The association of 5-alpha reductase inhibitor (5ARI) therapy and sexual dysfunction has been reported. Some patients claim persistent erectile dysfunction despite long-term discontinuation of 5ARI treatment. The aim of this study was to assess erectile function after cessation of 5ARI therapy using a rat model.
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1713 patients were included for analysis. Mean (SD) IPSS and BII scores at baseline were 16.8 (5.4) and 6.8 (2.6), respectively. 8.9 % (n = 153) of study participants did not receive treatment (watchful waiting, WW), 70.3 % (n = 1204) were prescribed monotherapy (alpha-adrenergic blockers [AB]; phytotherapy [PT, of which 95.2 % was the hexanic extract of Serenoa repens, HESr]; or 5-alpha-reductase inhibitors [5ARI]), and 20.8 % (n = 356) received combined treatment (AB + 5ARI; AB + HESr; others). At 6 months, improvements in QoL were similar across the different medical treatment (MT) groups, both for monotherapy (AB: mean improvement [SD] of 2.4 points [2.4]; PT: 1.9 [2.4]; 5ARI: 2.5 [2.3]) and combined therapy (AB + 5ARI: 3.1 [2.9]; AB + PT: 3.1 [2.5]). There were no clinically significant differences between MT groups and all showed significant improvement over WW (p < 0.05). HESr showed similar efficacy to AB and 5ARI both as monotherapy and in combination with AB. Results on the IPSS were similar.
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Although dutasteride reduced serum dihydrotestosterone (DHT) by 86-89% in 2-4 weeks, and intraprostatic DHT was approximately 10 times lower than in the placebo group, the (adjusted) mean haemoglobin (Hb) loss during surgery was 2.15-2.55 g Hb/g resectate with no significant difference in blood loss between the groups either during or after TURP. Clot retention occurred in 6-11% and urinary incontinence in 14-15% of patients during the 14 weeks after TURP, with no difference between the groups. The MVD at TURP was also similar for all groups.
We performed a population based cohort study of Ontario men 66 years old or older who commenced treatment with dutasteride or finasteride between October 1, 2005 and March 31, 2015. For each individual treated with dutasteride, we identified 1 treated with finasteride, matching on a propensity score and calendar quarter of treatment initiation to account for temporal changes in prescribing. The primary outcome was hospitalization for heart failure. Secondary analyses were done to examine acute myocardial infarction and stroke. Cox proportional hazards regression was used to adjust for differences between groups.
This multicenter, international, double-blind, randomized study included men 50 years old or older with International Prostate Symptom Score 12 or greater, prostate volume 30 cc or greater, total prostate specific antigen 1.5 to 10.0 ng/ml, maximum urinary flow greater than 5 and less than or equal to 15 ml per second and minimum voided volume 125 ml or greater. Patients were randomized to dutasteride (0.5 mg) and/or tamsulosin (0.4 mg) but results are reported without respect to treatment. International Prostate Symptom Score and Patient Perception of Study Medication responses were assessed at baseline and at 3-month intervals for 48 months. Using pooled data Patient Perception of Study Medication responses were correlated with changes in International Prostate Symptom Score from baseline for 2 Patient Perception of Study Medication measures, including 1) total score and 2) overall satisfaction on question 11, "Overall how satisfied are you with the study medication and its effect on your urinary problems?"
Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause.
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Over the last 15 years, there has been a steady increase in the use of medications to manage men with BPH. Providers seem to have readily adopted novel medications and treatment regimens in response to FDA approval and supportive level 1 evidence.
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11,822 dutasteride users and 5,781 finasteride users were identified. Most users started treatment in combination with an alpha-blocker. Overall, dutasteride users had a lower risk of BPH-related prostate surgery was lower among dutasteride users than finasteride users (HR: 0.75; 95 % CI: 0.56-0.99). This lower risk among dutasteride users was also seen when stratifying by monotherapy or combination therapy (HR: 0.73; 95 % CI: 0.54-0.98 for monotherapy and HR: 0.85; 95 % CI: 0.74-0.97 for combination therapy). However, the association was only present among men treated by urologists. For AUR the rates were low and no statistical significant difference was observed between dutasteride and finasteride users.
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One hundred sixty consecutive patients were identified, of which 117 were not on a 5ARI and 43 were on either finasteride or dutasteride for at least 6 months. Mean prostate volumes were 72.8 +/- 49.5 cm3 and 70.8 +/- 49.1 cm3 (P = 0.39), respectively. There were no significant differences in the parameters of laser time (32.0 +/- 27.6 minutes and 37.0 +/- 36.2 minutes) and energy usage (97.4 +/- 91.6 kJ and 103.3 +/- 86.0 kJ). All were outpatient procedures with the majority of patients catheter-free at discharge. All patients were able to discontinue their prostate medications after surgery. IPSS, Qmax, and PVR values showed significant improvement within each group, but the degree of improvement between the 2 groups did not show statistical significance.
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In the present pilot study, treatment with dutasteride resulted in a significant decrease in serum PSA in men with serologic relapse following radical treatment for adenocarcinoma of the prostate. These data appear to suggest that dutasteride may delay or prevent progression of prostate cancer in some men with biochemical relapse after radical therapy. These findings require confirmation in the setting of a larger, longer trial.
Despite increased cost due to taking a drug for prevention, dutasteride 0.5 mg/day may be cost effective in men at increased risk for PCa.
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As the prevalence of both erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) increases with age, physicians could be in the position to manage these two conditions simultaneously. Moreover, medical therapies for either one of these conditions can affect the other and this should be carefully considered when making treatment decisions. Pharmacotherapy for benign prostatic hyperplasia (BPH)/LUTS can cause side-effects affecting sexual function. Hence, 5alpha-reductase inhibitors such as finasteride and dutasteride are associated with a greater risk of ED, ejaculatory disorders (EjD) and decreased libido than is placebo. Among alpha1-adrenergic blockers, tamsulosin is associated with an increased risk of EjD. However, some alpha1-adrenergic blockers can also have a positive impact on erection. This is the case for alfuzosin, which has been shown to enhance erectile function in experimental models, probably by reducing the sympathetic tone and thus relaxing corpus cavernosum smooth muscle cells. Phosphodiesterase 5 (PDE-5) inhibitors are commonly used to treat ED. There is increasing evidence that they might also have a beneficial effect on LUTS, probably through the nitric-oxide pathway. Nitric oxide is an important mediator of the relaxation of isolated bladder and urethral smooth muscle, and could modulate prostatic smooth muscle tone. Alpha1-adrenergic blockers and PDE-5 inhibitors can therefore have a positive impact on both ED and LUTS. Although placebo-controlled studies are needed to confirm the impact of these drugs, alone or combined, on both ED and LUTS, this reinforces the need for a common approach to managing these two highly prevalent and bothersome conditions.
There was a clinically meaningful improvement in AUA-SI in patients on dutasteride in the double-blind phase, but not in those on placebo. At 48 months, patients on dutasteride in both study phases had greater improvements in AUA-SI score and individual question scores than those on dutasteride in the open-label phase only. The proportion of patients with severe symptoms declined in both study groups, although these changes were more profound in those receiving dutasteride for the 4-year duration of the study.
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Recent evidence indicates that neuroactive steroids may participate in the pathogenesis of schizophrenia spectrum disorders, yet the mechanisms of this involvement are elusive. As 5-alpha-reductase (5AR) is the rate-limiting enzyme of one of the two major metabolic pathways in brain steroidogenesis, we investigated the effects of its blockade in several rat models of psychotic-like behavior. The 5AR inhibitor finasteride (FIN, 60 or 100 mg/kg, intraperitoneal, i.p.) dose- and time-dependently antagonized prepulse inhibition (PPI) deficits induced by apomorphine (APO, 0.25 mg/kg, subcutaneous, s.c.) and d-amphetamine (AMPH, 5 mg/kg, s.c.), in a manner analogous to haloperidol (HAL, 0.1 mg/kg, i.p.) and clozapine (CLO, 5 mg/kg, i.p.). Similar results were observed with the other 5AR inhibitors dutasteride (DUT, 40 or 80 mg/kg, i.p.) and SKF 105111 (30 mg/kg, i.p.). FIN (60 or 100 mg/kg, i.p.) also reduced hyperlocomotion induced by AMPH (1 or 3 mg/kg, s.c.) and attenuated stereotyped behaviors induced by APO (0.25 mg/kg, s.c.). Nevertheless, FIN (100 mg/kg, i.p.) did not reverse the PPI disruption induced by the N-methyl-d-aspartate receptor antagonist dizocilpine (0.1 mg/kg, s.c.). FIN (60-300 mg/kg, i.p.) induced no catalepsy in either the bar test or the paw test. Our results suggest that 5AR inhibitors elicit antipsychotic-like effects in animals and may be proposed as a putative novel target in the management of psychotic disorders.
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To determine whether conservative management of benign prostatic hyperplasia (BPH) is an appropriate option for patients with bladder stones.
We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated.
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The effectiveness of finasteride and dutasteride in women with androgenetic alopecia has been the subject of debate.
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A total of 2,802 men 50 years or older with a clinical diagnosis of benign prostatic hyperplasia, no history of prostate cancer, PSA 1.5 to 10 ng/ml, prostate volume 30 cc or greater, an American Urological Association symptom score of 12 or greater and peak urinary flow rate 15 ml per second or less were randomized to 0.5 mg dutasteride daily or matching placebo for 24 months. Increases in PSA from baseline and the maximum increase from nadir to month 24 were compared between the groups and analyzed by prostate cancer status, as determined by PSA driven biopsy and an advised cutoff of more than 4 ng/ml after doubling to correct for dutasteride treatment with sensitivity and specificity calculated for each.
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Direct-to-consumer advertising (DTCA) remains a controversial issue, with concerns that it leads to unnecessary and inappropriate prescribing. Whether DTCA shifts prescribing from first-line (guideline-recommended) therapy to second-line drugs has not been studied.
Five randomized controlled trials (RCTs) and 5 retrospective cohort studies involving 1,022 patients with benign prostate hyperplasia were analyzed based on the inclusion criteria. Pooled analysis revealed that preoperative treatment with dutasteride had a significantly smaller decrease in hemoglobin (weighted mean difference [WMD] -0.47, 95% CI -0.70 to -0.24, p < 0.0001) and hematocrit levels (WMD -1.03, 95% CI -1.73 to -0.33, p = 0.004); However, no signiﬁcant difference has been found in terms of the total blood loss during TURP and blood loos per gram of resected prostatic tissue, the weight of resected prostate tissue, the microvessel density of the prostate, and the transfusion rate between the dutasteride and the control group.
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Area under the receiver operating characteristic curves (AUC) were used to compare different models with different predictors. Net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess changes in risk prediction by adding genetic markers.
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Both normal and pathological growth of the prostate is dependent on dihydrotestosterone (DHT) synthesis, which is catalysed by two 5alpha-reductase (5alphaR) isoenzymes, 5alphaR1 and 5alphaR2, of which only 5alphaR2 has traditionally been viewed as important in the prostate. The objective of this study was to evaluate the role of both isoenzymes during development/progression of prostate cancer.