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Scientific Reports Mar 2023Finasteride, a 5α-reductase inhibitor used in benign prostatic hyperplasia and androgenetic alopecia, has been associated with an increased suicidal risk, whereas it is...
Finasteride, a 5α-reductase inhibitor used in benign prostatic hyperplasia and androgenetic alopecia, has been associated with an increased suicidal risk, whereas it is unclear whether such risk is similar to that for another 5α-reductase inhibitor, dutasteride. We aimed to assess the risk of suicidal behaviours with finasteride relative to dutasteride. A nationwide cohort study was conducted using the French National Health Data System (SNDS). Men aged 50 years or older initiating finasteride 5 mg or dutasteride 0.5 mg in France between 01-01-2012 and 30-06-2016 were included and followed until outcome (suicide death identified from death certificate or self-harm hospitalisation), treatment discontinuation or switch, death, or 31-12-2016. Self-harm by violent means or resulting in admission to an intensive care unit were also examined. Cox proportional hazards models controlled for age and psychiatric and non-psychiatric conditions by inverse probability of treatment weighting (IPTW). Analyses were stratified according to psychiatric history. The study compared 69,786 finasteride new users to 217,577 dutasteride new users (median age: 72.0 years [Q1-Q3 = 64.5-80.2] vs. 71.1 [Q1-Q3 = 65.0-79.2]). During follow-up, 18 suicide deaths (0.57/1000 person-years) and 34 self-harm hospitalisations (1.08/1000) occurred among finasteride users versus 47 deaths (0.43/1000) and 87 hospitalisations (0.79/1000) among dutasteride users. Overall, finasteride was not associated with an increased risk of any suicidal outcome (IPTW-adjusted Hazard Ratio = 1.21 [95% Confidence Interval .87-1.67]), suicide death or self-harm hospitalisation. However, among individuals with a history of mood disorders, finasteride was associated with an increased risk of any suicidal outcome (25 versus 46 events; HR = 1.64 [95% CI 1.00-2.68]), suicide death (8 versus 10 events; HR = 2.71 [95% CI 1.07-6.91]), self-harm by violent means (6 versus 6 events; HR = 3.11 [95% CI 1.01-9.61]), and self-harm with admission to an intensive care unit (7 versus 5 events; HR = 3.97 [95% CI 1.26-12.5]). None of these risks was significantly increased among individuals without a psychiatric history. These findings do not support an increased risk of suicide with finasteride used in the treatment of benign prostatic hyperplasia. However, an increased risk cannot be excluded among men with a history of mood disorder, but this result based on a limited number of events should be interpreted with caution.
Topics: Male; Humans; Aged; Dutasteride; Finasteride; Prostatic Hyperplasia; Cohort Studies; Suicidal Ideation; Oxidoreductases
PubMed: 37002313
DOI: 10.1038/s41598-023-32356-3 -
The New England Journal of Medicine Aug 2010
Comparative Study
Topics: 5-alpha Reductase Inhibitors; Azasteroids; Dutasteride; Enzyme Inhibitors; Finasteride; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms
PubMed: 20842790
DOI: 10.1056/NEJMc1005498 -
The World Journal of Men's Health May 2024Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2...
PURPOSE
Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases.
MATERIALS AND METHODS
We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching.
RESULTS
A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44-1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67-1.14; p=0.310).
CONCLUSIONS
Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.
PubMed: 38772542
DOI: 10.5534/wjmh.230327 -
American Journal of Clinical and... 2023Herbal supplements are widely used to enhance prostate health. These supplements may contain several types of plant sterols, vitamins, and minerals. By weight, however,... (Review)
Review
Herbal supplements are widely used to enhance prostate health. These supplements may contain several types of plant sterols, vitamins, and minerals. By weight, however, plant sterols make up an abundant ingredient component, with saw palmetto extract or its primary component, beta-sitosterol, often comprising the most abundant sterol. Saw palmetto extract/beta-sitosterol has been shown to promote anti-tumorigenic processes in prostate cancer cells and rodent models of prostate cancer. It has also been shown to inhibit the 5α-reductase enzyme, thereby behaving similarly to finasteride and dutasteride, which are widely used to treat prostatic enlargement, or benign prostatic hyperplasia (BPH). The aim of this study is to critically examine , , and human clinical studies to assess the safety and clinical utility of herbal supplements containing saw palmetto extract/beta-sitosterol for prostate health. The results of this study suggest multiple mechanisms through which beta-sitosterol represses prostate cancer and , particularly through its pro-apoptotic effect on prostate epithelial cells. Multiple studies also show that beta-sitosterol significantly improves lower urinary tract symptoms (LUTS) associated with BPH, but to an extent that is generally less effective than that achieved by pharmaceutical grade alpha-adrenergic receptor antagonists or 5α-reductase inhibitors. This latter finding suggests that supplements containing beta-sitosterol might be most appropriate for younger men with minimal LUTS who don't wish to embark on a clinical drug regimen for BPH treatment.
PubMed: 38148931
DOI: No ID Found -
The Canadian Journal of Hospital... 2017Finasteride and dutasteride are competitive inhibitors of 5α-reductase enzymes and are commonly used to treat symptomatic benign prostatic hyperplasia (BPH). (Review)
Review
BACKGROUND
Finasteride and dutasteride are competitive inhibitors of 5α-reductase enzymes and are commonly used to treat symptomatic benign prostatic hyperplasia (BPH).
OBJECTIVE
To compare the efficacy and safety of finasteride and dutasteride in terms of clinically important outcomes.
DATA SOURCES
A literature search was performed using the search terms "prostatic hyperplasia", "prostatic hypertrophy", "dutasteride", "finasteride", "quality of life", "adverse drug reaction", and "mortality". The Embase, PubMed, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences Literature databases were searched from inception to December 2015.
STUDY SELECTION AND DATA EXTRACTION
Randomized controlled trials, quasi-randomized trials, and systematic reviews comparing finasteride with dutasteride, either as monotherapy or in combination with α-blockers, for treatment of men with BPH were included. The outcomes of interest included need for prostate-related surgery, episodes of acute urinary retention, withdrawals due to adverse events, number of patients experiencing serious adverse events, mortality, and sexual dysfunction.
DATA SYNTHESIS
Four studies involving a total of 1879 patients were included in the analysis. There were no significant differences in any of the clinically important outcomes examined: for prostate-related surgery, odds ratio (OR) 2.01 (95% confidence interval [CI] 0.18-22.24); for episodes of acute urinary retention, OR 1.47 (95% CI 0.68-3.19); for number of withdrawals due to adverse events, OR 1.10 (95% CI 0.68-1.75); for total number of patients experiencing adverse events, OR 0.94 (95% CI 0.78-1.14); for number of patients experiencing serious adverse events, OR 1.31 (95% CI 0.87-1.97); and for sexual dysfunction, OR 0.83 (95% CI 0.64-1.08).
CONCLUSION
There is insufficient evidence to suggest that either finasteride or dutasteride offers an advantage in efficacy or safety over the other, in terms of clinically important outcomes.
PubMed: 28487578
DOI: 10.4212/cjhp.v70i2.1643 -
BMC Musculoskeletal Disorders May 2018Dutasteride is a potent inhibitor of 5-alpha reductase enzymes that reduces concentrations of dihydrotestosterone to a greater extent than finasteride. Whether this has...
BACKGROUND
Dutasteride is a potent inhibitor of 5-alpha reductase enzymes that reduces concentrations of dihydrotestosterone to a greater extent than finasteride. Whether this has adverse implications for bone health is unknown. We compared the risk of osteoporosis and fractures in older men treated with dutasteride or finasteride.
METHODS
We conducted a population-based retrospective cohort study with high-dimensional propensity score matching of Ontario men aged 66 years or older who started treatment with dutasteride or finasteride between January 1, 2006 and December 31, 2012. The primary outcome was a diagnosis of osteoporosis within 2 years of treatment initiation. A secondary outcome was osteoporotic or fragility fractures.
RESULTS
We studied 31,615 men treated with dutasteride and an equal number of men treated with finasteride. Dutasteride-treated patients had a lower incidence of osteoporosis than those receiving finasteride [2.2 versus 2.6 per 100 person years; hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.72 to 0.93]. This effect was no longer statistically significant following adjustment for specialty of prescribing physician (HR 0.90; 95% CI 0.78 to 1.02)]. There was no differential risk of fractures with dutasteride (HR 1.04; 95% 0.86 to 1.25).
CONCLUSIONS
Despite differential effects on 5-alpha reductase, dutasteride is not associated with an increased risk of osteoporosis or fractures in older men relative to finasteride. These findings suggest that dutasteride does not adversely affect bone health.
Topics: 5-alpha Reductase Inhibitors; Aged; Aged, 80 and over; Dutasteride; Finasteride; Follow-Up Studies; Humans; Male; Ontario; Osteoporosis; Osteoporotic Fractures; Population Surveillance; Retrospective Studies; Risk Factors
PubMed: 29789004
DOI: 10.1186/s12891-018-2076-9 -
BMC Medicine Sep 2011With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite...
With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research.
Topics: 5-alpha Reductase Inhibitors; Azasteroids; Chemoprevention; Drug Approval; Dutasteride; Finasteride; Humans; Male; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 21920036
DOI: 10.1186/1741-7015-9-105 -
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 -
Clinical Interventions in Aging 2009Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and... (Review)
Review
Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and epithelial prostatic elements that surround the urethra cause lower urinary tract symptoms (LUTS), urinary tract infection and acute urinary retention. Medical treatments of symptomatic BPH include; 1) the 5alpha-reductase inhibitors, 2) the alpha1-adrenergic antagonists, and 3) the combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist. Selective alpha1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility. Clinical trials have shown that alpha1-adrenergic antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Inhibitors of 5alpha-reductase decrease production of dihydrotestosterone within the prostate resulting in decreased prostate volumes, increased peak urinary flow rates, improvement of symptoms, and decreased risk of acute urinary retention and need for surgical intervention. Interim results of the ongoing Combination of Avodart and Tamsulosin (CombAt) study have shown combination therapy with the 5alpha-reductase inhibitor dutasteride and the alpha1-adrenergic antagonist tamsulosin offer significant improvements from baseline compared with either drug alone.
Topics: Aged; Antineoplastic Agents; Azasteroids; Cholestenone 5 alpha-Reductase; Drug Therapy, Combination; Dutasteride; Enzyme Inhibitors; Humans; Male; Middle Aged; Prostatic Hyperplasia; Quality of Life; Sulfonamides; Tamsulosin
PubMed: 19554096
DOI: 10.2147/cia.s4102 -
Biomedicine & Pharmacotherapy =... Nov 2021Recent literature connects 5-alpha reductase inhibitors (5-ARIs) with neuropsychiatric adverse effects. Several clinical studies have indicated that former 5-ARIs users... (Review)
Review
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.
Topics: 5-alpha Reductase Inhibitors; Administration, Oral; Adult; Affect; Aged; Animals; Brain; Depression; Dopaminergic Neurons; Female; Humans; Male; Middle Aged; Neurogenesis; Neuroinflammatory Diseases; Neurosteroids; Risk Assessment; Risk Factors; Time Factors
PubMed: 34479019
DOI: 10.1016/j.biopha.2021.112100