Suicidal risk associated with finasteride versus dutasteride among men treated for benign prostatic hyperplasia: nationwide cohort study.

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.

Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide.

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.

Efficacy and safety of dutasteride with tadalafil add-on therapy in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia.

OBJECTIVE: To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil in Japanese men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with dutasteride. RESULTS: Twenty-four patients were enrolled. The participants had a median age of 71.0 (64.8-73.0) years and a median prostate volume of 37.3 (29.7-41.8) mL as measured using transabdominal sonography. The efficacy indicators, such as International Prostate Symptom Score (IPSS), quality of life (QOL) score, night-time urinary frequency, and night-time maximum voided volume, improved significantly at 4 weeks, and the effects lasted until 24 weeks (IPSS: 9.5 vs. 17.0, QOL: 2.0 vs. 4.0, nocturia: 2.0 vs. 2.0, night-time maximum voided volume: 290.0 vs. 240.0 mL). Overactive bladder symptom score (OABSS) and sexual health inventory for men (SHIM) significantly improved at 12 weeks, and the effects lasted until 24 weeks (OABSS: 3.0 vs. 5.0, SHIM: 11.0 vs. 7.5). However, maximum urine flow and residual urine volume showed no improvement at any point. Adverse events occurred in two cases. Taken together, add-on therapy with tadalafil was effective for patients with LUTS/BPH resistant to dutasteride monotherapy. In addition, this therapy was not associated with severe adverse events.

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.

Triple Therapy with Tamsulosin, Dutasteride, and Imidafenacin for Benign Prostatic Hyperplasia in Patients with Overactive Bladder Symptoms Refractory to Tamsulosin: Subgroup Analyses of the DIrecT Study.

AIM: To verify if the efficacy of the triple therapy with tamsulosin, dutasteride, and imidafenacin (TDI) is influenced by any background characteristics in patients with overactive bladder (OAB). METHODS: A subanalysis of data from the DIrecT study was conducted. Superiority of TDI over tamsulosin and dutasteride in terms of efficacy based on the Overactive Bladder Symptom Score (OABSS), total International Prostate Symptom Score (IPSS), IPSS quality of life index, and postvoid residual (PVR) was evaluated in binary subgroups. RESULTS: In the treatment groups, there was a significant interaction of total OABSS with testosterone level (≥4.8 vs. <4.8 ng/mL, p = 0.043) and PVR (≥20 vs. <20 mL, p = 0.018). For the total IPSS, no significant interaction was found except for the IPSS QOL index. For the IPSS QOL index, a significant interaction was found with testosterone level (≥4.8 vs. <4.8 ng/mL, p < 0.0001) as well as with total IPSS and total OABSS. For the PVR, no significant interaction was found except with total OABSS. CONCLUSIONS: Triple therapy with TDI is suggested to be a therapeutic option for benign prostatic hyperplasia in patients with residual OAB symptoms refractory to tamsulosin and in patients with various background characteristics regardless of severity of OAB symptoms. Trial Registry No. UMIN 000011980.

An evaluation of the federal adverse events reporting system data on adverse effects of 5-alpha reductase inhibitors.

OBJECTIVE: To investigate the sexual, physical, and mental adverse effects associated with exposure to 5-alpha reductase inhibitors (5ARIs). METHODS: FAERS data containing finasteride and dutasteride reports were analyzed from January 2000 to April 2019. Reports identified one or more adverse effects, along with all concurrent medications. Cases of monotherapy of finasteride or dutasteride were identified. We conducted a chi-square test of independence to assess the relationship between the three drug groups and adverse event (AE) occurrence across 19 sexual, physical, and mental AE categories. The frequency procedure in SAS was utilized to summarize rates of AEs between various dosages of each drug. RESULTS: A total of 16,014 case reports were obtained. After excluding females, 7436 case reports of 5ARI monotherapy were identified: 2628 of dutasteride 0.5 mg, 3266 of finasteride 1 mg, and 744 of finasteride 5 mg. Differences in rates of AEs occurrence were statistically significant across all 19 variables (p < 0.001) with a significantly higher proportion of AEs attributed to finasteride 1 mg, with gynecomastia being the only exception. Case report submissions rose dramatically following FDA-mandated finasteride label change. CONCLUSIONS: Analysis of FAERS data suggests AEs of 5ARIs are dose-independent with greater likelihood of occurrence in younger patients, particularly in sexual and mental domains. The causality and the rate of AEs are not certain based on the FAERS data and future prospective studies are necessary to determine the true rates.

Association Between 5-Alpha Reductase Inhibitor Use and The Risk of Depression: A Meta-Analysis.

PURPOSE: To explore the association between 5α-reductase inhibitors (5ARIs) use and risk of depression based on published literature through a meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was conducted by searching Pubmed, Embase, Cochrane Library, CBM, CNKI, and VIP databases up to June, 2019. Summarized risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of association between 5ARIs and depression. Subgroup analyses were performed according to population, 5ARI types, degree of depression, and publication date. Registered in PROSPERO under number CRD42018096147. RESULTS: A total of 6 clinical studies with 265672 participants were included in our meta-analysis. The application of 5ARIs could significantly increase the risk of depression based on both pooled unadjusted (95% CI: 1.28-2.78, RR = 1.89, P = .001) and multivariable adjusted RRs (95% CI: 1.01-1.17, RR = 1.09, P = .03). In subgroup analyses, dutasteride was associated with depression significantly (95% CI: 1.37-1.70, RR = 1.53, P < .001), while finasteride was not. As to the degree of depression, 5ARIs mainly caused mild depression (95% CI: 1.91-2.33, RR = 2.11, P < .001), instead of moderate or severe depression. CONCLUSION: We concluded that 5ARIs could potentially increase the risk of depression. Clinicians need to carefully consider the use of 5ARIs for benign prostatic hyperplasia and androgenic alopecia patients, especially those exhibiting risk factors for depression or those who have a previous history of depression. More studies with larger sample size and comprehensive study design are needed to further verify our outcomes.

Co-administration of 5α-reductase Inhibitors Worsens the Adverse Metabolic Effects of Prescribed Glucocorticoids.

CONTEXT: Glucocorticoids (GCs) are commonly prescribed, but their use is associated with adverse metabolic effects. 5α-reductase inhibitors (5α-RI) are also frequently prescribed, mainly to inhibit testosterone conversion to dihydrotestosterone. However, they also prevent the inactivation of GCs. OBJECTIVE: We hypothesized that 5α-RI may worsen the adverse effects of GCs. DESIGN: Prospective, randomized study. PATIENTS: A total of 19 healthy male volunteers (age 45 ±â€…2 years; body mass index 27.1 ±â€…0.7kg/m2). INTERVENTIONS: Participants underwent metabolic assessments; 2-step hyperinsulinemic, euglycemic clamp incorporating stable isotopes, adipose tissue microdialysis, and biopsy. Participants were then randomized to either prednisolone (10 mg daily) or prednisolone (10 mg daily) plus a 5α-RI (finasteride 5 mg daily or dutasteride 0.5 mg daily) for 7 days; metabolic assessments were then repeated. MAIN OUTCOME MEASURES: Ra glucose, glucose utilization (M-value), glucose oxidation, and nonesterified fatty acids (NEFA) levels. RESULTS: Co-administration of prednisolone with a 5α-RI increased circulating prednisolone levels (482 ±â€…96 vs 761 ±â€…57 nmol/L, P = 0.029). Prednisolone alone did not alter Ra glucose (2.55 ±â€…0.34 vs 2.62 ±â€…0.19 mg/kg/minute, P = 0.86), M-value (3.2 ±â€…0.5 vs 2.7 ±â€…0.7 mg/kg/minute, P = 0.37), or glucose oxidation (0.042 ±â€…0.007 vs 0.040 ±â€…0.004 mmol/hr/kg/minute, P = 0.79). However, co-administration with a 5α-RI increased Ra glucose (2.67 ±â€…0.16 vs 3.05 ±â€…0.18 mg/kg/minute, P < 0.05) and decreased M-value (4.0 ±â€…0.5 vs 2.6 ±â€…0.4 mg/kg/minute, P < 0.05), and oxidation (0.043 ±â€…0.003 vs 0.036 ±â€…0.002 mmol/hr/kg, P < 0.01). Similarly, prednisolone did not impair insulin-mediated suppression of circulating NEFA (43.1 ±â€…28.9 vs 36.8 ±â€…14.3 µmol/L, P = 0.81), unless co-administered with a 5α-RI (49.8 ±â€…8.6 vs 88.5 ±â€…13.5 µmol/L, P < 0.01). CONCLUSIONS: We have demonstrated that 5α-RIs exacerbate the adverse effects of prednisolone. This study has significant translational implications, including the need to consider GC dose adjustments, but also the necessity for increased vigilance for the development of adverse effects.

Cerebral Venous Sinus Thrombosis Associated with Dutasteride Use.

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults with known risk factors of prothrombotic conditions, pregnancy, infection, malignancy, and drugs. Dutasteride is a 5α-reductase inhibitor that is used for benign prostate hypertrophy and androgenetic alopecia. To date, CVT caused by dutasteride use has not been reported. A 25-year-old male presented with headache and diplopia. He had taken 0.5 mg of dutasteride every other day for 9 months to treat alopecia. A headache developed 7 months after he started taking medication, and horizontal diplopia occurred 1 month after the onset of headache. Fundus examination showed bilateral papilledema. Brain magnetic resonance imaging showed thrombosis in the left sigmoid and transverse sinuses. Headache and diplopia improved after discontinuing dutasteride and starting anticoagulation. The results from this case report indicated dutasteride as a potential cause of CVT. Presumably, the increased estrogen level due to dutasteride use caused the formation of a thrombus.

Lack of Association between 5α-Reductase Inhibitors and Depression.

PURPOSE: Depressed mood and suicidality reported with 5α-reductase inhibitors (finasteride and dutasteride) during post-marketing surveillance resulted in the addition of depression risk to finasteride labeling. As peer reviewed studies are limited and have reported mixed findings, we further evaluated 5α-reductase inhibitor exposure and depression risk using sequence symmetry analysis. MATERIALS AND METHODS: National Veterans Health Administration administrative data were used to identify 53,848 male patients initiating 5α-reductase inhibitor therapy during fiscal year 2014. Incident depression events were assessed separately using the 2 measures of antidepressant prescription and depression diagnosis. Symmetry ratios were calculated as the ratio of patients with an incident depression event in the year following 5α-reductase inhibitor initiation to the year preceding initiation. An identical exposure counterfactual analysis was conducted among veterans initiating α1-adrenergic receptor antagonists. RESULTS: Incident antidepressant prescribing was observed in 2,563 patients following 5α-reductase inhibitor initiation and 3,051 patients preceding 5α-reductase inhibitor initiation (SR 0.84, 95% CI 0.80-0.89). Similar findings were observed for incident depression diagnosis (SR 0.83, 95% CI 0.79-0.86). Stratification by age group, 5α-reductase inhibitor agent, antidepressant class, prior α1-adrenergic receptor antagonist exposure and depression diagnosis type failed to demonstrate any positive association between 5α-reductase inhibitor and depression. Nearly identical results were observed in the α1-adrenergic receptor antagonist analysis (SR 0.87, 95% CI 0.84-0.90). CONCLUSIONS: Initiation of a 5α-reductase inhibitor was not associated with increased risk of depression. Our findings support the hypothesis that depression is more likely attributable to underlying benign prostatic hyperplasia and associated lower urinary tract symptoms than 5α-reductase inhibitor exposure.

Men's Sexual Health Questionnaire score changes vs spontaneous sexual adverse event reporting in men treated with dutasteride/tamsulosin combination therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia: A post hoc analysis of a prospective, randomised, placebo-controlled study.

AIM: To assess the impact of baseline characteristics on Men's Sexual Health Questionnaire (MSHQ) total scores and to evaluate the clinical relevance of MSHQ changes and their association with spontaneously reported sexual adverse events (SexAEs) in patients with benign prostatic hyperplasia. METHODS: This was a post hoc analysis of the Phase 4 FDC116115 study, in which patients aged ≥50 years were randomised 1:1 to receive a fixed-dose combination of dutasteride 0.5 mg and tamsulosin 0.4 mg (DUT-TAM FDC), or placebo. End-points included: change in MSHQ total scores by baseline characteristics and SexAEs; cumulative distribution function for change from baseline to month 12 in MSHQ total score and the ejaculation, erection, satisfaction and sexual desire (libido) domain scores; and relationship between changes in MSHQ scores and SexAEs. RESULTS: The intent-to-treat population comprised 489 patients (DUT-TAM FDC, n = 243; placebo, n = 246). The mean reduction in total MSHQ score was greater in patients with SexAEs across both groups, compared with patients without SexAEs. Most patients reporting any SexAE (86% DUT-TAM FDC, 67% placebo) had a worsening of the MSHQ total score at month 12 compared with baseline. Specifically, 90% (DUT-TAM FDC) and 75% (placebo) of patients reporting an ejaculation SexAE and 73% (DUT-TAM FDC) and 87% (placebo) of patients reporting an erection SexAE had a worsening of MSHQ ejaculation and erection domain scores, respectively, at month 12. A threshold effect for incident SexAE was observed; patients showing a decrease of approximately 6-10 points in the total MSHQ score were more likely to report SexAEs. CONCLUSION: Findings support the clinical utility of the MSHQ tool in assessing the impact of DUT-TAM on sexual function by linking numerical changes in MSHQ scores to spontaneously reported SexAEs for the first time. The threshold effect for incidence of SexAEs warrants further investigation to determine its clinical relevance.

Effectiveness and safety of oral dutasteride for male androgenetic alopecia in real clinical practice: A descriptive monocentric study.

The objective of our study was to describe the effectiveness and safety of oral dutasteride (OD) for male androgenetic alopecia in real clinical practice. A retrospective, monocentric, and descriptive study was designed. Male patients with androgenetic alopecia that had received OD for at least 12 months were included. Three or less capsules of 0.5 mg per week were considered low doses. Therapeutic response was assessed by comparison of pre- and post-treatment (at month 12) clinical images by three independent dermatologists with expertise in hair disorders, using a four-point scale (worsening, stabilization, mild improvement or marked improvement). In all, 307 patients with a mean age of 35.3 years (range 18-79) were included. Eight patients (2.6%) required the discontinuation of the drug due to decreased libido (n = 4), gynecomastia (n = 2), mood disorder (n = 1) and erectile dysfunction (n = 1). All these AE resolved after stopping the medication. No AE were detected in patients receiving low doses of OD. The effectiveness was evaluated in the subgroup of 42 patients (13.7%) who received OD in monotherapy: 38 patients improved (90%), 10 of them (23.8%) presenting a marked improvement, 4 patients (9.5%) were stable and none patient worsened. In conclusion, OD is an effective treatment for male androgenetic alopecia in real clinical practice, presenting a good safety profile, especially at lower doses.

Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study.

OBJECTIVE: To investigate the incidence of new onset type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors (dutasteride or finasteride) for long term treatment of benign prostatic hyperplasia. DESIGN: Population based cohort study. SETTING: UK Clinical Practice Research Datalink (CPRD; 2003-14) and Taiwanese National Health Insurance Research Database (NHIRD; 2002-12). PARTICIPANTS: Men in the CPRD who received dutasteride (n=8231), finasteride (n=30 774), or tamsulosin (n=16 270) were evaluated. Propensity score matching (2:1; dutasteride to finasteride or tamsulosin) produced cohorts of 2090, 3445, and 4018, respectively. In the NHIRD, initial numbers were 1251 (dutasteride), 4194 (finasteride), and 86 263 (tamsulosin), reducing to 1251, 2445, and 2502, respectively, after propensity score matching. MAIN OUTCOMES MEASURE: Incident type 2 diabetes using a Cox proportional hazard model. RESULTS: In the CPRD, 2081 new onset type 2 diabetes events (368 dutasteride, 1207 finasteride, and 506 tamsulosin) were recorded during a mean follow-up time of 5.2 years (SD 3.1 years). The event rate per 10 000 person years was 76.2 (95% confidence interval 68.4 to 84.0) for dutasteride, 76.6 (72.3 to 80.9) for finasteride, and 60.3 (55.1 to 65.5) for tamsulosin. There was a modest increased risk of type 2 diabetes for dutasteride (adjusted hazard ratio 1.32, 95% confidence interval 1.08 to 1.61) and finasteride (1.26, 1.10 to 1.45) compared with tamsulosin. Results for the NHIRD were consistent with the findings for the CPRD (adjusted hazard ratio 1.34, 95% confidence interval 1.17 to 1.54 for dutasteride, and 1.49, 1.38 to 1.61 for finasteride compared with tamsulosin). Propensity score matched analyses showed similar results. CONCLUSIONS: The risk of developing new onset type 2 diabetes appears to be higher in men with benign prostatic hyperplasia exposed to 5α-reductase inhibitors than in men receiving tamsulosin, but did not differ between men receiving dutasteride and those receiving finasteride. Additional monitoring might be required for men starting these drugs, particularly in those with other risk factors for type 2 diabetes.

Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia.

BACKGROUND: We performed a meta-analysis to confirm the efficacy and safety of the combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia (BPH) during a treatment cycle of at least 1 year. METHODS: Randomized controlled trials were searched by using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The data was evaluated and statistically analyzed by using RevMan version 5.3.0. RESULTS: Five studies including 4348 patients were studied. The analysis found that the combination group was significantly greater effect in international prostate symptom score (mean difference [MD], - 1.43; 95% confidence interval [CI], - 2.20 to - 0.66; P = 0.0003), prostate volume (MD, - 10.13; 95% CI, - 12.38 to - 7.88; P < 0.00001), transitional zone volume (MD, - 3.18; 95% CI, - 3.57 to - 2.79; P<0.0001), maximum urine flow rate (MD, 1.05; 95% CI, 0.82 to 1.29; P < 0.00001), prostate specific antigen (MD, - 0.54; 95% CI, - 0.80 to - 0.29; P < 0.0001) and post-void residual volume (MD, - 3.85; 95% CI, - 4.95 to - 2.76; P < 0.00001) compared with the tamsulosin group. In terms of safety, including adverse events (odds ratio [OR], 2.06; 95% CI, 1.34 to 3.17; P = 0.001), erectile dysfunction (OR, 2.24; 95% CI, 1.73 to 2.92; P < 0.00001), ejaculation disorder (OR, 3.37; 95% CI, 1.97 to 5.79; P < 0.0001), retrograde ejaculation (OR, 2.30; 95% CI, 1.08 to 4.93; P = 0.03), decreased libido (OR, 2.25; 95% CI, 1.53 to 3.31; P < 0.0001) and loss of libido (OR, 3.38; 95% CI, 1.94 to 5.88; P<0.0001), the combination group showed poor tolerance than the tamsulosin group with the exception of dizziness (OR, 1.16; 95% CI, 0.75 to 1.80; P = 0.50). The combination group significantly reduced the risk of clinical progression than the tamsulosin group especially in incidence of BPH-related symptom progression (OR, 0.56; 95% CI, 0.46 to 0.67; P < 0.00001) and acute urinary retention (OR, 0.61; 95% CI, 0.38 to 0.98; P = 0.04). CONCLUSION: The combination of tamsulosin plus dutasteride provides a preferable therapeutic effect for BPH with a higher incidence of sexual side effects, but combination-therapy can markedly reduce risk of BPH-related symptom progression and acute urinary retention relative to tamsulosin monotherapy.

A 52-week multicenter randomized controlled study of the efficacy and safety of add-on dutasteride and imidafenacin to tamsulosin in patients with benign prostatic hyperplasia with remaining overactive bladder symptoms (DIrecT study).

OBJECTIVE: The aim of this study was to examine the long-term efficacy of combination of tamsulosin 0.2 mg + dutasteride 0.5 mg + imidafenacin 0.2 mg (TDI) therapy compared with tamsulosin + dutasteride (TD) therapy for 52 weeks in benign prostatic hyperplasia (BPH) patients with a prostate volume (PV) ≥30 mL and remaining overactive bladder (OAB) symptoms after having received tamsulosin for ≥8 weeks. Previously, we reported that the improvement in OAB symptoms at 24 weeks was significantly greater in the TDI than TD group. METHODS: BPH patients with OAB symptoms after ≥8 weeks tamsulosin were randomly assigned to the TDI or TD group in a ratio of 1:1 ratio, and followed-up for 52 weeks. Changes in the OAB Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and post-void residual (PVR) were evaluated. RESULTS: In all, 163 patients were randomized, and 125 patients (76.7%) completed 52 weeks of treatment. At Week 52, there were significant decreases in the OABSS and IPSS storage subscore compared with baseline in the TDI versus TD group, but the change in the total IPSS did not differ significantly between the two groups. There was no change in PVR from Week 24 to Week 52 in either group. CONCLUSIONS: For BPH patients with PVR ≥30 mL and remaining storage symptoms despite tamsulosin monotherapy, TDI treatment showed better results in terms of improved OAB symptoms than TD treatment up to 52 weeks.

Why Odds Ratios Can Be Tricky Statistics: The Case of Finasteride, Dutasteride, and Sexual Dysfunction.

Finasteride and dutasteride are 5α-reductase inhibitor drugs that are used to treat benign prostatic hyperplasia (BPH). Randomized controlled trials (RCTs) conducted in men with BPH show that these drugs impair libido and cause erectile dysfunction. Meta-analyses of the RCTs confirm the findings, estimating odds ratio (OR) values for these adverse effects at around 1.50. A problem with meta-analyses that do not report absolute risks with drug vs placebo and that extract ORs instead of relative risks (RRs) from RCT data is that it is hard for the reader to know how to interpret the findings and communicate them to patients. Had the RR been 1.50, the reader would conclude that the risk with drug is 50% higher than the risk with placebo; this is easily understood because the risk with placebo would be available from the RCTs. In contrast, an OR of 1.50 means that the odds with drug are 50% higher than the odds with placebo; understanding this requires a knowledge of what the odds with placebo are as well as an understanding of what odds mean. Odds are not as easily understood as risks are. Odds are numerically different from risks, and the OR is numerically different from the RR. The difference between the OR and the RR is numerically small when the risks are similar in the two groups and also when the risks are dissimilar but the risk is small in the group of interest. The difference between the OR and the RR becomes increasingly large when the risks are dissimilar in the two groups and when the risk in the group of interest is not small. Smallness of risk, in this context, has been conservatively stated as 10%, but it could be possible to use a higher cutoff, such as 20%. Other issues related to risk, odds, RR, and OR are also discussed.

The Risk of Sexual Dysfunction and Effectiveness of Treatment of Benign Prostatic Hyperplasia With Severe Lower Urinary Tract Dysfunction With Combination of Dutasteride and Solifenacin.

INTRODUCTION: Correction of benign prostatic hyperplasia (BPH) with lower urinary tract (LUT) symptoms (LUTS) is treated with drugs of different pharmacological classes having side effects including suppression of sexual function. AIM: To assess the effect of simultaneous intake of dutasteride and solifenacin on the reversibility of severe LUTS and sexual function in men with BPH. METHODS: Patients from group A took dutasteride 0.5 mg/d, those from group В took dutasteride 0.5 mg/d and solifenacin 10 mg/d, and those from group С took dutasteride 0.5 mg/d and solifenacin 20 mg/d. The duration of the observation was 6 months. The sexual function was rated with the International Index of Erectile Function questionnaire and Men's Sexual Health Questionnaire-ejaculatory dysfunction. The functional status of LUT was rated with International Prostate Symptom Score, overactive bladder questionnaire-awareness tool, diary voiding, and uroflowmetry. MAIN OUTCOME MEASURE: The state of sexual function and function of the LUT in men improved. RESULTS: The erectile function in all men, having participated in the study, did not change [group A, 9.8 (1.6)/9.4 (3.8), P ≥ .05; group B, 10.1 (2.1)/10.5 (3.7), P ≥ .05; group C, 9.7 (1.5)/9.5 (2.6), P ≥ .05]. The ejaculator function significantly decreased in all groups. According to International Prostate Symptom Score, obstruction diminished in this group [incomplete emptying, 3.7 (0.7)/1.5 (0.3), P ≤ .05; intermittence, 3.5 (1.0)/3.5 (1.0), P ≤ .05; weak stream, 3.8 (0.6)/1.5 (0.4), P ≤ .05; straining, 3.4 (0.5)/0.7 (0.7), P ≤ .05] as did hyperactivity [urgency, 2.8 (0.7)/0.9 (0.7), P ≤ .05; nocturia, 2.8 (0.6)/1.2 (0.4), P ≤ .05]. All numbers in the manuscript are given in points unless otherwise stated. The values in parentheses are SD (unless otherwise specified). CLINICAL IMPLICATIONS: The information that a high dose of solifenacin administered concomitantly with dutasteride may contribute to increase in sexual satisfaction and preservation of erectile function at the baseline level can be useful and used by sexologists, urologists, and family doctors. STRENGTH & LIMITATIONS: The combination of dutasteride 0.5 mg/d and solifenacin 10 mg/d saves erectile function and improves sexual satisfaction. At the same time, the symptoms of obstruction and hyperactivity disappear or are reduced in most patients. Nevertheless, we did not study late results of the combined therapy. CONCLUSION: Suggested combination does not impact on erectile function but decreases ejaculator function; however, it does not affect a general high rating of sexual function by patients. Thus, overall sexual function in men with BPH and severe LUTS is not impaired by prolonged intake of double dosage of solifenacin combined with dutasteride. The combination of dutasteride and solifenacin is effective and safe to treat BPH and severe LUTS. Kosilov K, Kuzina I, Kuznetsov V, et al. The Risk of Sexual Dysfunction and Effectiveness of Treatment of Benign Prostatic Hyperplasia With Severe Lower Urinary Tract Dysfunction With Combination of Dutasteride and Solifenacin. J Sex Med 2018;15:1579-1590.

Superiority of dutasteride 0.5 mg and tamsulosin 0.2 mg for the treatment of moderate-to-severe benign prostatic hyperplasia in Asian men.

OBJECTIVES: To assess the effectiveness and safety of dutasteride 0.5 mg + tamsulosin 0.2 mg combination compared with tamsulosin 0.2 mg in Asian men with moderate-to-severe benign prostatic hyperplasia. METHODS: A 4-week, single-blind, placebo, run-in was followed by a 2-year double-blind randomized controlled trial in men age ≥50 years with symptomatic benign prostatic hyperplasia, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate-specific antigen ≥1.5 and ≤10 ng/mL, peak urinary flow >5 and ≤15 mL/s, and voided volume of ≥125 mL. Participants were randomized to oral daily dutasteride 0.5 mg + tamsulosin 0.2 mg combination or tamsulosin 0.2 mg. The primary efficacy end-point was change in International Prostate Symptom Score at year 2. RESULTS: Data from 607 participants showed a significant reduction in International Prostate Symptom Score (P < 0.05) at month 24, along with greater improvements (P ≤ 0.006) in peak urinary flow at every assessment and significant prostate volume reduction at months 12 and 24 (P < 0.001) in the combination group. Combination therapy was associated with a significant reduction in the risk of acute urinary retention or benign prostatic hyperplasia-related surgery (P = 0.012), primarily due to a significant reduction in the risk of acute urinary retention (P = 0.005). The safety and tolerability profile of combination therapy was consistent with the known profiles for the individual monotherapies. CONCLUSIONS: Dutasteride 0.5 mg + tamsulosin 0.2 mg combination therapy showed better clinical outcomes than tamsulosin 0.2 mg monotherapy, making it an effective and safe treatment option for Asian men with moderate-to-severe benign prostatic hyperplasia.