Search

Objective: To evaluate the efficacy and safety of simultaneous administration of dutasteride, tadalafil and solifenacin in the treatment of benign prostatic hyperplasia (BPH) with overactive bladder symptoms and lower urinary tract obstruction in previously unsuccessfully treated men. Methods: Patients in Group A (n=97) received dutasteride 0.5 mg/day, tadalafil 2.5 mg/day, and solifenacin 2.5 mg/day; Group B (n=95) received dutasteride 0.5 mg/day, tadalafil 5 mg/day, and solifenacin 5 mg/day; Group C (n=103) received dutasteride 0.5 mg/day, tadalafil 20 mg/day, and solifenacin 10 mg/day. The functional status of the lower urinary tract was assessed using the International Prostate Symptom Score (I-PSS), Overactive Bladder Questionnaire (OABq), International Index of Erectile Function (IIEF), and Male Sexual Health Questionnaire Ejaculatory Dysfunction (MSHQ-EjD) as well as uroflowmetry. Results: The total score of the sexual function remained unchanged in Group B of patients 81.3 points vs. 80.2 points (p>0.05) according to MSHQ-EjD, 61.4 points vs. 51.2 points (p>0.05) according to IIEF data. The total assessment of symptoms of hyperactivity significantly decreased in Group C according to OABq data after the 4th week of the study (17.5 points vs. 26.1 points, p

PURPOSE To identify the clinical factors resulting in the failure of dutasteride add-on treatment to alpha-adrenergic antagonist for patients with lower urinary tract symptoms and benign prostatic enlargement (BPE). METHODS We retrospectively surveyed the patient cohort who had been enrolled in the study of dutasteride add-on treatment to alpha-adrenergic antagonist from December 2009 to November 2011. Treatment failure was defined as receiving surgery for BPE or requiring intermittent catheterization or permanent bladder catheter for urinary retention or huge postvoid residual urine. Clinical parameters before dutasteride treatment were compared between the successful and failed group. RESULTS Of 92 patients, 23 (25%) were defined as treatment failure at 7-109 months (mean: 38 months) after dutasteride add-on treatment. In the failed group, the patient' age was younger (71.6 ± 6.8 vs 75.4 ± 8.4, p = 0.033), prostatic volume (PV) was larger (76 ± 41 vs 49 ± 26 ml, p = 0.005), voiding efficiency was lower (54 ± 27 vs 68 ± 24%, p = 0.045) and bladder outlet obstruction index was higher (73 ± 30 vs 48 ± 30, p = 0.015). The cox proportional-hazards model indicated that only intravesical prostatic protrusion (IPP) was associated with treatment failure. Non-failure rate at 3 years after dutasteride add-on treatment was 89% with patients of IPP

A TLC densitometric method was developed and validated for simultaneous determination of dutasteride and tamsulosin in their challenging combined pharmaceutical formulation, where the separation process was achieved using a mobile phase composed of ethyl acetate: methanol: hexane: ammonia (90: 5: 3: 2 by volume) on pre-coated silica gel (60 GF254) plates, densitometric quantification was performed at 270 nm for both drugs. TAMS and DUTA were resolved with Rf values of 0.57± 0.01 and 0.72 ± 0.01 with a mean percentage recovery of 100.51 ± 0.659 and 100.81 ± 0.743, respectively. Method validation was performed following the International Conference on Harmonization (ICH) guidelines and was victoriously applied for simultaneous determination of tamsulosin HCl and dutasteride in their pharmaceutical formulation. The acquired results of the Proposed method were statistically compared with those acquired by the reported methods, demonstrating no significant difference. Therefore, the proposed method has the potential for being fast, simple, economic, and selective for sustainable analysis of the cited drugs.

In men, complaints of nocturia causing poor sleep are often attributed to benign prostatic hyperplasia and treated with benign prostatic hyperplasia medications. We assessed whether treating lower urinary tract symptoms with dutasteride altered either nocturia or sleep quality using data from REDUCE.REDUCE was a 4-year randomized, multicenter trial comparing dutasteride 0.5 mg/day vs placebo for prostate cancer chemoprevention. Study participants were men considered at increased risk for prostate cancer. Eligibility included age 50-75 years, prostate specific antigen 2.5-10 ng/ml, and 1 negative prostate biopsy. At baseline, 2 years and 4 years, men completed the International Prostate Symptom Score and Medical Outcomes Study Sleep Scale, a 6-item scale assessing sleep. To test differences in nocturia and Medical Outcomes Study Sleep Scale over time, we used linear mixed models adjusted for baseline confounders. Subanalyses were conducted in men symptomatic from lower urinary tract symptoms, nocturia, poor sleep, or combinations thereof.Of 6,914 men with complete baseline data, 80% and 59% were assessed at 2 and 4-year followup, respectively. Baseline characteristics were balanced between treatment arms. Dutasteride improved nocturia at 2 (-0.15, 95% CI -0.21, -0.09) and 4 years (-0.24, 95% CI -0.31, -0.18) but did not improve sleep. When limited to men symptomatic from lower urinary tract symptoms, nocturia, poor sleep or combinations thereof, results mirrored findings from the full cohort.In men with poor sleep who complain of nocturia, treatment of lower urinary tract symptoms with dutasteride modestly improves nocturia but has no effect on sleep. These results suggest men with poor sleep who complain of nocturia may not benefit from oral benign prostatic hyperplasia treatment.

To prospectively evaluate the detection rate of prostate cancer, and to identify the risk factors of prostate cancer detection after a 1-year administration of dutasteride and first negative prostate biopsy.Patients with benign prostatic hyperplasia who presented high prostate-specific antigen levels after the first negative prostate biopsy were administered 0.5 mg dutasteride daily for 1 year. They underwent a repeat prostate biopsy after 1 year. The primary end-point was the detection rate of prostate cancer. The secondary end-point was the ability of prostate-specific antigen kinetics to predict prostate cancer detection. Prostate-specific antigen was measured before the initial prostate biopsy and at 6, 9 and 12 months after starting dutasteride. Patients were classified into a prostate cancer and a non-prostate cancer group.Prostate cancer was detected in 15 of 149 participants (10.1%). The total prostate-specific antigen change between the prostate cancer and non-prostate cancer group at 1 year was significantly different (P = 0.002). Although prostate-specific antigen levels at baseline did not significantly differ between study groups (P = 0.102), prostate-specific antigen levels at 6, 9 and 12 months were significantly different (P = 0.002, P = 0.001 and P 0.001, respectively). The mean reduction rate of prostate-specific antigen density between the prostate cancer and non-prostate cancer group at 1 year was significantly different (-4.25 ± 76.5% vs -38.0 ± 28.7%, P = 0.001). Using a multivariate analysis, a10% increase of prostate-specific antigen density at 1 year post-dutasteride treatment was the only predictive risk factor for prostate cancer after the first negative prostate biopsy (odds ratio 11.238, 95% confidence interval 3.112-40.577, P 0.001).In the present study cohort,10% increase in prostate-specific antigen density represented the only significant predictive risk factor for prostate cancer diagnosis in patients with elevated prostate-specific antigen after the first negative prostate biopsy.

Introduction Currently, -blockers (-AB) and 5-alpha-reductase inhibitors (I-5-AR) are recommended as the drugs of choice for the treatment of patients with benign prostatic hyperplasia (BPH). However, despite the clear advantages of combination therapy, at the initial stages of treatment, I-5-AR is either not prescribed at all, or added to therapy after a few months. The aim of our study is to study the effectiveness of early and various options for delayed combined drug therapy of patients with BPH using -AB and I-5-AR. Materials and methods The study included 90 patients with BPH, who were divided into three groups of 30 people. In group 1, monotherapy with drugs from the -AB group was performed for 6 months, after which they were transferred to treatment with a combined drug. In group 2, monotherapy was performed for three months, after which they were also transferred to treatment with a combined drug. And in group 3, patients were prescribed combination therapy from day 1. Results Early combination therapy with dutasteride was more effective than delayed Therapy for 6 months. There were no significant differences in the main parameters studied between patients who simultaneously started combination therapy and switched to it after 3 months, by the end of the 12th month of treatment. However, early therapy is a combined drug made it possible to achieve a more rapid effect in relation to LUTS. Conclusion Thus, the data obtained confirm the clinical recommendations regarding the expediency of early initiation of combined therapy with an -adrenoblocker and a 5-reductase inhibitor in patients with moderate and severe LUTS caused by BPH and the risk of disease progression. Postponing the transition to combination therapy for 6 months or more may lead to a decrease in the effectiveness of treatment of patients in this category.

Background Dutasteride has been proposed as an effective therapy for frontal fibrosing alopecia (FFA). Objectives We sought to describe the therapeutic response to dutasteride and the most effective dosage in FFA compared with other therapeutic options or no treatment. Methods This was a retrospective observational study including patients with FFA with a minimum follow-up of 12 months. Therapeutic response was evaluated according to the stabilization of the hairline recession. Results A total of 224 patients (222 females) with a median follow-up of 24 months (range 12-108 months) were included. The stabilization rate for the frontal, right, and left temporal regions after 12 months was 62%, 64%, and 62% in the dutasteride group (n = 148), 60%, 35%, and 35% with other systemic therapies (n = 20), and 30%, 41%, and 38% without systemic treatment (n = 56; P = .000, .006, and .006, respectively). Stabilization showed a statistically significant association with an increasing dose of dutasteride (88%, 91%, and 84% with a weekly treatment of 5 or 7 doses of 0.5 mg [n = 32], P Limitations Limitations included the observational and retrospective design. Conclusions Oral dutasteride was the most effective therapy with a dose-dependent response for FFA in real clinical practice compared with other systemic therapies or no systemic treatment.

The objective of the present study was to develop and validate stability indicating method to generate reliable, precise, cost effective UV-VIS spectroscopy method and accurate data for dutasteride regardless of whether it is for acceptance, release, stability or pharmacokinetic study. The solvent used was methanol and the absorption maximum λ max of the drug was found to be at 241nm. A linear response was observed in the range of 1-100µg/ml. Linear regression of absorbance on concentration gave the equation y = 0.0194x + 0.0099 with a regression co-efficient (R2) of 0.997. The method was then validated for different parameters as per the ICH guidelines. Dutasteride was subjected to stress degradation under different conditions as recommended by ICH guidelines. The degradation studies were carried out by using the developed method. The method is useful for the determination of dutasteride in bulk and pharmaceutical formulations

Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions among aged men. The use of 5α-reductase inhibitors (5-ARIs) to treat BPH was linked to erectile dysfunction (ED). Many medicinal plants and secondary metabolites are used in the management of ED. Onion (Allium cepa L.) is an economically affordable vegetable with vital phytochemicals and biological functions. The study aimed to identify the beneficial effects of onion juice on dutasteride (a 5-ARI)-induced ED. Rats were divided into two groups (n = 5 per group): control and dutasteride-treated rats (0.5 mg/kg/day). Dutasteride was administered in drinking water for 12 weeks. Experiments were performed at the end of the 12th week. In vivo erectile responses were measured before and after intracavernosal injection of onion. Relaxant responses to onion juice were examined in the corpus cavernosum (CC). Acetylcholine (ACh)-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)-induced relaxation responses in CC tissues were evaluated in the absence and presence of onion juice. Total intracavernosal pressure (ICP) and ICP/ mean arterial pressure were significantly reduced in dutasteride-treated rats (1881.14 ± 249.72 mmHg, P

Background Low dose ( Aim To evaluate the role of oral minoxidil 1.25mg versus oral minoxidil 2.5mg along with platelet rich plasma in AGA METHODS: Group A consisted of fourty seven patients which included patients on OM 1.25mg daily and Platelet rich plasma therapy and Group B consisted of patients on OM 2.5 mg daily and Platelet rich plasma therapy. Photographs were taken before and after treatment along with trichoscopic evaluation. Selection of the dermoscopic variables was based on the published literature. Results At 24 weeks, marked improvement on GCP were seen in 19 (19/47;40.4%) in Group A and 28 (28/48;58.3%) patients in Group B with P value of 0.058. The total increase in total hair/cm2 was around 24 and 36 in group A and B respectively with P>0.05. The percentage increase in mean total hair count/cm2 after 6 month of treatment was 15.41% in group A and 22.15% in group B, but they were not statistically significant. The patient satisfaction score on a likert scale between both group were statistically significant. Conclusion This is a pilot study where OM along with PRP at different dosage has been compared, this can be used in patients who are a bit apprehensive on taking finasteride or dutasteride and are less responsive to topical minoxidil.

Neuroactive steroids may have a role in regulating sexual function. This case-control study assessed whether dutasteride, a 5α-reductase inhibitor used for treatment of patients with benign prostate hyperplasia (BPH), impacts on the levels of neuroactive steroids, leading to erectile dysfunction (ED) and/or hypoactive sexual desire (HSD). Forty patients with BPH and moderate-to-severe lower urinary tract symptoms (LUTS), pre-scheduled for prostate transurethral resection or open prostatectomy were enrolled. Twenty of these patients with prostate volume ≤40 mL were treated with α-blockers (Group A) and the remaining 20, with prostate volume >40 mL, with dutasteride plus α-blockers (Group B) for at least 6 months before surgery. Serum sex steroids and gonadotropin levels were measured the day before surgery, and the neuroactive steroid levels were assessed in the cerebrospinal fluid (CSF) collected during spinal anesthesia, at the day of surgery. Before surgery, the International Index of Erectile Function 5-item score was higher in Group A that Group B (18.8 ± 4.8 vs. 15.1 ± 5.4, p

Aims Combination therapy of 5α‐reductase inhibitor and α‐blocker is a guideline‐endorsed therapeutic approach for patients with moderate‐to‐severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH‐related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease‐modifying properties. Methods A time‐to‐event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin‐dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods. Results An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate‐specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin‐dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo. Conclusions Our analysis showed the implications of disease‐modifying properties of dutasteride and tamsulosin‐dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long‐term risk., Visual predictive checks. The line shows observed survival over time, whereas the shaded area describes the model predicted 95% CI for the survival. The different slopes of the survival curves for dutasteride monotherapy and combination therapy (relative to placebo) reflect the disease‐modifying properties of the intervention.

Background/aim Curcumin is a natural compound of turmeric, which inhibits prostate cancer cell proliferation. This study examined whether treatment of LNCaP prostate cancer cells with the combination of curcumin and dutasteride, a 5-alpha reductase inhibitor, affect proliferation and the amount of testosterone and dihydrotestosterone. Materials and methods LNCaP Cells were incubated with curcumin or the combination of curcumin and dutasteride and cell proliferation was measured at 72 h. LC-MS/MS was used to determine testosterone and dihydrotestosterone concentrations in prostate cancer cells. Results Curcumin combined with dutasteride suppressed proliferation and affected apoptosis of LNCaP cells. The combination of curcumin and dutasteride also reduced the amount of testosterone and dihydrotestosterone in LNCaP cells. The secretion of prostate-specific antigen was inhibited by the combination treatment in a dose-dependent manner. Conclusion Treatment with the combination of curcumin and dutasteride may interfere with the intra-tumoral androgen activity.

Objective To review and update the latest scientific evidence gathered in recent years regarding prostate-specific antigen (PSA) for better implementation into routine clinical practice. Evidence acquisition Analysis of the available evidence on the current role of PSA, based on the experience of an expert panel in the subject under analysis. Evidence synthesis Currently, PSA cannot be considered only as a guide for the presence or absence of prostate cancer. This determination can also help the urologist to decide on the most convenient treatment for a patient with benign prostatic hypertrophy (BPH) as a criterion for disease progression, and it can also suggest the suspicious existence of a prostatic tumor when there is PSA rise of >0.3 ng/ml over the level reached 6 months after having initiated treatment with 5-alpha-reductase inhibitor. However, the limits of this PSA rise with derivatives of alternative 5-alpha-reductase (5-ARI) inhibitors to dutasteride are controversial. Moreover, PSA is a key factor for the follow-up of patients with prostate adenocarcinoma at any stage who have received treatment (surgery, radiotherapy or focal therapies, hormone therapy), it acts as a guide to identify biochemical recurrence, to suspect the existence of local or distant recurrence, as well as to propose or discard adjuvant treatments. Finally, the role of PSA as a screening tool has been recently reinforced, demonstrating increased mortality rates or the existence of more aggressive cases of prostate cancer in those countries where the use of this tool has declined. Conclusions We present new data about the current role of PSA in the management of patients treated for BPH and/or prostate cancer that should be implemented into routine clinical practice, with special emphasis on the relevant role of this biomarker in the screening and follow-up of prostate cancer, as well as in the progression of BPH in dutasteride treatment.

5-Alpha-reductase inhibitors (5-ARIs) are used in the treatment of benign prostate hypertrophy (BPH). 5-ARIs, such as finasteride and dutasteride, suppress the biosynthesis of dihydrotestosterone (DHT), a precursor of androgen, which is closely related to the incidence of prostate cancer (PCa). A previous meta-analysis demonstrated a relationship between finasteride use and the incidence of PCA. However, there have been no meta-analyses on the relationship between PCa and dutasteride alone. This meta-analysis was performed to examine the prevalence of PCa in adult males taking dutasteride. We searched PubMed for reports regarding PCa risk and dutasteride use. The study was conducted according to the PRISMA guidelines for systematic reviews and meta-analyses. The analytic hierarchy process (AHP) method was used to weight the studies. Odds ratios (ORs), 95% confidence intervals (CIs), and P-values were calculated using fixed- and random-effects models. A total of eight articles were included in the meta-analysis. The overall OR for both the fixed- and random-effects models was 0.669 and the 95% CI for the random-effects model (0.526–0.851; P = 0.006) was wider than that for the fixed effects model (0.548–0.817; P < 0.001). This study confirmed that the incidence of PCa was significantly reduced by taking dutasteride.

Purpose To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. Methods Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1–24 months). AUR/S incidence was described by Kaplan–Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. Results Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p Conclusions Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.

The research work was aimed to develop a biorelevant dissolution method for fixed dose combination containing Dutasteride 0.5 mg in immediate-release form and Tamsulosin 0.4 mg in modified-release form. Mean plasma concentration achieved after oral administration to human under pre-prandial condition are deconvoluted using Wagner-Nelson deconvolution method, to achieve target dissolution profile. The dissolution profile observed using office of generic drugs recommended dissolution media was observed to be faster than the target dissolution profile. Tamsulosin being a modified-release multiparticulate system, biorelevant dissolution method was developed with Fasted state simulated change over dissolution media, using USP Apparatus 3 (reciprocating cylinder). Dutasteride being an immediate-release form, dissolution method was developed with single dissolution media, by extending the dissolution run time upto C max . Dissolution media, media volume and Dips Per Minute (DPM) are optimized by performing full factorial design of experiment. The ANOVA result interprets the biorelevant dissolution media for Tamsulosin part is 250 ml of Fasted state simulated change over dissolution media with 15 DPM, based on desirability factor of 0.7768 and for Dutasteride part 250 ml of pH 6.5 Fasted state simulated intestinal fluids with 7 DPM, based on desirability factor of 0.8988. The regression co-efficient (R 2 ) value of 0.999 and 0.996 demonstrates a very good in-vitro/in-vivo correlation under pre-prandial condition for Tamsulosin and Dutasteride respectively. The developed method shall be used as a predictive in-vitro tool for evaluation of in-vivo performance under pre-prandial condition.

This prospective double blind comparative study was designed to compare the effect of Dutasteride on the perioperative blood loss in Transurethral Resection of Prostate (TURP).Sixty patients with BPH underwent TURP were divided into 2 groups. Patients belong to the group B (Control) and group A (Experimental). Experimental group patients were given Cap. A (dutasteride 0.5 mg) before two weeks of TURP and group B (control) were given Cap. B (placebo). Postoperative comparison between two groups showed that there were no significant difference between the weight of resected prostatic tissue (control =22.41±6.83 gm, and experimental = 25.38±7.22 gm; p=0.107). Postoperative hemoglobin level of both group (Control group = 10.78±0.64 gm/dL and experimental group = 10.83±.51 gm/dL) revealed no significant difference (p=0.774). The mean hemoglobin loss per gram of prostate tissue in both groups (control = 1.81±0.81 gm/gm and experimental = 1.79±0.88 gm/gm) did not show any statistical difference (p=0.938). In this the study it was found that if the BPH patients are subjected with dutasteride 0.5mg before 2 weeks of TURP, bleeding decrease slightly (Control group = 20.35±7.99 ml/gm and Experimental groups = 17.41±7.70 ml/gm). However, these data of bleeding loss did not show any statistical significance. Bangladesh Journal of Urology, Vol. 22, No. 2, July 2019 p.177-181

Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men. Prostate-specific antigen testing is personalised (not dichotomous in nature) and its interpretation should take into account the patient's age, symptoms, previous results and medication (eg, 5-α reductase inhibitors such as dutasteride). Multiparametric magnetic resonance imaging of the prostate has been proven to have a 93% sensitivity for detecting clinically significant prostate cancer. It has the potential to decrease unnecessary prostate biopsies by around 27%. International Society of Urological Pathology (ISUP) grade 1 (Gleason score 6) has been shown to have very little, if any, risk of metastasis ISUP grade 1 (Gleason score 3 +3 = 6) and low percentage ISUP grade 2 (Gleason score 3 + 4 [

Objectives: This research work is aimed to develop bio relevant dissolution method by simulating human gastrointestinal condition at post-prandial state. The quality control dissolution procedure for modified release product using simple buffers of specific pH is not adequate for prediction of in vivo performance. Methods: Percentage of drug absorbed is derived by deconvolution of drug plasma concentration at post-prandial condition using Wagner-Nelson deconvolution method. Quality control dissolution test is performed using office of generic drugs recommended dissolution method. Bio relevant dissolution method is developed using USP Apparatus 3 (reciprocating cylinder), with quality by design approach. A full factorial design of experiment study is performed for optimization of dips per minute and media volume. Separate dissolution method is developed for tamsulosin and dutasteride, since the formulation design and release profile are different for both drugs. Results: The dissolution profile obtained using quality control procedure is observed faster in comparison to percentage of drug absorbed. The bio relevant dissolution method developed for tamsulosin part is, 250ml of Fed state simulated change over dissolution media with 15DPM, based on desirability factor 0.8767 and for dutasteride part is, 100ml of pH 6.5 Fed state simulated intestinal fluid with 20DPM, based on desirability factor 0.5836, achieved from multiple response optimizations. The dissolution results are comparable to percentage of drug absorbed. The regression co-efficient (R2) value of 0.998 and 0.982 demonstrates a very good in vitro/in vivo correlation under post-prandial condition for tamsulosin and dutasteride respectively. Conclusion: The developed method shall be used as a predictive in vitro tool for evaluation of in vivo performance under post-prandial condition.

Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme in steroid metabolism and catalyzes the reduction of testosterone to dihydrotestosterone. Mutations in the SRD5A2 gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride, as SRD5A2 inhibitors, are widely used antiandrogen drugs for benign prostate hyperplasia. The molecular mechanisms underlying enzyme catalysis and inhibition for SRD5A2 and other eukaryotic integral membrane steroid reductases remain elusive due to a lack of structural information. Here, we report a crystal structure of human SRD5A2 at 2.8 Å, revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the transmembrane domain. Structural analysis together with computational and mutagenesis studies reveal the molecular mechanisms of the catalyzed reaction and of finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region that regulate NADPH/NADP+ exchange. Mapping disease-causing mutations of SRD5A2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and may facilitate drug development., Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme and catalyzes 5α-reduction of testosterone to dihydrotestosterone. Structural analysis accompanied by computational and mutagenesis studies reveal the mechanisms of catalysis and inhibition by clinically relevant drugs targeting SRD5A2.

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.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.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).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.

5α-Reductase inhibitors reduced the risk of prostate cancer in 25% in 2 randomized trials but increased the risk of Gleason 8-10 at biopsy. One explanation is that 5α-reductase inhibitors induce morphological changes in prostate cancer cells similar to higher Gleason grades but without its adverse biology. We compared risk of prostate cancer death between men on 5α-reductase inhibitors and men not on 5α-reductase inhibitors before prostate cancer diagnosis in each Gleason Grade Group.Prostate Cancer data Base Sweden consists of linkages between the National Prostate Cancer Register, the Prescribed Drug Registry and the Cause of Death Registry. Of 89,227 men diagnosed with prostate cancer between July 2007 and December 2016, 5,816 had been on 5α-reductase inhibitors for more than 180 days before the date of diagnosis. Followup ended in December 2018. A Cox proportional hazard model was used to assess hazard ratio for prostate cancer death. Adjustments for age, comorbidity, education and curative treatment were made. Men with high risk cancer were stratified according to Gleason Grade Group.In men with high risk cancer the risk of prostate cancer death was similar among 5α-reductase inhibitor users and nonusers, with Gleason Grade Group 1 HR 1.02 (95% CI 0.53-1.95), Gleason Grade Group 2 HR 1.04 (95% CI 0.65-1.69), Gleason Grade Group 3 HR 1.27 (95% CI 0.89-1.80), Gleason Grade Group 4 HR 0.95 (95% CI 0.76-1.18) and Gleason Grade Group 5 HR 0.99 (95% CI 0.83-1.19), for 5α-reductase inhibitor users vs nonusers.We found no evidence that 5α-reductase inhibitors affect Gleason grading as no difference in mortality was observed among 5α-reductase inhibitor users and nonusers in each Gleason group.

BACKGROUND Dutasteride administration reportedly improves lower urinary tract symptoms in patient with chronic, histologically-identified prostatic inflammation, potentially through estrogen receptor β (ERβ), activation of which has anti-inflammatory effects in the prostate tissue. Therefore, we investigated the effect of dutasteride on intraprostatic inflammatory responses and bladder activity using a rat model of chemically induced prostatic inflammation. METHODS Male Sprague-Dawley rats at 10 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (control, n = 5). Rats with prostatic inflammation were divided into dutasteride therapy (dutasteride, n = 5) and placebo groups (placebo, n = 5). Dutasteride was administrated at a dose of 0.5 mg/kg daily from 2 days before induction of prostatic inflammation whereas placebo rats received vehicle only. Twenty-eight days later, cystometry was performed in a conscious condition to measure non-voiding contractions (NVCs), intercontraction intervals (ICI) and postvoid residual volume (RV). After cystometry, the prostate was excised for analysis of messenger RNA (mRNA) expression levels of ERα, ERβ, interleukin-1β (IL-1β), and IL-18 by quantitative polymerase chain reaction. RESULTS The mean number of NVCs was significantly greater in placebo group than that of control group without prostatic inflammation (p

Active surveillance (AS) provides appropriate prostate cancer (PCa)-specific survival while minimizing morbidity, but underlying worry of PCa can generate anxiety. The aim of the study is to evaluate anxiety levels in men on AS and how anxiety relates to disease characteristics and treatment decision-making. A retrospective analysis was conducted using all 302 subjects from the Reduction by Dutasteride of clinical progression Events in Expectant Management (REDEEM) study. Prostate biopsies were obtained at 18 and 36 months. Anxiety was measured at baseline and 3, 6, 12, 18, and 36 months post-randomization using the MAX-PC (Memorial general anxiety scale for PCa) questionnaire. Univariable and multivariable analysis of the association of disease aggressiveness (PSA levels, percentage of positive cores, and maximum core involvement) and anxiety levels were performed. Cox regression was used to analyze time to progression to discontinuation of active surveillance as a function of baseline anxiety. Overall, MAX-PC scores decreased from moderate at baseline with slight increases after receiving PSA results at 18 months, followed by more decline. Percentage of positive cores was associated with baseline anxiety (P = 0.02). The association remained when controlling for age, race, number of cores sampled, body mass index, prostate volume, and maximum core length (P = 0.003). In univariable and multivariable analysis, baseline anxiety was not significantly associated with time to progression to discontinuation of active surveillance. In evaluating the natural history of anxiety levels among patients with prostate cancer undergoing active surveillance, there was a decline of anxiety levels over time, with increases after receiving PSA results. Moreover, we found that disease aggressiveness measured by percentage of positive biopsy cores was associated with baseline levels of anxiety. However, anxiety had no impact on clinical or therapeutic progression.

To investigate if the PI-RADS score represents an effective tool in detecting prostate cancer in patients treated with a 5α-reductase inhibitor (dutasteride) and to identify dedicated total serum PSA and PSA density thresholds. Between April 2015 and March 2018, 75 patients under dutasteride treatment underwent multi-parametric magnetic resonance imaging (mpMRI) scans and US/MRI fusion prostate biopsy. Lesions were classified into two groups: Group 1 included PI-RADS 4 and 5 lesions, whilst Group 2 included PI-RADS 3-4-5 lesions. Lesions in groups 1 and 2 were further divided according to the patients’ history of previous prostate biopsy. Ninety-seven lesions were detected. In PI-RADS 4-5 group, mpMRI showed a sensitivity of 78.0% and a specificity of 78.7%. The positive predictive value (PPV) was 79.6% and the negative predictive value (NPV) 77.1%. In PI-RADS 3-4-5 group, sensitivity was 100%, specificity 21.3%, PPV 57.5%, NPV 100%. In PI-RADS 4-5 biopsy-naive group sensitivity was 71.4%, specificity 75.0%. PPV 78.9% and NPV 66.7%. In PI-RADS 4-5 non-biopsy-naive group sensitivity was 82.8%, specificity 80.6%, PPV 80%, and NPV 83.3%. PI-RADS 3-4-5 biopsy-naive group showed sensitivity 100%, specificity 31.3%, PPV 65.6%, NPV 100%. PI-RADS 3-4-5 non-biopsy-naive group showed sensitivity 100%, specificity 16.1%, PPV 52.7%, and NPV 100%. ROC curve analysis indicated a serum total PSA threshold of 6 ng/ml (AUC: 0.71–95% confidence interval: 0.60–0.81) and a PSA density >0.22 (AUC: 0.70–95% confidence interval: 0.6–0.81) as optimal cut-offs for recommending prostate biopsy. In our experience the PI-RADS score proved to be sufficiently accurate in predicting prostate cancer in patients under dutasteride therapy.

5-α reductase inhibitors are effective and commonly used medications for the treatment of benign prostatic hyperplasia. However, there are some questions about the safety of such medications. A post-finasteride syndrome is a controversial syndrome associated with a constellation of sexual, physical, and psychological symptoms that develop during or after finasteride exposure and persist after discontinuation. Finasteride and dutasteride have the same mechanism of action and we can suppose that the term «post-finasteride syndrome» may apply to the whole group of 5-alfa reductase inhibitors. Nowadays, reasons and development mechanisms of this syndrome are unclear. The results of studies on sexual, physical, and psychological disorders have shown mixed results. Some experts attribute post-finasteride syndrome to a group of «mysterious diseases» based on psychosocial factors. Also, we need new studies with better design because reasons and development mechanisms of this syndrome are unclear.Aleksandr A. Galushkin and Dmitriу G. Likhikh are employees GlaxoSmithKline Trading, Michael I. Kogan declares no conflict of interest.

To investigate the sexual, physical, and mental adverse effects associated with exposure to 5-alpha reductase inhibitors (5ARIs). 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. 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

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 ± 2 years; body mass index 27.1 ± 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 ± 96 vs 761 ± 57 nmol/L, P = 0.029). Prednisolone alone did not alter Ra glucose (2.55 ± 0.34 vs 2.62 ± 0.19 mg/kg/minute, P = 0.86), M-value (3.2 ± 0.5 vs 2.7 ± 0.7 mg/kg/minute, P = 0.37), or glucose oxidation (0.042 ± 0.007 vs 0.040 ± 0.004 mmol/hr/kg/minute, P = 0.79). However, co-administration with a 5α-RI increased Ra glucose (2.67 ± 0.16 vs 3.05 ± 0.18 mg/kg/minute, P 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.

The present study was an updated meta-analysis that aimed to confirm the efficacy and safety of dutasteride (0.5 mg) and finasteride (5 mg) in treating males with benign prostatic hyperplasia (BPH) over a treatment period of at least 6 months. Randomized controlled trials were retrieved using the MEDLINE, EMBASE and the Cochrane controlled trials register databases. The references of the associated articles were also searched. A systematic review was performed by using the preferred reporting items for systematic reviews and meta-analyses. The data were analyzed with RevMan v5.3.0. A total of six articles including 2,041 participants were studied. The analysis demonstrated a significantly greater decrease in international prostate symptom score [IPSS; mean difference (MD), -0.86; 95% CI, -1.62 to -0.11; P=0.02] and prostate-specific antigen (PSA; MD, -0.13; 95% CI, -0.26 to -0.01; P=0.03) in the dutasteride group compared with that in the finasteride group, whereas no significant differences were observed in prostate volume (PV; P=0.64), maximum urine flow rate (Qmax; P=0.29) and post-void residual volume (PVRV; P=0.14). With regard to safety assessment, including any adverse event (P=0.66), decreased libido (P=0.39) and impotence (P=0.17), there was no significant difference between dutasteride and finasteride. In conclusion, in patients with BPH, dutasteride produced a greater decrease in IPSS and PSA compared with finasteride, whereas no significant differences were identified in PV, Qmax and PVRV. The two drugs appeared to have similar rates of adverse effects, particularly with regard to sexual dysfunction.

Introduction: Benign Prostatic Hyperplasia (BPH) is the most common health problem of male elderly population resulting in lower urinary tract symptoms (LUTS), characterized by frequency, urgency, hesitancy, nocturia, dysuria and incomplete voiding. Aims & Objectives: To compare the different doses of petroleum ether extracts of Sphaeranthus indicus Linn (SiP) against Dutasteride, on hormonal parameters (serum testosterone and PSA) in testosterone induced BPH in albino mice. Place and Duration of study: This experimental study was conducted at the Animal House of PGMI, Lahore for 6 months. Material & Methods: Thirty-six healthy adult male mice, divided into 6 groups, were administered testosterone, different doses of petroleum ether extract SiL extracts (SIP) and dutasteride. Animals in group 1, taken as control, were given 0.1ml corn oil daily subcutaneously for 28 days. The animals in the remaining 5 groups (# 2-6) were given 3 mg/kg body weight testosterone dissolved in corn oil subcutaneously for 28 days, to induce BPH. The animals in group 3 were given 20 mg/kg/day Dutasteride orally for 28 days. Animals in groups 4-6 were given 25,50mg and 75mg/ kg body weight petroleum ether extract (SIP) orally for 28 days. Blood samples were drawn on day 0, 14 and 28 for the estimation of serum testosterone and serum PSA, by ELISA technique. Data was analyzed using SPSS Version 20.0. Comparison (between groups at baseline, day14 and day 28)was done by using one-way ANOVA and Post Hoc Tukey’s test Results: Decrease in PSA level and increase in serum testosterone supports the alpha reductase inhibiting activity of SiP, in a dose dependent manner, in testosterone induced BPH. SI petroleum ether extract 75mg/kg exhibited efficacy similar to that of dutasteride. Conclusion: Sphaeranthus indicus Linn (SiP) has shown efficacy equal to that of dutasteride in attenuating the testosterone induced BPH, in albino mice.

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 (n = 107) got tadalafil 5 mg/d as monotherapy, from the Group В (n = 107) got tadalafil 5 mg/d and solifenacin 10 mg/d, and from the Group С (n = 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), P ≤ 0.05; B: 72.4 (14.5)/102.6 (16.9), P ≤ 0.05; C: 76.6 (16.3)/109.6 (15.6), P ≤ 0.05). The level of hyperactivity symptoms decreased in Groups В and С (В: urgency −2.9 (0.7)/1.1 (0.6), P ≤ 0.05; nocturia 2.7 (1.0)/0.7 (0.5), P ≤ 0.05; C: urgency −2.5 (0.5)/0.8 (0.6), P ≤ 0.05; nocturia −2.8 (0.6)/1.0 (0.5), P ≤ 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.

Objective: This study aimed to evaluate the effect of dutasteride treatment of benign prostatic hyperplasia on serum steroidal sex hormones and prostate volume (PV). Methods: Thirty patients with benign prostate hyperplasia treated with dutasteride for one year were assessed for changes in PV and serum sex hormones (testosterone (T), dihydotestosterone (DHT), estradiol (E2) and dehydroepiandrosterone sulphate (DHEAS)). PV was measured by ultrasonography. A paired or unpaired t-test and Pearson’s correlation coefficient test were used for statistical analysis. Results: DHT and DHEAS decreased by 38.5% and 20.3%, respectively. On the contrary, T and E2 increased by 34.3% and 9.4%, respectively. PV and prostate-specific antigen decreased by 17.7% and 63.4%, respectively. The rate of decrease of DHT had a negative correlation with PV, and the rate of decrease of DHEAS had positive correlation with PV. Conclusion: DHT did not decrease as expected (previous studies showed a decrease of approximately 90%). However, DHEAS decreased more than a natural decrease. It is possible that the conversion from DHEAS to DHT, via the conversion to T, in the prostate was accelerated by the decrease of DHT, especially in larger prostates. However, this discrepancy cannot be full explained by the conversion from DHEAS to DHT, as mentioned above. Level of evidence: Level 2c

Dutasteride-Tamsulosin (DUT-TAM) is a combination drug for the treatment of symptoms of prostate enlargement (benign prostatic hyperplasia, BPH). Despite the efficacy, it is associated with some side effects, including hepatotoxicity. Therefore, this study investigated the attenuative effects of morin on DUT-TAMinduced organ toxicity. Twenty four male rats were divided into 4 groups (A-D) consisting of 6 animals each. Group A animals (control) were given olive oil, Group B animals were administered with DUT-TAM (5.4 mg/kg body weight of dutasteride + 3.4 mg/kg body weight of tamsulosin), Group C were given morin (100 mg/kg body weight) while group D animals were administered DUT-TAM and morin (5.4 mg/kg body weight dutasteride + 3.4 mg/kg body weight of Tamsulosin and 100 mg/kg body weight of morin). All the administrations were carried out orally for 14 days. DUT-TAM caused a significant increase in plasma bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by 62%, 45% and 18% in the DUT-TAM treated group respectively, compared with the control (P˂0.05). However, treatment with morin significantly decreased the DUT-TAM-induced increase in plasma bilirubin concentration as well as AST and ALT activities. Furthermore, DUT-TAM administration decreased the activities of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), as well as hepatic concentration of ascorbic acid and reduced glutathione (GSH) by 58%, 54%, 59%, 46% and 63% respectively, but increased malondialdehyde (MDA) level by 49% relative to the control (P˂0.05). However, treatment with morin significantly ameliorated the observed changes in these antioxidant parameters (P˂0.05). These data suggest that morin protects against hepatic toxicity, as well as oxidative stress induced by dutasteride-tamsulosin in rats. Keywords: Dutasteride, Tamsulosin, Prostate enlargement, Oxidative stress, Liver

Objective There are a few studies in the literature investigating the effect of preoperative dutasteride use on bleeding in open simple prostatectomy. We aimed to evaluate the effect of preoperative dutasteride use on perioperative bleeding during open simple prostatectomy. Methods We retrospectively analyzed the medical records of all patients who underwent transvesical open prostatectomy due to benign prostatic hyperplasia in our institution between 2008 and 2018. Patients were divided into 2 groups regarding the use of dutasteride prior to surgery as group 1 = received dutasteride during at least six weeks prior to surgery; group 2 = dutasteride naive.Results: A total of 167 patients who met the inclusion criteria were included in the study. The mean operative time was 86.5±18.7 min while the estimated blood loss was 640.7±55.7 ml. There was no statistically significant difference in operative time, estimated blood loss, hemoglobin, and hematocrit decrease among the two groups. Conclusion We were not able to find an advantage of pre-operative dutasteride use in terms of perioperative bleeding in open simple prostatectomy performed for benign prostatic hyperplasia.

Latar belakang: Benign Prostatic Hyperplasia (BPH) merupakan tumor jinak yang biasa dijumpai pada 1 dari 3 pria yang berusia lebih dari 50 tahun. Sedangkan Prostate Specific Antigen (PSA) adalah protein yang dihasilkan oleh kelenjar prostat yang bersifat organ spesifik dan diperiksa pada semua pasien BPH untuk mengetahui perjalanan penyakit BPH. Penggunaan obat dutasteride pada BPH dapat menghambat perubahan testosteron menjadi dihidrotestosteron serta dapat menekan pertumbuhan prostat karena obat ini termasuk dalam golongan inhibitor 5 alfa reduktase. Tamsulosin termasuk dalam golongan obat antagonis reseptor alfa 1 yang dapat merelaksasikan tonus otot polos kelenjar prostat dan leher buli-buli. Metode: Penelitian ini menggunakan desain penelitian komparatif dengan pendekatan eksperimental dan metode pengambilan data dengan pengukuran berulang (pre test – post test field trial). Pengambilan data dilakukan di Instalasi Rawat Jalan Poliklinik Bedah Urologi dan Instalasi Rekam Medis RSUD Provinsi NTB pada periode waktu Oktober 2019 sampai dengan Desember 2019. Hasil: Dari 32 responden yang dilakukan pemeriksaan PSA awal dan akhir didapatkan rata-rata kadar PSA awal terbanyak pada kelompok

Aims International Prostate Symptom Score (IPSS) is a marker of lower urinary tract symptoms (LUTS) deterioration or improvement in benign prostate hyperplasia (BPH). Whereas changes in IPSS relative to baseline have been used as endpoints in clinical trials, little attention has been given to the time course of symptoms. The current investigation aimed to develop a drug-disease model to describe individual IPSS trajectories in moderate and severe BPH patients. Methods A model-based meta-analytical approach was used including data from 10 238 patients enrolled into Phase III and IV studies receiving placebo, tamsulosin, dutasteride or combination therapy over a period of up to 4 years. Model predictive performance was assessed using statistical and graphical criteria. Subsequently, simulations were performed to illustrate the implications of treatment with drugs showing symptomatic and disease-modifying properties in patients with varying disease progression rates. Results Improvement and worsening of IPSS could be characterized by a model including a sigmoid function which disentangles drug effects from placebo and varying disease progression rates on IPSS. Mean estimate (95% confidence intervals) for the disease progression rate was 0.319 (0.271-0.411) month-1 . Treatment effect on IPSS (DELTA) was found to be 0.0605, 0.0139 and 0.0310 month-1 for placebo, tamsulosin and combination therapy, respectively. In addition, it appears that individual trajectories can be clustered together into different phenotypes describing the underlying disease progression rate (i.e. slow, moderate and fast progressors). Conclusions The availability of a drug-disease model enables the evaluation of interindividual differences in disease progression rate, deterioration of symptoms and treatment effects on LUTS/BPH.

Dutasteride (DU) (5α-reductase inhibitor) that is used for the treatment of benign prostate hyperplasia (BPH), DU has low water solubility and poor oral absorption that classified as Biopharmaceutics Classification System (BCS) class II. This study aims to improve the physical properties of Dutasteride (DU) like solubility by the preparation of microsponge (MS). Microsponges are spherical in shape, sponge-like structure, polymeric delivery systems composed of porous microspheres with a large internal surface area. Nine formulations of DU MS had been prepared by the technique of quasi-emulsion solvent diffusion (QESD) and utilizing Eudragit S100 as major polymer and glycerol as a plasticizer that dissolved in dichloromethane where polyvinyl alcohol PVA serves as a stabilizer in the external phase. The formulas were employed to optimize preparation variable factors include; different drug to polymer ratio, the addition of different concentrations of PVA, and stirring rate. Optimization was done using the response of production yield (PY), entrapment efficiency EE), particle size, and in vitro drug release; The results display that the best ratio of (drug: polymer) was 5:1, and the best rate of stirring was 1,000 rpm respecting the optimum characteristics of microsponge. The best-selected formula prepared (F2) was underwent to evaluation regarding saturated solubility, FTIR, DSC, and SEM and showed 1.28 folds enhancement in saturated solubility compared to plain DU, and was well fabricated with high entrapment efficiency (83.7% ± 1.37), production yield (85.61% ± 0.6), and particle size of 77μm. Moreover, the percent release of DU was 75.74 ± 1.5 after 4 hours, with good compatibility as confirmed by XRD, SEM, DSC, and fourier-transform infrared spectroscopy (FTIR) analysis. It can be concluded that the selected formula prepared (F2) of DU microsponge is reassuring and promising drug delivery with improved pharmaceutical physical properties.

The currently approved treatment for female pattern hair loss (FPHL) includes topical minoxidil administration; however, this treatment fails to achieve hair regrowth in some patients. Finasteride, a selective 5α-reductase inhibitor (5-ARI), may be considered as an alternative treatment. However, because of its potential teratogenic effects, clinical studies and use of finasteride for FPHL are limited. In this review, we aim to summarize the literature regarding the pharmacology, clinical efficacy, and adverse effects of oral finasteride for the treatment of FPHL and to provide novel therapeutic options including topical finasteride and dutasteride, a new generation 5-ARI, for the treatment of FPHL.

Aim: To investigate the effect of tadalafil in rats administered with daily dutasteride. Methods: Twenty-four Sprague–Dawley male rats were allocated to three groups as control (group C), dutasteride (group D) and dutasteride plus tadalafil (group D þ T). After a month of treatment, serum samples were obtained from rats to measure dihydrotestosterone and total testosterone. Nitric oxide (NO) synthase (NOS) immunoreactivity and levels of NOS enzyme isoforms, NO and cyclic guanosine monophosphate (cGMP) were evaluated in the harvested penile tissues. Also, corporal smooth muscle and collagen were examined. Results: Staining intensities of neuronal NOS and endothelial NOS were significantly lower in group D (p < .05). They were similar between group C and group D þ T. Immunoreactivity of inducible NOS was observed higher in group D than group C (p ¼ .01) whereas group D þ T had the highest iNOS (p< .001) and it was similar among group C and group D þ T (p ¼ .072). Group D had the lowest cGMP and NO levels (p < .05) and they did not differ between group C and group D þ T (p>.05). Group D and group D þ T had significantly decreased dihydrotestosterone and increased testosterone, compared to group C (p < .001). They were similar between group D and group D þ T. Conclusion: Daily treatment with tadalafil improves dutasteride-induced changes in rat penis

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.

Dutasteride and tamsulosin are one of the first-line combination therapies for the management of benign prostatic hyperplasia (BPH). Despite being more effective than monotherapies, they produce frequent adverse drug reactions (ADRs). Institutions such as Food and Drug Administration and European Medicines Agency recommend precaution with CYP2D6 poor metabolizers (PMs) that receive CYP3A4 inhibitors and tamsulosin. However, no specific pharmacogenetic guideline exists for tamsulosin. Furthermore, to date, no pharmacogenetic information is available for dutasteride. Henceforth, we studied the pharmacokinetics and safety of dutasteride/tamsulosin 0.5 mg/0.4 mg capsules according to 76 polymorphisms in 17 candidate pharmacogenes. The study population comprised 79 healthy male volunteers enrolled in three bioequivalence, phase-I, crossover, open, randomized clinical trials with different study designs: the first was single dose in fed state, the second was a single dose in fasting state, and the third was a multiple dose. As key findings, CYP2D6 PMs (i.e., *4/*4 and *4/*5 subjects) and intermediate metabolizers (IMs) (i.e., *1/*4, *1/*5, *4/*15 individuals) presented higher AUC (p = 0.004), higher t1/2 (p = 0.008), and lower Cl/F (p = 0.006) when compared with NMs (*1/*1 individuals) and UMs (1/*1 × 2 individuals) after multiple testing correction. Moreover, fed volunteers showed significantly higher tmax than fasting individuals. Nominally significant associations were observed between dutasteride exposure and CYP3A4 and CYP3A5 genotype and between tamsulosin and ABCG2, CYP3A5, and SLC22A1 genotypes. No association between the occurrence of adverse drug reactions and genotype was observed. Nonetheless, higher incidence of adverse events was found in a multiple-dose clinical trial. Based on our results, we suggest that dose adjustments for PMs and UMs could be considered to ensure drug safety and effectiveness, respectively. Further studies are warranted to confirm other pharmacogenetic associations.

Neuroinflammation is often accompanied by central nervous system (CNS) injury seen in various CNS diseases, with no specific treatment. Drug repurposing is a strategy of finding new uses for approved or investigational drugs, and can be enabled by the Library of Integrated Network-based Cellular Signatures (LINCS), a large drug perturbation database. In this study, the signatures of Lipopolysaccharide (LPS) were compared with the signatures of compounds contained in the LINCS dataset. To the top 100 compounds obtained, the Quantitative Structure-Activity Relationship (QSAR)-based tool admetSAR was used to identify the top 10 candidate compounds with relatively high blood–brain barrier (BBB) penetration. Furthermore, the seventh-ranked compound, dutasteride, a 5-α-reductase inhibitor, was selected for in vitro and in vivo validation of its anti-neuroinflammation activity. The results showed that dutasteride significantly reduced the levels of IL-6 and TNF-α in the supernatants of LPS-stimulated BV2 cells, and decreased the levels of IL-6 in the hippocampus and plasma, and the number of activated microglia in the brain of LPS administration mice. Furthermore, dutasteride also attenuated the cognitive impairment caused by LPS stimulation in mice. Taken together, this study demonstrates that the LINCS dataset-based drug repurposing strategy is an effective approach, and the predicted candidate, dutasteride, has the potential to ameliorate LPS-induced neuroinflammation and cognitive impairment.

Androgenetic alopecia (AGA) management is a significant clinical and therapeutic challenge for transgender and gender-diverse (TGD) patients. Although gender-affirming hormone therapies affect hair growth, there is little research about AGA in TGD populations. After reviewing the literature on approved treatments, off-label medication usages, and procedures for treating AGA, we present treatment options for AGA in TGD patients. The first-line treatments for any TGD patient include topical minoxidil 5% applied to the scalp once or twice daily, finasteride 1 mg oral daily, and/or low-level laser light therapy. Spironolactone 200 mg daily is also first-line for transfeminine patients. Second-line options include daily oral minoxidil dosed at 1.25 or 2.5 mg for transfeminine and transmasculine patients, respectively. Topical finasteride 0.25% monotherapy or in combination with minoxidil 2% solution are second-line options for transmasculine and transfeminine patients, respectively. Other second-line treatments for any TGD patient include oral dutasteride 0.5 mg daily, platelet-rich plasma, or hair restoration procedures. After 6-12 months of treatment, AGA severity and treatment progress should be assessed via scales not based on sex; eg, the Basic and Specific Classification or the Bouhanna scales. Dermatologists should coordinate care with the patient's primary gender-affirming clinician(s) so that shared knowledge of all medications exists across the care team.

INTRODUCTION AND OBJECTIVE:We developed a risk calculator using data from patients receiving placebo, dutasteride, tamsulosin or tamsulosin/dutasteride combination therapy coming from dutasteride t...

INTRODUCTION AND OBJECTIVE:The aim of this study was to identify the clinical factors resulting in the failure of dutasteride add-on treatment to alpha-adrenergic antagonist in patients with LUTS a...