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Prostate International Dec 2022Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health...
OBJECTIVES
Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health concern in the aging population. The purpose of this study is to identify modifiable factors, which would prevent or delay BPH development.
METHODS
The association between BPH marker drugs and climate-, socioeconomic-, health condition-, and lifestyle habits-related variables was investigated by analyzing nationwide datasets which were collected in 2018, aggregated by prefecture (administrative unit), and published by Japanese ministries. Uroselective α receptor blockers and dutasteride were used as marker drugs referring to BPH prevalence. Correlation analysis, multiple linear regression analysis, and binomial logistic regression analysis were conducted with 47 Japanese prefectures as the unit.
RESULTS
The variables which showed || > 0.5 by correlation analysis were exercise habits ( = -0.5696), smoking habits ( = 0.6116), and daily drinking ( = 0.6001) for uroselective α receptor blockers, and antihypertensive medication ( = 0.5971), smoking habits ( = 0.6598), a small amount of drinking ( = -0.5292), and serum alanine aminotransferase ( = 0.6814) for dutasteride. Multiple linear regression equations were constructed by including these variables ( = 0.5453 for uroselective α receptor blockers and = 0.5673 for dutasteride). Binomial logistic regression analysis found a significant association between climate in the resident area and BPH development.
CONCLUSION
This ecological study, analyzing Japanese nationwide datasets, demonstrates that healthy lifestyle habits, especially avoidance of smoking, implementation of exercise in daily life, and a small amount of alcohol consumption, are important to prevent or delay BPH development. High blood pressure and high serum alanine aminotransferase are suggested as risk factors of BPH development.
PubMed: 36570647
DOI: 10.1016/j.prnil.2022.06.004 -
Translational Andrology and Urology Aug 2022The steroidal metabolism of abiraterone has been proposed to be involved in abiraterone resistance and limited approaches are available for abiraterone-resistant...
The clinical efficacy and limitations of dutasteride-regulated abiraterone metabolism in abiraterone-resistant patients: a prospective single-arm clinical trial in Chinese patients.
BACKGROUND
The steroidal metabolism of abiraterone has been proposed to be involved in abiraterone resistance and limited approaches are available for abiraterone-resistant patients. Dutasteride regulates abiraterone metabolism in patients and might enhance the clinical efficacy of abiraterone. However, the function of dutasteride to overcome abiraterone resistance has not been investigated in clinic. Here we investigated the clinical efficacy and limitations of dutasteride in patients with abiraterone-resistant prostate cancer.
METHODS
Abiraterone-resistant patients with metastatic castration-resistant prostate cancer (mCRPC) were enrolled in this single-arm, open-label study, patients were treated with dutasteride (0.5 mg/day), abiraterone (1,000 mg/day), and prednisone (5 mg twice daily), prostate-specific antigen (PSA) was tested monthly. The primary objective was PSA response, and the secondary objectives were to assess symptom relief and safety. Kaplan-Meier analysis was used to assess the PSA progression free survival (PSA-PFS) of patients.
RESULTS
Twenty-two patients (median age: 75 years) were enrolled, and 19 patients completed the treatment. After a median treatment of 4.0 months, 7 (37%) patients showed a slight PSA reduction (-2% to -32%), and the median PSA-PFS was 2.0 months (1-7 months). No significant improvement was observed in Eastern Cooperative Oncology Group (ECOG) performance status. Bone pain was relieved in 6 patients after 1 month of treatment, but the improvement was not significant. No grade 3 or grade 4 adverse events were observed.
CONCLUSIONS
The combination of dutasteride and abiraterone showed a mild effect in patients with abiraterone-resistant. The small sample size was the limitation of this study.
PubMed: 36092845
DOI: 10.21037/tau-22-507 -
Journal of Clinical Medicine May 2024The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral... (Review)
Review
The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol.
PubMed: 38892763
DOI: 10.3390/jcm13113052 -
BMC Urology Dec 2021To assess the use and safety of free combination therapy (dutasteride and tamsulosin), dutasteride monotherapy, or tamsulosin monotherapy in patients with benign...
Free combination of dutasteride plus tamsulosin for the treatment of benign prostatic hyperplasia in South Korea: analysis of drug utilization and adverse events using the National Health Insurance Review and Assessment Service database.
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.
Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-1 Receptor Antagonists; Adult; Aged; Databases, Factual; Drug Therapy, Combination; Dutasteride; Humans; Male; Middle Aged; Prostatic Hyperplasia; Republic of Korea; Retrospective Studies; Tamsulosin
PubMed: 34933674
DOI: 10.1186/s12894-021-00941-1 -
Translational Andrology and Urology Feb 2020The objective of this study is to review our 12-year experience with the 5-α reductase inhibitor dutasteride as a potential long-term treatment option for stuttering...
BACKGROUND
The objective of this study is to review our 12-year experience with the 5-α reductase inhibitor dutasteride as a potential long-term treatment option for stuttering priapism. Dutasteride has a uniquely long half-life of 35 days which offers a theoretical advantage as a chronic therapy for management of stuttering priapism.
METHODS
We retrospectively reviewed patients with stuttering priapism in our database from 2006-2018 treated with dutasteride. Men with concurrent use of medications other than dutasteride to treat stuttering priapism were excluded. Patients were started on a dose of 0.5 mg daily and tapered to a more infrequent dosing schedule, ranging from 0.5 mg every other day to once weekly. The frequency of priapism episodes before and after initiation of dutasteride therapy was analyzed.
RESULTS
Among 21 cases, 13 patients met our inclusion criteria (mean age 43 years). Median follow-up on daily dutasteride was 79 days, and median follow-up on tapered dutasteride was 607 days. A total of 11/13 (85%) men treated with dutasteride had some degree of improvement-5/13 (38%) had complete resolution of their symptoms and 6/13 (46%) had reduced frequency and/or severity of their episodes. Among 5/13 (38%) men who had >2 emergency room (ER) visits for ischemic priapism prior to therapy, most (3/5, 60%) did not require any ER visits while on dutasteride therapy. Among the five men who received chronic, tapered-dose therapy, all reported continued suppression of priapistic episodes. Among 4 patients with sickle cell disease (SCD), 3/4 (75%) ultimately chose more invasive therapy including androgen deprivation therapy (ADT) and penile prosthesis. Side effects were minimal and included gynecomastia (8%), decreased libido (8%), and fatigue (8%).
CONCLUSIONS
In patients with stuttering priapism, daily dutasteride therapy is a promising treatment option to reduce the frequency and severity of priapistic episodes without significant side effects. Therapy can effectively be tapered to once weekly dosing without a reduction in efficacy.
PubMed: 32055472
DOI: 10.21037/tau.2019.07.15 -
Pharmaceutics Sep 2022Lower Urinary Tract Symptoms (LUTs) in men are usually associated to benign prostatic hyperplasia (BPH), a non-malignant prostate enlargement. Unfortunately, BPH...
Lower Urinary Tract Symptoms (LUTs) in men are usually associated to benign prostatic hyperplasia (BPH), a non-malignant prostate enlargement. Unfortunately, BPH etiology is still unclear. Recent works highlighted a relevant inflammation role in BPH onset and development. Consequently, to complement the 5-α reductase (and α-adrenergic receptor agonists-based therapy, an anti-inflammatory therapy should be devised. To reduce potential adverse effects of multi-drug treatment, plant extract-based therapies are becoming increasingly common. Serenoa repens, the main phytotherapic treatment for BPH, is not sufficient to front the multi-faceted etiology of BPH. In response to this, a novel, multiple phytotherapic agents-based formulation, LENILUTS, was developed. In the present work, we compared, using an in vitro approach, the prostatic safety and efficacy of LENILUTS with a commercial formulation, based only on Serenoa repens, and a 5αR inhibitor, Dutasteride. Furthermore, preliminary in vitro experiments to investigate the active principles, bioaccessibility and bioavailability of LENILUTS were performed. Our results showed a better prostatic safety and therapeutic efficacy of LENILUTS compared to the commercial formulation and Dutasteride, with increased anti-inflammatory, and pro-apoptotic activity, and a stronger inhibitory effect on the release of the key enzyme 5αR and Prostatic-Specific Antigen (PSA). The limited bioaccessibility and bioavailability of the active principles of LENILUTS were highlighted. Considering the results obtained, the LENILUTS formulation is more promising for BPH and LUTs therapy compared to formulations based on Serenoa repens only, but further efforts should be made to improve the bioaccessibility and bioavailability of the active principles.
PubMed: 36145614
DOI: 10.3390/pharmaceutics14091866 -
International Journal of Clinical... Jan 2020To evaluate real-world persistence and adherence in patients with benign prostate hyperplasia (BPH) receiving a fixed-dose combination of dutasteride plus tamsulosin... (Observational Study)
Observational Study
Persistence and adherence to dutasteride/tamsulosin fixed-dose versus free-combination alpha blocker/5ARI therapy in patients with benign prostate hyperplasia in Germany .
OBJECTIVE
To evaluate real-world persistence and adherence in patients with benign prostate hyperplasia (BPH) receiving a fixed-dose combination of dutasteride plus tamsulosin (DUT-TAM FDC) versus α-blocker plus 5-α reductase inhibitor (AB/5ARI) free-combination therapy.
MATERIALS AND METHODS
This retrospective, observational cohort study utilized the German IMS LRx (IQVIA) database. Patients ≥ 45 years old with BPH receiving DUT-TAM FDC or AB/5ARI free-combination therapy from July 1, 2011 to November 30, 2017 were included. Data were analyzed for 48 months from index date (date of first prescription). Persistence, measured as time to discontinuation (defined as a 90-day gap in therapy), was evaluated using Kaplan-Meier curves (log-rank tests). Adherence, measured as medication possession ratio (MPR), was based on a comparison of mean prescribing duration and expected treatment duration.
RESULTS
A total of 141,667 patients were included (DUT-TAM FDC, n = 86,057; free AB/5ARI: n = 55,610). Small differences in persistence were observed between treatment arms. At month 12, 41.8% of DUT-TAM FDC-treated and 41.0% of AB/5ARI free-combination therapy-treated patients were persistent; at month 24, 28.2% and 27.1% were persistent, respectively. A higher proportion of DUT-TAM FDC-treated patients had MPR ≥ 0.80, ≥ 0.75 and ≥ 0.70 compared with AB/5ARI free-combination therapy (p < 0.0001).
CONCLUSION
Small differences observed in persistence between treatment arms may not translate to meaningful clinical relevance. Adherence was significantly better in the FDC arm, which may be clinically relevant as improved adherence is associated with better outcomes. Persistence and adherence to BPH therapy in Germany is low; further studies exploring the reasons behind this are required.
Topics: 5-alpha Reductase Inhibitors; Drug Therapy, Combination; Dutasteride; Germany; Humans; Male; Medication Adherence; Middle Aged; Prostatic Hyperplasia; Retrospective Studies; Tamsulosin
PubMed: 31670653
DOI: 10.5414/CP203549 -
BMC Endocrine Disorders Sep 2020Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a...
BACKGROUND
Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2.
MAIN TEXT
While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed.
CONCLUSION
While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.
Topics: Anti-Inflammatory Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Dexamethasone; Drug Repositioning; Endocrine System; Humans; Pandemics; Pneumonia, Viral; Prognosis; SARS-CoV-2
PubMed: 32993622
DOI: 10.1186/s12902-020-00626-0 -
Prostate International Jun 2020The aim of this research is to study the influence of simultaneous taking of tadalafil and solifenacin in standard and double dosage on the lower urinary tract symptoms...
Improvement of the symptoms of lower urinary tract and sexual dysfunction with tadalafil and solifenacin after the treatment of benign prostatic hyperplasia with dutasteride.
BACKGROUND
The aim of this research is to study the influence of simultaneous taking of tadalafil and solifenacin in standard and double dosage on the lower urinary tract symptoms (LUTS) and sexual dysfunction in men with benign prostatic hyperplasia after the course of dutasteride.
MATERIALS AND METHODS
The research included 326 patients older than 50 years with benign prostatic hyperplasia coupled with LUTS and sexual dysfunction having undergone the course of treatment with dutasteride. After random division into three groups, patients from the Group A ( = 107) got tadalafil 5 mg/d as monotherapy, from the Group В ( = 107) got tadalafil 5 mg/d and solifenacin 10 mg/d, and from the Group С ( = 112) got tadalafil 5 mg/d and solifenacin 20 mg/d. The duration of treatment was 12 weeks. The rating of sexual function was made with the questionnaires International Index of Erectile Function and other.
RESULTS
The results of rating of sexual function with the questionnaires MSHQ-EjD and International Index of Erectile Function correlated among themselves. According to MSHQ-EjD, overall rating of the sexual function increased in each of the three groups (A: 67.9 (12.4)/91.5 (10.4), ≤ 0.05; B: 72.4 (14.5)/102.6 (16.9), ≤ 0.05; C: 76.6 (16.3)/109.6 (15.6), ≤ 0.05). The level of hyperactivity symptoms decreased in Groups В and С (В: urgency -2.9 (0.7)/1.1 (0.6), ≤ 0.05; nocturia 2.7 (1.0)/0.7 (0.5), ≤ 0.05; C: urgency -2.5 (0.5)/0.8 (0.6), ≤ 0.05; nocturia -2.8 (0.6)/1.0 (0.5), ≤ 0.05), and it did not change in the Group A.
CONCLUSIONS
The use of tadalafil as monotherapy significantly improves the sexual function but does not affect overactive bladder symptoms. The combination therapy of tadalafil and solifenacin leads to dramatic improvement of sexual function and reversibility of detrusor hyperactivity symptoms.
PubMed: 32647644
DOI: 10.1016/j.prnil.2019.11.005 -
Cancer Reports (Hoboken, N.J.) Dec 2021Dutasteride has been shown to increase expression of the prostate-specific membrane antigen (PSMA) in prostate cancer cells in previous in vitro studies. This...
BACKGROUND
Dutasteride has been shown to increase expression of the prostate-specific membrane antigen (PSMA) in prostate cancer cells in previous in vitro studies. This 5-alpha-reductase inhibitor is commonly used for the treatment of symptomatic benign prostatic enlargement. The modulation of PSMA expression might affect PSMA-based prostate cancer imaging and therapy.
AIM
The purpose of this work was to further analyze concentration-dependent effects of Dutasteride on PSMA expression in a mouse xenograft model.
METHODS AND RESULTS
Four groups of mice bearing LNCaP xenografts were treated for 14 days with daily intraperitoneal injections of either vehicle control or different concentrations of Dutasteride (0.1, 1, 10 mg/kg). Total expression of PSMA, androgen receptor (AR), and caspase-3 protein was analyzed using immunoblotting (WES). In addition, PSMA, cleaved caspase-3 and Ki-67 expression was assessed and quantified by immunohistochemistry. Tumor size was measured by caliper on day 7 and 14, tumor weight was assessed following tissue harvesting. The mean PSMA protein expression in mice increased significantly after treatment with 1 mg/kg (10-fold) or 10 mg/kg (sixfold) of Dutasteride compared to vehicle control. The mean fluorescence intensity significantly increased by daily injections of 0.1 mg/kg Dutasteride (1.6-fold) as well as 1 and 10 mg/kg Dutasteride (twofold). While the reduction in tumor volume following treatment with high concentrations of 10 mg/kg Dutasteride was nonsignificant, no changes in AR, caspase-3, cleaved caspase-3, and Ki-67 expression were observed.
CONCLUSION
Short-term Dutasteride treatments with concentrations of 1 and 10 mg/kg significantly increase the total PSMA protein expression in a mouse LNCaP xenograft model. PSMA fluorescence intensity increases significantly even using lower daily concentrations of 0.1 mg/kg Dutasteride. Further investigations are needed to elucidate the impact of Dutasteride treatment on PSMA expression in patients.
Topics: 5-alpha Reductase Inhibitors; Animals; Antigens, Surface; Apoptosis; Cell Proliferation; Dutasteride; Gene Expression Regulation, Neoplastic; Glutamate Carboxypeptidase II; Humans; Male; Mice; Prostatic Neoplasms; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
PubMed: 34008909
DOI: 10.1002/cnr2.1418