 26 039 patients initiating 5-ARIs (mean [SD] age, 75.3 [6.4] years; 76 American Indian or Alaska Native [0.3%], 827 Asian or Pacific Islander [3.2%], 1339 Black [5.1%], 1656 Hispanic [6.4%], and 21 605 non-Hispanic White [83.0%]). ABs compared with 5-ARIs were associated with an increased 1-year risk of MACE (8.95% [95% CI, 8.81%-9.09%] vs 8.32% [95% CI, 7.92%-8.72%]; RR = 1.08 [95% CI, 1.02-1.13]; RD per 1000 individuals = 6.26 [95% CI, 2.15-10.37]), composite MACE and HF (RR = 1.07; [95% CI, 1.03-1.12]; RD per 1000 individuals = 7.40 [95% CI, 2.88-11.93 ]), and death (RR = 1.07; [95% CI, 1.01-1.14]; RD per 1000 individuals = 3.85 [95% CI, 0.40-7.29]). There was no difference in risk for HF hospitalization alone., Conclusions and Relevance: These results suggest that ABs may be associated with an increased risk of adverse cardiovascular outcomes compared with 5-ARIs. If replicated with more detailed confounder data, these results may have important public health implications given these medications' widespread use.

Background: Five-alpha reductase inhibitors (5αRIs) are used to treat benign prostatic hyperplasia (BPH). However, the cardiovascular effects of 5αRIs remain poorly understood. The study objective was to compare the rate of hospitalization for heart failure among men with BPH prescribed 5αRIs to that of men with BPH not prescribed BPH medications., Methods: Using the Clinical Practice Research Datalink linked with hospitalization and vital statistics data, we conducted a population-based cohort study among patients newly diagnosed with BPH. We defined exposure as the current use of 5αRIs, current use of alpha-blockers, and no current use of BPH medications in a time-varying approach. The primary endpoint was hospitalization for heart failure, and secondary endpoints were myocardial infarction, stroke, and cardiovascular death. We used time-dependent Cox-proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Our cohort included 94,440 men with incident BPH. A total of 3893 hospitalizations for heart failure occurred over 527,660 person-years of follow-up (incidence rate 7.38; 95% CI, 7.15-7.61, per 1000 person-years). Compared with no current use of BPH medications, current use of 5αRIs was not associated with an increased risk of hospitalization for heart failure (HR 0.94; 95% CI, 0.86-1.03), myocardial infarction (HR 0.92; 95% CI, 0.81-1.05), stroke (HR 0.94; 95% CI, 0.85-1.05), or cardiovascular death (HR 0.89; 95% CI, 0.80-0.99)., Conclusions: The use of 5αRIs was not associated with an increased risk of hospitalization for heart failure, myocardial infarction, stroke, or cardiovascular death compared with non-use., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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%., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Tamsulosin and dutasteride are drugs widely used to treat benign prostatic hypertrophy. having a good safety profile. There are few reports of liver injury associated with the use of tamsulosin; however, there are no reports of hepatic toxicity from the use of dutasteride and the combined use of tamsulosin/dutasteride. We present the case of a 64-year-old man who developed liver injury after the combined use of tamsulosin/dutasteride, developing a pattern of hepatocellular damage and acute hepatitis symptoms. Viral, autoimmune, and metabolic storage diseases of the liver were ruled out, as well as biliary pathology by means of abdominal ultrasound and resonance cholangiography. In the causality evaluation, CIOMS-RUCAM presented: 6 points (probable) and Naranjo: 4 points (possible). The patient presented a clinical and laboratory response after discontinuing the drug.

Introduction: 5α-reductase inhibitors (5ARI) are commonly prescribed medications. There is ongoing controversy about the adverse events of these medications. The aim of this study is to characterize lawsuits in Canada involving medical complications of 5ARIs use., Materials and Methods: Legal cases were queried from CanLII. Cases were included if they involved a party taking a 5ARI who alleged an adverse event. Relevant full cases were retained, and pertinent characteristics were extracted with the help of a legal expert., Results: Our deduplicated search yielded 67 unique legal documents from December 2013 to February 2019. Twelve of these documents met the inclusion criteria (representing 3 cases, considering each case had several hearings). The medical complaints filed by the plaintiffs were all related to medication side effects (n = 3, 100%). The plaintiffs were commonly patients themselves. Defendants were exclusively pharmaceutical companies. Persistent erectile dysfunction after stopping the medication was cited as a side effect in all complaints. The prescriptions were made for male pattern hair loss (n = 3, 100%) in all cases. All cases represent class actions brought by the plaintiffs, and they have been certified by their respective court. However, the cases are still ongoing., Conclusion: While 5ARI use has been linked to undesired sexual side effects, there have been few litigations on this issue in Canada. Persisting sexual dysfunction after stopping the medication is the only complaint presented in legal action. To date, no judgment against a physician or pharmaceutical company was identified. Cases are still ongoing.

Importance: Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality., Objective: To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality., Data Sources: A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases., Study Selection: Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies., Data Extraction and Synthesis: This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022., Main Outcomes and Measures: The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline., Results: Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen-adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08)., Conclusions and Relevance: This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.

Background/aim: The clinical hazard of prostate cancer development after five-alpha reductase inhibitors (5ARI) treatment among benign prostate hyperplasia (BPH) patients is still controversial. The aim of this study was to evaluate the epidemiological features of BPH patients treated in a single institute to identify risk factors associated with prostate cancer development., Patients and Methods: We retrospectively analyzed patients who were diagnosed with BPH and received alpha blockers (AB) only or 5ARI between January 2007 and December 2012 and followed up until death or December 2020. The primary study outcome was prostate cancer and high-grade prostate cancer., Results: Of the 5,122 included patients, 14.9% (762/5,122) received 5ARI during their BPH treatment. The median age, initial prostate specific antigen (PSA) levels and the PSA change were significantly higher in the 5ARI group compared to those of the AB group. The prostate cancer diagnosis rate was higher in the 5ARI group, and the percentage of high-grade prostate cancer was not different between the two groups. In total, 1,715 (33.5%) patients were recorded dead, and the median follow-up period was longer in the 5ARI group. In Cox regression analysis, only age and initial PSA levels were significantly associated with prostate cancer. Late PSA was the only independent factor associated with high-grade prostate cancer development., Conclusion: Our real-world data revealed that age, initial PSA, and late PSA levels were associated with prostate cancer and high-grade prostate cancer diagnosis among BPH patients. Furthermore, 5ARI use had no effect on prostate cancer patient survival. However, PSA assessment during follow-up is still required in our institutional practice to avoid delayed diagnosis., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Competing Interests: Conflicts of interest Dr Trinh reports personal fees from Astellas, Bayer, Janssen, Insightec, and Intuitive Surgical, outside the submitted work. Drs Bhojani, Elterman, and Zorn report consulting fees from Procept Robotics, Olympus, and BSC, outside of the submitted work. Dr Chughtai reports consulting fees from BSC, Olympus, Meditate, Ferring, and Urovant, outside of the submitted work. David-Dan Nguyen is supported by a Sexual Medicine Society of North America (SMSNA) Scholars in Sexuality Research Grant. All other authors have no conflicts of interest to declare.

Importance: In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for benign prostatic hyperplasia and androgenic alopecia. Numerous studies and reports have indicated associations of 5-ARIs with depression and suicide. However, most of these studies had methodological shortcomings, and very little is known about the potential association of 5-ARIs with dementia., Objective: To investigate the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide., Design, Setting, and Participants: This Swedish register-based cohort study included 2 236 876 men aged 50 to 90 years between July 1, 2005, and December 31, 2018. Statistical analyses were performed from September 15, 2021, to May 25, 2022., Main Outcomes and Measures: A diagnosis of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide., Exposures: A recorded prescription in the Swedish national prescription register of finasteride or dutasteride and duration of use., Results: Of 2 236 876 men (median age at the start of follow-up, 55 years [IQR, 50-65 years] and at treatment initiation, 73 years [IQR, 66-80 years]), 70 645 (3.2%) started finasteride treatment, and 8774 (0.4%) started dutasteride treatment. Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22 [95% CI, 1.17-1.28]; dutasteride: HR, 1.10 [95% CI, 1.01-1.20]), Alzheimer disease (finasteride: HR, 1.20 [95% CI, 1.10-1.31]; dutasteride: HR, 1.28 [95% CI, 1.09-1.50]), vascular dementia (finasteride: HR, 1.44 [95% CI, 1.30-1.58]; dutasteride: HR, 1.31 [95% CI, 1.08-1.59]), and depression (finasteride: HR, 1.61 [95% CI, 1.48-1.75]; dutasteride: HR, 1.68 [95% CI, 1.43-1.96]). However, the magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over 4 years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride. In contrast, 5-ARIs were not associated with suicide (finasteride: HR, 1.22 [95% CI, 0.99-1.49]; dutasteride: HR, 0.98 [95% CI, 0.62-1.54])., Conclusions and Relevance: This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement. Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.

Background: Androgenetic alopecia (AGA) is the most common cause of hair loss, often challenging to treat. While oral finasteride (1 mg/d) is an FDA-approved treatment for male AGA, oral minoxidil and oral dutasteride are not approved yet. However, clinicians have been increasingly using these two drugs off-label for hair loss. Recently, Japan and South Korea have approved oral dutasteride (0.5 mg/d) for male AGA., Efficacy and Safety: A probable efficacy ranking, in decreasing order, is - dutasteride 0.5 mg/d, finasteride 5 mg/d, minoxidil 5 mg/d, finasteride 1 mg/d, followed by minoxidil 0.25 mg/d. Oral minoxidil predominantly causes hypertrichosis and cardiovascular system (CVS) symptoms/signs in a dose-dependent manner, whereas oral finasteride and dutasteride are associated with sexual dysfunction and neuropsychiatric side effects., Pharmacokinetics and Pharmacodynamics: The average plasma half-lives of minoxidil, finasteride, and dutasteride are ∼4 h, ∼4.5 h, and ∼5 weeks, respectively. Minoxidil acts through multiple pathways to promote hair growth. It has been shown as a vasodilator, an anti-inflammatory agent, a Wnt/β-catenin signaling inducer, and an antiandrogen. Finasteride inhibits 5α-reductase (5AR) type II isoenzyme, while dutasteride inhibits both type I and type II. Thus, dutasteride suppresses DHT levels more than finasteride in the serum and scalp.

5-α reductase inhibitors (5αRIs) are effective for the treatment of benign prostatic hyperplasia (BPH). However, 5αRIs could lower levels of haemoglobin, increasing the risk of anaemia. The objective of this study was to compare the rate of anaemia between new users of 5αRIs and α-blockers in the UK., Methods: We conducted a matched, active comparator, new-user cohort study using the Clinical Practice Research Datalink. The study population consisted of men aged ≥40 years with incident BPH who initiated 5αRIs between 1998 and 2019 and were matched 1:1 on propensity score to new users of α-blockers. Anaemia was defined by a measured haemoglobin <130 g/L. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for anaemia., Results: Our study cohort included 9429 new users of 5αRIs and 9429 matched new users of α-blockers. Their median durations of follow-up were 136 days (interquartile range: 54-336 d) and 77 days (interquartile range: 58-236 d), respectively. A total of 2865 5αRIs users and 2407 α-blocker users developed incident anaemia, representing rates of 37.3 (95% CI: 33.6-41.3) and 42.0 (95% CI: 38.1-46.2) per 100 person-years, respectively. The use of 5αRIs was not associated with an increased risk of anaemia compared to the use of α-blockers (HR: 0.95, 95% CI: 0.90-1.00). Similarly, we did not observe an increased risk of mild, moderate, or severe anaemia., Conclusion: The use of 5αRIs was not associated with an increased risk of anaemia compared to the use of α-blockers among men with BPH., (© 2022 British Pharmacological Society.)

Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64-2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74-2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80-2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians., Competing Interests: None

Introduction and Objectives: Post-finasteride syndrome (PFS) is a little known adverse effect of 5α-reductase inhibitor (5-ARI) drugs used in benign prostatic hyperplasia (BPH) and androgenetic alopecia. Five articles on the syndrome have been published in Spain, although no review has been published.The objectives of this article are to review the world literature, including the Spanish literature., Material and Methods: A retrospective review on post-finasteride syndrome was performed between 2011 and 2020. The search for information in PubMed/Medline was performed using the English terms "post-finasteride, post-finasteride syndrome" and in Google with the Spanish "post-finasteride, síndrome post-finasteride". The results of the variables studied were analyzed using descriptive statistics., Results: A total of 64 worldwide articles on post-finasteride syndrome were found, discarding 24 (37.5%) that did not deal with the symptoms of the syndrome, and 40 articles (62.5%) by 37 authors were included for study, corresponding to 29 publications on case series (72.5%) and 11 reviews (27.5%). Of the 40 articles, 37 referred to male post-finasteride syndrome (92.5%) and 3 to female (7.5%), the number of patients studied in the review was 87,887 corresponding to 87,224 men (99.2%) and 663 women (0.7%), with the number of articles on general symptoms being 23 (57.5%), male sexual symptoms 20 (50%) and female sexual symptoms 1 (2.5%). The articles came from 14 specialties, with Dermatology 14 publications (35%), Urology-Andrology 7 (17.5%) and Pharmacology 6 (15%). The countries with the highest number of publications were the USA 15 (37.5%), Italy 7 (17.5%) and Spain 5 (12.5%)., Conclusions: Finasteride is rarely associated with sexual and systemic adverse effects that constitute the so-called post-finasteride syndrome. There are still few studies on this syndrome in the world. This is the first review of this syndrome in Spain.

Decades after the introduction of 5α-reductase inhibitors and α1-adrenoceptor antagonists, new data of practical relevance related to their desired and adverse effects continues to emerge. Some of these novel findings are to be taken seriously but are insufficiently established, for instance associations between drug use and depression or dementia. Multiple combination treatments have been tested. While combination treatment was often statistically superior to monotherapy, the difference was mostly in the range of 1 IPSS point, which raises doubts on the clinical relevance of the findings at the group level. The new evidence enables further personalisation of the treatment of male lower urinary tract dysfunction, but also makes individual risk-benefit considerations more complex., Competing Interests: MCM ist Berater und/oder Referent für Apogepha, Astellas, Dr. Willmar Schwabe und GSK. SM ist Berater und/oder Referent für Astellas, Boston Scientific, Genericon und GSK., (Thieme. All rights reserved.)

Background and Objectives: Finasteride 1 mg/day is indicated for androgen-dependent conditions such as male androgenetic alopecia (AGA)., Methods: The literature is comprehensively summarized on the pharmacodynamics, pharmacokinetics, mechanism of action, and metabolism of finasteride. Pairwise and network meta-analyses were performed to assess the efficacy of finasteride reported in clinical trials. The adverse events profile is described along with the post-marketing reports., Results and Conclusion: Finasteride 1 mg/day significantly increased total hair count compared to placebo after 24 weeks (mean difference = 12.4 hairs/cm 2 , p  < .05), and 48 weeks (mean difference = 16.4 hairs/cm 2 , p  < .05). The efficacy of the two doses of finasteride (5 mg/day and 1 mg/day) and topical finasteride (1% solution) were not significantly different. The most commonly reported sexual events include erectile dysfunction and decreased libido. Increasing patient complaints and analysis of the FAERS database led to the inclusion of depression in the FDA label in 2011, as men were found to be at a risk of suicide due to the persistent sexual side effects, commonly termed as post-finasteride syndrome. Finasteride is shown to be reasonably tolerated in both men and women; however, patients need to be educated about the possible short- and long-term side-effects.

Background: One of the most prescribed treatments for benign prostatic hyperplasia (BPH) is 5α-reductase inhibitors (5ARI). Europe experienced recent safety issues involving 5ARI and depression symptoms, with similar findings being seen in Western countries. The South Korea has updated the drug label in accordance with European recommendations, but the relevant evidence was insufficient. This study compared the use of 5ARI versus α-blocker (AB) as a treatment for BPH and related risks of depression to provide evidence based on the Korean population., Methods: This was a retrospective cohort study using South Korea's Health Insurance Review & Assessment Service claim data from 2011 to 2017. New patients diagnosed in men with BPH and taking medications that contained either 5ARI or AB between July 1, 2013, and June 30, 2015, were included (n = 1,461 5ARI; n = 18,650 AB). The primary outcome was depression defined per the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10: F32-34, F38, F412, F432). Logistic regression was used to implement 1:1 propensity score (PS) matching of patients taking 5ARI to those taking AB to adjust for confounding. Cox proportional hazard models were used to compare the risk of depression associated with 5ARI versus AB., Results: Balance in baseline characteristics between the treatment groups were achieved within PS matched pairs (1,461 pairs). Compared to the AB medication group, the 5ARI group had lower depression (HR: 0.69, 95% CI: [0.51-0.92]). However, we could not find a clinically relevant, statistical difference after PS matching (HR: 0.91, 95% CI: [0.61-1.36])., Conclusions: The risk of depression associated with 5ARI was not meaningfully different from AB in Korea, which suggests that medical officials should provide the most appropriate medication for BPH patients by considering both treatment benefits and depression risk., Competing Interests: The authors declare that they have no competing interests.

Background: 5α-reductase inhibitors are commonly prescribed medications with multiple side effects used in the treatment of male pattern hair loss and benign prostatic hyperplasia. These side effects including "post-finasteride syndrome" may result in lawsuits., Objectives: To characterize lawsuits involving the adverse side effects of 5α-reductase inhibitor to better understand drivers of litigation and outcomes., Methods: Legal cases were queried from Nexis Uni using the search terms "5-alpha reductase inhibitor" as well as specific agents "finasteride," "dutasteride" in combination with "malpractice," "negligence," "damage," "loss," "side effect," and "complication." Secondary review was performed with publicly available data on "In Re: Propecia." Relevant cases were reviewed and pertinent characteristics were extracted and summarized using descriptive statistics., Results: Our search yielded 156 unique legal cases in the Nexis Uni database from April 2003 to May 2021. Only 18 of these cases met the inclusion criteria. Adverse events experienced by patients included medication side effects (n = 12, 66.7%), delayed cancer diagnosis (n = 3, 16.7%), and lack of symptom improvement (n = 3, 16.7%). The identity of the plaintiffs were most commonly patients themselves (n = 15, 83.3%). Defendants include pharmaceutical companies (n = 6, 33.3%), a combination of parties (n = 5, 27.8%), and physicians (n = 5, 27.8%) alone. The allegations included sexual side effects such as erectile dysfunction (n = 6, 33.3%) and decreased libido (n = 4, 22.2%). These prescriptions were made for benign prostatic hyperplasia (n = 9, 50%), male pattern hair loss (n = 7, 38.9%), and feminizing hormone therapy (n = 2, 11.1%). Several of these cases involved the same plaintiffs in related cases. No verdicts were against physicians. We noted a largely settled lawsuit involving more than 1000 plaintiffs with limited data on harms alleged and a $4.3 million settled amount. Of the total cases that resulted in a verdict, 9/18 were within the last 3 years., Discussion: The most common complications experienced by patients in our legal review were those involving sexual dysfunction with erectile dysfunction and decreased libido. The growing number of cases in the later years of our review suggests litigation may continue to increase in the coming future. Our review did not identify any individual cases that resulted in a monetary payout beyond a $4.3 million settlement outside of court., Conclusion: 5α-reductase inhibitor was alleged to have sexual, mental, and physical side effects, resulting in legal litigation. Despite this, no judgment against a physician or pharmaceutical company was identified. We do note and discuss a large number of lawsuits settled out of court. Given the increase in the number of lawsuits resulting in verdicts over the last 3 years, we suspect that the frequency of litigation around 5α-reductase inhibitors will continue for the foreseeable future., (© 2021 American Society of Andrology and European Academy of Andrology.)

Background: Androgenetic alopecia (AGA) is a frequently encountered dermatological concern that impacts a patient's self-esteem and quality of life. Finasteride is a selective 5-alpha reductase inhibitor that has been approved for the treatment of male AGA and the off-label use in female pattern hair loss (FPHL); however, its adverse effects may limit its use. Topical finasteride is a new formulation that aims to decrease complications caused by oral administration., Objective: This review assesses the pharmacology, current therapeutic use, and safety of topical finasteride for the treatment of AGA and FPHL., Methods: A PubMed search was conducted to include all English language articles on topical finasteride from January 1992 to January 2020., Results: A total of 33 articles including 28 topical finasteride related articles and five AGA related articles were included in this review. Multiple studies on topical finasteride as the treatment for male AGA and FPHL showed positive results with a favorable safety profile., Conclusions: Topical finasteride is a promising therapeutic option. We emphasize the importance of continued research for the establishment of a novel therapeutic agent.

Objective: To assess the use and safety of free combination therapy (dutasteride and tamsulosin), dutasteride monotherapy, or tamsulosin monotherapy in patients with benign prostatic hyperplasia (BPH)., Methods: This non-interventional retrospective cohort study used claims data from the Korea Health Insurance Review and Assessment-National Patient Sample database. Patients with BPH ≥ 40 years of age receiving combination therapy (dutasteride 0.5 mg and tamsulosin 0.4 mg daily) or dutasteride 0.5 mg, or tamsulosin 0.4 mg daily dose between 2012 and 2017 were included. The frequency, duration of treatment and risk of any adverse event (AE) or serious AE (SAE) was compared for combination therapy versus each monotherapy using non-inferiority testing., Results: Of 14,755 eligible patients, 1529 (10.4%) received combination therapy, 6660 (45.1%) dutasteride monotherapy, and 6566 (44.5%) tamsulosin monotherapy. The proportion of patients treated with combination therapy exceeded the pre-specified 3% threshold for 'frequent' use. Safety results indicated a similar risk of any AE and SAE irrespective of treatment group. The adjusted relative risk for any AE over the treatment observation period comparing combination therapy with dutasteride monotherapy was 1.07 (95% confidence interval [CI] 1.03, 1.12), and with tamsulosin monotherapy was 0.98 (95% CI 0.95, 1.02) demonstrating non-inferiority. The adjusted relative risk for any SAE was 1.07 (95% CI 0.66, 1.74) and 0.90 (95% CI 0.56, 1.45), compared with dutasteride and tamsulosin monotherapy, respectively. Although the SAE results did not statistically demonstrate non-inferiority of combination therapy based on pre-specified margins, the 95% CI for the risk ratio estimates included the null with a lower limit below the non-inferiority margins, indicating no meaningful differences in SAE risk between groups. Absolute SAE risks were low., Conclusion: Combination therapy with dutasteride and tamsulosin is frequently used in real-world practice in South Korea for treatment of BPH and demonstrates a safety profile similar to either monotherapy., (© 2021. The Author(s).)

Recent literature connects 5-alpha reductase inhibitors (5-ARIs) with neuropsychiatric adverse effects. Several clinical studies have indicated that former 5-ARIs users had a higher incidence of depressive symptoms and neuropsychiatric side effects than non-users. However, the underlying mechanisms involved in the depression in former 5-ARIs patients, a condition known as "post finasteride syndrome (PFS)", are not thoroughly understood. This review aims to summarize and discuss the association between 5-ARIs and depression as well as possible mechanisms. We used PubMed search terms including "depression", "depressive symptoms", "MDD", "anxiety", or "suicidal idea", and "5-alpha reductase inhibitors", "finasteride", "dutasteride", "5-ARIs". All relevant articles from in vivo and clinical studies from 2002 to 2021 were carefully reviewed. Any contradictory findings were included and debated. The potential mechanisms that link 5-ARIs and depression include alteration in neuroactive steroids, dopaminergic dysfunction, reduced hippocampal neurogenesis, increased neuroinflammation, alteration of the HPA axis, and epigenetic modifications. From this review, we hope to provide information for future studies based on animal experiments, and potential therapeutic strategies for depressive patients with PFS., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ejaculatory dysfunction is not only psychologically distressing but can become a significant obstacle for men who wish to conceive. Dysfunction comes in the form of anejaculation, reduced ejaculation, retrograde ejaculation, painful ejaculation, or premature ejaculation. Most treatments for lower urinary tract symptoms related to benign prostatic hyperplasia, which commonly occurs in aging men, carry significant risks of absent, reduced, or retrograde ejaculation. This review focuses on such risks that accompany both the medical and surgical management of lower urinary tract symptoms/benign prostatic hyperplasia and how these risks impact male fertility., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: An organic etiology underpinning post-finasteride syndrome, a constellation of persistent sexual, neuropsychiatric, and somatic symptoms reported by men exposed to 5-alpha-reductase inhibitors (5ARIs), is debated. Persistent changes in neurosteroid levels or androgen receptor expression have been implicated., Aim: To determine whether differences in gene expression, especially in relevant biologic pathways, exist between patients reporting post-finasteride syndrome symptoms and healthy controls., Methods: This was a single center, prospective case-control study taking place between March 2013 and September 2018. Men 18 years and older being evaluated for sexual dysfunction (study) or circumcision (control) were eligible for inclusion. Twenty-six men with a history of 5ARI use reporting symptoms consistent with post-finasteride syndrome were included in the patient group. Twenty-six men consented to inclusion in the control group., Outcomes: The primary outcome measure is gene expression data for genes affecting neurosteroid levels and androgen receptor activity from penile skin cells., Results: Gene expression of cells from penile skin samples from twenty-six men of median age 38 years (IQR, 33-42) in the study group was compared with that from twenty-six men of median age 41 years (IQR, 35-62) in the control group (P = .13), with 1,446 genes significantly over-expressed and 2,318 genes significantly under-expressed in study patients. Androgen receptor expression was significantly higher in study patients compared to controls (9.961 vs 9.494, adjusted P value = .01). Serum levels of androgen receptor activity markers 5α-androstanediol (0.950 ng/mL [0.749-1.587] vs 0.949 [0.817-1.337], P = .34) or 3α-androstanedione (3.1 ng/mL [1.925-5.475] vs 6.7 [3.375-11.4], P = .31) revealed no significant differences. No significant differences were found between the number of trinucleotide repeats (21.5 [20-23.75], 22 [19-25], P = .94)., Clinical Implications: In this study we present evidence of gene expression correlating with observed biologic differences in patients with post-finasteride syndrome; providers who prescribe 5ARIs should be aware and advise their patients accordingly., Strengths & Limitations: Strengths of this study include the evaluation of multiple proposed etiologies for post-finasteride syndrome. The study is also strengthened by the fact that not all data matched the initial hypotheses, qualifying the argument for the existence of PFS. Limitations include potential selection bias arising from more severe phenotypes seeking care; lack of gene expression data prior to 5ARI exposure; lack of non-penile tissue samples supposedly involved; and a lack of mechanistic data to imply causality., Conclusion: This study is the first to consider and demonstrate gene expression differences in patients with PFS as a potential etiology of sexual dysfunction. Howell S, Song W, Pastuszak A, et al. Differential Gene Expression in Post-Finasteride Syndrome Patients. J Sex Med 2021;18:1479-1490., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Primum non nocere. As physicians, our goal is to treat illnesses and alleviate suffering; however, in doing so, we can generate new problems in a game of medical whack-a-mole. For some patients, certain consequences or side effects are tolerable, while others may believe they have no alternative. For a male patient with infertility, a thorough history is imperative to elucidate whether the patient has been or is currently being exposed to medications that will harm libido, spermatogenesis, ejaculation, or the hypothalamic-pituitary-testosterone axis. This article will review the most common medications causing iatrogenic male infertility as well as options to minimize or even reverse their impact., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: To prospectively evaluate the detection rate of prostate cancer, and to identify the risk factors of prostate cancer detection after a 1-year administration of dutasteride and first negative prostate biopsy., Methods: Patients with benign prostatic hyperplasia who presented high prostate-specific antigen levels after the first negative prostate biopsy were administered 0.5 mg dutasteride daily for 1 year. They underwent a repeat prostate biopsy after 1 year. The primary end-point was the detection rate of prostate cancer. The secondary end-point was the ability of prostate-specific antigen kinetics to predict prostate cancer detection. Prostate-specific antigen was measured before the initial prostate biopsy and at 6, 9 and 12 months after starting dutasteride. Patients were classified into a prostate cancer and a non-prostate cancer group., Results: Prostate cancer was detected in 15 of 149 participants (10.1%). The total prostate-specific antigen change between the prostate cancer and non-prostate cancer group at 1 year was significantly different (P = 0.002). Although prostate-specific antigen levels at baseline did not significantly differ between study groups (P = 0.102), prostate-specific antigen levels at 6, 9 and 12 months were significantly different (P = 0.002, P = 0.001 and P < 0.001, respectively). The mean reduction rate of prostate-specific antigen density between the prostate cancer and non-prostate cancer group at 1 year was significantly different (-4.25 ± 76.5% vs -38.0 ± 28.7%, P = 0.001). Using a multivariate analysis, a >10% increase of prostate-specific antigen density at 1 year post-dutasteride treatment was the only predictive risk factor for prostate cancer after the first negative prostate biopsy (odds ratio 11.238, 95% confidence interval 3.112-40.577, P < 0.001)., Conclusion: In the present study cohort, >10% increase in prostate-specific antigen density represented the only significant predictive risk factor for prostate cancer diagnosis in patients with elevated prostate-specific antigen after the first negative prostate biopsy., (© 2021 The Japanese Urological Association.)

Purpose: Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort., Methods: Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects., Results: Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing β-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control., Conclusion: Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

Purpose: Increased risk of cardiac failure with α-blockers in hypertension studies and 5-alpha reductase inhibitors in prostate studies have raised safety concerns for long term management of benign prostatic hyperplasia. The objective of this study was to determine if these medications are associated with an increased risk of cardiac failure in routine care., Materials and Methods: This population based study used administrative databases including all men over 66 with a diagnosis of benign prostatic hyperplasia between 2005 and 2015. Men were categorized based on 5-alpha reductase inhibitor exposure and/or α-blocker exposure with a primary outcome of new cardiac failure utilizing competing risk models. Explanatory variables examined included exposure thresholds, formulations, age, and comorbidities associated with cardiac disease., Results: The data set included 175,201 men with a benign prostatic hyperplasia diagnosis with 8,339, 55,383, and 41,491 exposed to 5-alpha reductase inhibitor, α-blocker and combination therapy, respectively. Men treated with 5-alpha reductase inhibitor and α-blocker, alone or in combination, had a statistically increased risk of being diagnosed with cardiac failure compared to no medication use. Cardiac failure risk was highest for α-blockers alone (HR 1.22; 95% CI 1.18-1.26), intermediate for combination α-blockers/5-alpha reductase inhibitors (HR 1.16; 95% CI 1.12-1.21) and lowest for 5-alpha reductase inhibitors alone (HR 1.09; 95% CI 1.02-1.17). Nonselective α-blocker had a higher risk of cardiac failure than selective α-blockers (HR 1.08; 95% CI 1.00-1.17)., Conclusions: In routine care, men with a benign prostatic hyperplasia diagnosis and exposed to both 5-alpha reductase inhibitor and α-blocker therapy had an increased association with cardiac failure, with the highest risk for men exposed to nonselective α-blockers.