Benign prostatic hyperplasia nodules in patients treated with celecoxib and/or finasteride have reduced levels of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, a mitochondrial protein essential for efficient function of the electron transport chain.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase-2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH-associated LUTS. METHODS: To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed. RESULTS: NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration. CONCLUSIONS: These findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.

Vesical Endometriosis in a male patient on treatment for papillary urothelial carcinoma.

Endometriosis denotes the abnormal growth of tissue resembling endometrium in ectopic sites and has largely been studied in women of reproductive age. It is an extremely rare phenomenon in men. We came across an exceptional clinical scenario of histologically proven bladder endometriosis in a 66-year-old man in relook bladder biopsy following completion of adjuvant intravesical Bacillus Calmette-Guerin induction course for G3pTa bladder cancer. We have pencilled down pathophysiology and commonly seen predisposing factors for "endometriosis in male patients" from available case reports and applied those findings to hypothesise the disease profile of our patient in this case report.

A bibliometric analysis of alternative drug therapy options in the treatment of androgenetic alopecia.

BACKGROUND: Oral finasteride and topical minoxidil formulations are the only FDA-approved drug therapies for androgenetic alopecia (AGA). Research into dutasteride, topical finasteride, and nontopical minoxidil (low-dose oral and sublingual) formulations in the treatment of AGA has spiked within recent years. Early findings show that these alternative drug therapies may have similar to improved efficacy and safety profiles relative to the conventional treatment options. AIMS: Conducting a bibliometric analysis, compare trends in publications on these alternative drug therapies, identify key contributors, evaluate major findings from top-cited articles, and elucidate gaps in evidence. METHODS: A search was conducted on the Web of Science database for publications on the use of alternative drug therapies in the treatment of AGA. A total of 95 publications, published between January 2003-March 2024, and their citation metadata were included in the analysis. RESULTS: Dutasteride showed the greatest (n = 37) and longest (20+ years) history of publications, as well as the highest cumulative citations (n = 914); however, nontopical minoxidil showed a burst in research activity within the last 5 years (n = 33 publications since 2019). A relatively low number of randomized control trials (n = 3) for nontopical minoxidil suggests a need for higher-quality evidence. CONCLUSIONS: Our analysis reveals major trends, contributors, and gaps in evidence for alternative drug therapies for AGA, which can help inform researchers on their future projects in this growing field of study. There is enthusiasm for exploring off-label formulations: nontopical forms of minoxidil (oral and sublingual), topical finasteride, and mesotherapy.

Management of androgenic alopecia: a systematic review of the literature.

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

Safety of Antiandrogens for the Treatment of Female Androgenetic Alopecia with Respect to Gynecologic Malignancies.

The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol.

Adverse effects of the 5-alpha-reductase inhibitor finasteride on Daphnia magna: Endocrine system and lipid metabolism disruption.

Finasteride, a steroid 5-alpha reductase inhibitor, is commonly used for the treatment of benign prostatic hyperplasia and hair loss. However, despite continued use, its environmental implications have not been thoroughly investigated. Thus, we investigated the acute and chronic adverse impacts of finasteride on Daphnia magna, a crucial planktonic crustacean in freshwater ecosystems selected as bioindicator organism for understanding the ecotoxicological effects. Chronic exposure (for 23 days) to finasteride negatively affected development and reproduction, leading to reduced fecundity, delayed first brood, reduced growth, and reduced neonate size. Additionally, acute exposure (< 24 h) caused decreased expression levels of genes crucial for reproduction and development, especially EcR-A/B (ecdysone receptors), Jhe (juvenile hormone esterase), and Vtg2 (vitellogenin), with oxidative stress-related genes. Untargeted lipidomics/metabolomic analyses revealed lipidomic alteration, including 19 upregulated and 4 downregulated enriched lipid ontology categories, and confirmed downregulation of metabolites. Pathway analysis implicated significant effects on metabolic pathways, including the pentose phosphate pathway, histidine metabolism, beta-alanine metabolism, as well as alanine, aspartate, and glutamate metabolism. This comprehensive study unravels the intricate molecular and metabolic responses of D. magna to finasteride exposure, underscoring the multifaceted impacts of this anti-androgenic compound on a keystone species of freshwater ecosystems. The findings emphasize the importance of understanding the environmental repercussions of widely used pharmaceuticals to protect biodiversity in aquatic ecosystems.

Is There an Association between 5a Reductase Inhibitors and Metabolic Syndrome? A Narrative Review of the Literature.

Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms.

A Phase I, Open-Label, Sequential, Single-Dose Clinical Trial to Evaluate the Pharmacokinetic, Pharmacodynamic, and Safety of IVL3001, a Finasteride-Based Novel Long-Acting Injection for Androgenetic Alopecia.

INTRODUCTION: Hair loss is driven by multiple factors, including genetics. Androgenetic alopecia (AGA) is a condition in which treatments necessitate prolonged compliance with prescribed medications. We have developed IVL3001, a long-acting injectable (LAI) formulation of finasteride encapsulated within poly lactic-co-glycolic acid microspheres, to enhance the efficacy of the finasteride and to achieve consistent positive outcomes in adults. An open-label, sequential, single-dose phase I clinical trial was designed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) of IVL3001. METHODS: A total of 40 non-smoking, healthy adult males were divided into three cohorts where the IVL3001 group received a single subcutaneous injection of 12-36 mg IVL3001 and 1 mg finasteride (Propecia®) once daily for 28 days. The plasma concentrations of finasteride, dihydrotestosterone (DHT), and testosterone were measured using liquid chromatography-tandem mass spectrometry. The tolerability of the injections was assessed, and compartment models were developed to predict the effective dose and assess PK/PD profiles. RESULTS: IVL3001 and finasteride 1 mg tablets were well tolerated. IVL3001 showed consistent plasma concentrations without bursts or fluctuations. Consistent with its mechanism of action, IVL3001 reduced DHT levels. Simulation data showed that the administration of 12-36 mg of IVL3001 every 4 weeks achieved plasma concentrations similar to finasteride, with comparable DHT reduction. CONCLUSION: The present study represents the first clinical trial to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD), and tolerability of finasteride long-acting injectables (LAI) in adults. The rapid onset of action sustained effective drug concentration and the prolonged half-life of IVL3001 suggest that it offers multiple benefits over conventional oral formulations in terms of therapeutic response and compliance. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04945226.

An Unusual Case of Thalamic Stroke in a Young Adult With Patent Foramen Ovale and Finasteride Use.

Symptomatic cerebral infarcts with cryptogenic ischemic stroke pose diagnostic challenges due to unknown etiology. Notably, up to half of young individuals with cryptogenic stroke exhibit patent foramen ovale (PFO), while finasteride, which is used for male pattern baldness, elevates testosterone levels, potentially increasing the risk of thrombosis. Here, we present a case of thalamic infarction in a 21-year-old male devoid of cerebrovascular risk factors but with PFO and finasteride use. The patient presented with short-term memory issues, otherwise lacking medical history or substance use. Examination revealed neurological deficits, with imaging indicating a left thalamic infarct. Subsequent investigations identified PFO, prompting referral for closure, yielding symptomatic improvement. Furthermore, discontinuation of finasteride was advised due to its thrombotic association. Finasteride's inhibition of 5-alpha reductase 2 increases testosterone conversion to estrogen, potentially promoting thrombosis. Finasteride use can cause thrombotic events, emphasizing its risk. In conclusion, young embolic stroke patients warrant PFO evaluation alongside hypercoagulable workup, with closure benefiting those under the age of 55. Additionally, discontinuing finasteride may mitigate thrombosis risk.

Patient-reported outcomes of topical finasteride/minoxidil treatment for male androgenetic alopecia: A retrospective study using telemedical data.

BACKGROUND: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking. AIMS: To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride). METHODS: Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment. RESULTS: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events. CONCLUSION: Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil.

Association of 5α-Reductase Inhibitors with Depression and Suicide: A Mini Systematic Review and Meta-analysis.

5α-Reductase inhibitors (5-ARIs) are widely prescribed for treatment of benign prostatic obstruction and androgenic alopecia. Several studies with controversial findings regarding 5-ARI exposure have been published over a number of years, and concerns were recently raised about the potential risks of depression and suicide associated with 5-ARIs. To investigate this association, we conducted a systematic review of the literature and a meta-analysis. Five studies involving 2213600 patients met our inclusion criteria. We found no statistically significant association between 5-ARI exposure and the risk of depression (adjusted hazard ratio [aHR] 1.30, 95% confidence interval [CI] 0.85-2.00; p = 0.23) or suicide (aHR 1.30, 95% CI 0.65-2.61; p = 0.45). Subgroup analyses for finasteride and dutasteride revealed similar results. When restricting the analysis to patients without a prior diagnosis of depression, we observed similar findings (aHR for suicide 1.00, 95% CI 0.68-1.46; p = 0.98). PATIENT SUMMARY: We reviewed study data for more than two million patients taking drugs called 5α-reductase inhibitors (5-ARIs), which are widely prescribed for urinary problems caused by benign prostate enlargement and for male-pattern hair loss. In a pooled analysis we found no evidence of an association between 5-ARI use and the risk of depression or suicide.

Comparison of Finasteride and Dutasteride on Risk of Prostate Cancer in Patients with Benign Prostatic Hyperplasia: A Pooled Analysis of 15 Real-world Databases.

PURPOSE: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. MATERIALS AND METHODS: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. RESULTS: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44-1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67-1.14; p=0.310). CONCLUSIONS: Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

In vitro inhibition of 5-α reductase and in vivo suppression of benign prostatic hyperplasia by Physalis angulata ethyl acetate extract.

The inhibitory effect against 5-α reductase of the ethyl acetate (EA) extract from Physalis angulata was evaluated in vitro using mouse prostate homogenates, and the suppression of benign prostatic hyperplasia (BPH) was assessed in a mouse model of testosterone-induced BPH. The EA extract exhibited a potentially inhibitory effect on 5-α reductase with an IC50 of 197 µg/ml. In BPH mice, the EA extract at a dose of 12 mg/kg was comparable to finasteride 5 mg/kg in suppressing BPH in terms of reducing absolute enlarged prostate weight (p < 0.05 vs. BPH group) and mitigating the hypertrophy of glandular elements and prostate connective tissue. Identification of chemical ingredients in the EA extract by UPLC-QTOF-MS revealed 37 substances belonging chiefly to flavonoids and physalins. Further quantification of the EA extract by HPLC-PDA methods revealed that chlorogenic acid, and rutin were the main components. Molecular docking studies of chlorogenic acid and rutin on 5-α reductase showed their high affinity to the enzyme with binding energies of -9.3 and - 9.2 kcal/mol, respectively compared with finasteride (- 10.3 kcal/mol). Additionally, chlorogenic acid inhibited 5-α reductase with an IC50 of 12.07 µM while rutin did not. The presence of chlorogenic acid in the EA extract may explain the inhibitory effects of the EA extract on 5-α reductase, and thus the suppression of BPH.

Persistent Gynecomastia due to Short-term Low-dose Finasteride for Androgenetic Alopecia.

We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did not resolve after 6 months of treatment with raloxifene, a selective estrogen receptor modulator. One year later, bilateral mammoplasty was performed to remove the remaining breast tissue. Finasteride, a 5-alpha-reductase inhibitor, is widely used for the treatment of androgenetic alopecia. Gynecomastia is an expected side effect of this therapy given its mechanism of action. However, only 8 cases of gynecomastia have been reported with low-dose (1 mg daily) finasteride treatment since its approval for androgenetic alopecia in 1997. This raises the concern that gynecomastia resulting from low-dose finasteride is significantly underreported, causing inadequately informed patients. Further, because of the risk of gynecomastia, it is important for prescribing physicians to counsel patients regarding this complication and to consider early intervention when finasteride-induced gynecomastia first arises to prevent fibrosis and thus irreversible gynecomastia.

Analysis of the finasteride treatment and its withdrawal in the rat hypothalamus and hippocampus at whole-transcriptome level.

PURPOSE: As reported in patients treated for androgenetic alopecia with finasteride (i.e., a blocker of the enzyme 5 alpha-reductase) and in an animal model, side effects affecting sexual, psychiatric, neurological, and physical domains, may occur during the treatment and persist with drug suspension. The etiopathogenesis of these side effects has been poorly explored. Therefore, we performed a genome-wide analysis of finasteride effects in the brain of adult male rat. METHODS: Animals were treated (i.e., for 20 days) with finasteride (1mg/rat/day). 24 h after the last treatment and 1 month after drug suspension, RNA sequencing analysis was performed in hypothalamus and hippocampus. Data were analyzed by differential expression analysis and Gene-Set Enrichment Analyses (GSEA). RESULTS: Data obtained after finasteride treatment showed that 186 genes (i.e., 171 up- and 15 downregulated) and 19 (i.e., 17 up- and 2 downregulated) were differentially expressed in the hypothalamus and hippocampus, respectively. Differential expression analysis at the drug withdrawal failed to identify dysregulated genes. Several gene-sets were enriched in these brain areas at both time points. CONCLUSION: Some of the genes reported to be differentially expressed (i.e., TTR, DIO2, CLDN1, CLDN2, SLC4A5, KCNE2, CROT, HCRT, MARCKSL1, VGF, IRF2BPL) and GSEA, suggest a potential link with specific side effects previously observed in patients and in the animal model, such as depression, anxiety, disturbance in memory and attention, and sleep disturbance. These data may provide an important background for future experiments aimed at confirming the pathological role of these genes.

Effect of 5-Alpha Reductase Inhibitors on Magnetic Resonance Imaging and Prostate Cancer Detection.

Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure (p 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively (p 0.596). IPCa was detected in 37.6 and 62.5%, respectively (p 0.089). The tumor GG distribution based on 5-ARI exposure was similar (p 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.

Therapeutic effects of finasteride: inhibition of disease progression and serum prostate-specific antigen reduction in patients with prostatic intraepithelial neoplasia.

The objective of this study was to evaluate the impact of finasteride on the progression of prostate intraepithelial neoplasia and levels of prostate-specific antigen (PSA) in patients. A total of 120 patients with high-grade prostatic intraepithelial neoplasia were included in this study from January 2013 to January 2018. All patients underwent prostate biopsies. Among them, 60 patients were assigned to the observation group and received a daily dosage of 5 mg finasteride for 60 months, while the remaining 60 patients were assigned to the control group and did not receive finasteride. PSA levels were measured every six months, and imaging scans were conducted throughout the five-year study period. Additional biopsies were performed if PSA levels exceeded 10 ng/mL or imaging suggested the presence of prostate cancer. Statistical analysis was applied to the collected data. In total, 25 cases of prostate cancer were identified in this study. Of these cases, 7 patients belonged to the observation group, whereas the remaining 18 patients were from the control group. The observation group exhibited significantly lower levels of total serum PSA (p < 0.001) and Gleason scores (p < 0.001) compared to the control group. Our study, which involved 120 participants, demonstrated that finasteride effectively reduces serum PSA levels and mitigates the severity of prostate cancer. These findings suggest that finasteride holds potential as a treatment option for patients with -high-grade prostatic intraepithelial neoplasia.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

Tadalafil versus tamsulosin as combination therapy with 5-alpha reductase inhibitors in benign prostatic hyperplasia, urinary and sexual outcomes.

PURPOSE: To compare the urological and sexual outcomes of using either tamsulosin/finateride or tadalafil/finasteride as combination therapies in patients with large prostate. PATIENTS AND METHODS: Selection criteria included prostate volume > 40 ml and IPSS > 7. Patients with severe erectile dysfunction (IIEF-erectile functions ≤ 10) were excluded. Patients were randomized into group I (tamsulosin/finasteride) and group II (tadalafil/finasteride). The primary endpoint was to define urinary and sexual function changes (IPSS, IPSS-quality of life, urinary flow rates and IIEF domains) within each group. The secondary endpoint was to compare the treatment induced changes between both groups. RESULTS: At 4th and 12th weeks, 131 and 127 patients were available in both groups, respectively. Both groups showed significant LUTS improvement (IPSS changes: - 4.9 ± 2.7 and - 4.3 ± 2.9 at 4th week and - 6.1 ± 3 and - 5.4 ± 2.8 points by the 12th week in both groups, respectively). Group I had better average flow rates at both follow-up visits. Meanwhile, maximum flow rates were comparable in both groups at 12th week (13.5 ± 3.9vs. 12.6 ± 3.7, p > 0.05). In group I, all IIEF domains were significantly lowered at both visits (p < 0.05). Group II showed significant increase in IIEF-erectile function scores (1.3 ± 1.1 and 1.8 ± 1.2 at the 4th and 12th weeks) with a transient significant reduction of IIEF-orgasm and sexual desire noted only by the 4th week (- 0.8 ± 0.4 and - 0.6 ± 0.4, respectively). CONCLUSION: Within three months, both combinations are comparably effective in improving BPH related LUTS. Tamsulosin/finasteride provided significantly better Qmax only at 4th week. Tadalafil/finasteride had the advantage of improving sexual performance over the other combination.