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Archivos Espanoles de Urologia Apr 2020Although the association between 5 alpha reductase inhibitors used for the treatment of both androgenetic alopecia and benign prostatichy perplasia and their side...
OBJECTIVES
Although the association between 5 alpha reductase inhibitors used for the treatment of both androgenetic alopecia and benign prostatichy perplasia and their side effects is well established, the impact of dutasteride on testicular structure is not clear. To evaluate the alterations in spermatogenesis and serum FSH, LH, testosterone and dihydrotestosterone concentrations along with the oxidative status in testes and blood of the rats treated with daily dutasteride.
METHODS
A total of 18 male Sprague-Dawley rats have been divided into 2 groups as control (n=8) and dutasteride (n=10). After chronically administered, rats were sacrificed and their testes were harvested for histopathologica land biochemical evaluation. Johnsen's criteria were used to assess spermatogenesis. Serum hormone concentrations and levels of reactive oxygenspecies (ROS) in both testicular tissue and serum were measured by ECLIA and ELISA, respectively. Results were compared with Mann- Whitney U test.
RESULTS
DHT (7.35 ± 0.35 vs. 10.54 ± 0.95,p<0.001) and LH levels (0.32 ± 0.009vs. 0.43 ± 0.01,<0.001) were significantly lower in treatment group compared with controls where as testosterone levels were higher in dutasteride arm (3.41 ± 1.12 vs.1.52 ± 0.34, p<0.001). Johnsen score, serum FSH levels, serum and tissue ROS levels were similar betweenthe two groups.
CONCLUSIONS
According to our results, administration of dutasteride does not appear to modify spermatogenesis and oxidative burden in rats. Further investigations are required to confirm our findings.
Topics: 5-alpha Reductase Inhibitors; Animals; Dutasteride; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spermatogenesis; Testis; Testosterone
PubMed: 32240114
DOI: No ID Found -
Medicine Nov 2022We performed a retrospective study to clarify the characteristics of prostate biopsies in patients treated with dutasteride, a benign prostate hyperplasia treatment drug...
We performed a retrospective study to clarify the characteristics of prostate biopsies in patients treated with dutasteride, a benign prostate hyperplasia treatment drug that inhibits 5α-reductase. We studied the digital clinical data of 677 patients, including 96 cases treated with dutasteride, with suspected localized prostate cancer. All patients underwent transrectal ultrasonography-guided prostate biopsy between 2014 and 2017 in our department. A propensity score matching analysis was performed based on prostate-specific antigen (PSA) (calculated as double the PSA value for the dutasteride group) and age. Ninety-six patients in each of the dutasteride and control groups were assessed and their characteristics were compared. The characteristics of the patients in the dutasteride and control groups were well balanced by matching. There were fewer prostate cancer-positive patients in the dutasteride group. When comparing only the prostate cancer-positive patients in each group, there were significantly more cases of high-grade cancers and abnormal magnetic resonance imaging (MRI) findings in the dutasteride group. In the dutasteride group, abnormal MRI findings and advanced age were significant predictors of high grade cancer. This study shows the characteristics of prostate biopsies in patients treated with dutasteride and indicates that patients on dutasteride with advanced age and abnormal MRI findings should undergo prostate biopsy.
Topics: Male; Humans; Dutasteride; Prostate; Prostate-Specific Antigen; Azasteroids; 5-alpha Reductase Inhibitors; Retrospective Studies; Biopsy; Prostatic Neoplasms
PubMed: 36343082
DOI: 10.1097/MD.0000000000031658 -
F1000Research 2021Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including... (Review)
Review
Prostate cancer (CaP) is one of the leading causes of death in men worldwide. Much attention has been given on its prevention and treatment strategies, including targeting the regulation of 5-alpha-Reductase (5αR) enzyme activity, aimed to limit the progression of CaP by inhibiting the conversion of potent androgen dihydrotestosterone from testosterone that is thought to play a role in pathogenesis of CaP, by using the 5-alpha-Reductase inhibitors (5αRis) such as finasteride and dutasteride. However, 5αRis are reported to exhibit numerous adverse side effects, for instance erectile dysfunction, ejaculatory dysfunction and loss of libido. This has led to a surge of interest on plant-derived alternatives that might offer favourable side effects and less toxic profiles. Phytochemicals from plants are shown to exhibit numerous medicinal properties in various studies targeting many major illnesses including CaP. Therefore, in this review, we aim to discuss the use of phytochemicals namely phytosterols, polyphenols and fatty acids, found in various plants with proven anti-CaP properties, as an alternative herbal CaP medicines as well as to outline their inhibitory activities on 5αRs isozymes based on their structural similarities with current 5αRis as part of CaP treatment approaches.
Topics: Cholestenone 5 alpha-Reductase; Humans; Male; Oxidoreductases; Phytochemicals; Prospective Studies; Prostatic Neoplasms
PubMed: 34316358
DOI: 10.12688/f1000research.51066.3 -
Translational Andrology and Urology Mar 2022Although the efficacy and safety of monotherapy in the treatment of benign prostatic hyperplasia (BPH) have been established clinically, the efficacy and safety of...
BACKGROUND
Although the efficacy and safety of monotherapy in the treatment of benign prostatic hyperplasia (BPH) have been established clinically, the efficacy and safety of dutasteride and finasteride have not been compared. The aim was to systematically evaluate the efficacy and safety of the two drugs in the treatment of BPH to provide medical evidence for clinical treatment.
METHODS
A search of relevant articles was conducted using the electronic databases PubMed, Embase, Medline, Cochrane Library, China Academic Journals Full-text Database (CJFD), Chinese Science and Technology Journal Database (VIP) and Wanfang Database. Randomized controlled trials (RCTs) comparing the efficacy of finasteride (control group) with that of dutasteride (experimental group) in the treatment of BPH with respect to the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), prostate volume (PV), quality of life (QOL), serum prostate-specific antigen (PSA) level and adverse drug reactions (ADRs) after medication were strictly evaluated and considered for inclusion. Rev Man 5.4 software was used for the meta-analysis.
RESULTS
A total of 8 RCTs were included, with a total of 2,116, patients. The meta-analysis showed that compared with finasteride, dutasteride can effectively improve the Qmax of patients with BPH [mean difference (MD) =0.32; 95% confidence interval (CI): (0.01, 0.63); P=0.04]. There was no significant difference in reducing IPSS [MD =0.13; 95% CI: (-0.55, 0.82); P=0.70], improving PV [MD =-1.25; 95% CI: (-3.30, 0.79); P=0.23], reducing QOL [MD =-0.44; 95% CI: (-0.93, 0.05); P=0.08] and serum PSA level [MD =-0.04; 95% CI: (-0.15, 0.07); P=0.50], and the occurrence of ADRs [relative risk (RR) =-0.01; 95% CI: (-0.05, 0.04); P=0.72], there was no significant difference.
DISCUSSION
Dutasteride is better than finasteride in improving the Qmax of patients with BPH. There was no statistically significant difference in symptoms, PV, PSA, QOL, or adverse reactions. Dutasteride is an effective and safe treatment for BPH. Due to the limitations of the methodological quality and sample size of the included studies, this conclusion needs to be verified by stratified RCTS with high volumes and long follow-up times.
PubMed: 35402192
DOI: 10.21037/tau-22-58 -
Experimental Neurology May 2023Growing preclinical and clinical evidence highlights neurosteroid pathway imbalances in Parkinson's Disease (PD) and L-DOPA-induced dyskinesias (LIDs). We recently...
Growing preclinical and clinical evidence highlights neurosteroid pathway imbalances in Parkinson's Disease (PD) and L-DOPA-induced dyskinesias (LIDs). We recently reported that 5α-reductase (5AR) inhibitors dampen dyskinesias in parkinsonian rats; however, unraveling which specific neurosteroid mediates this effect is critical to optimize a targeted therapy. Among the 5AR-related neurosteroids, striatal pregnenolone has been shown to be increased in response to 5AR blockade and decreased after 6-OHDA lesions in the rat PD model. Moreover, this neurosteroid rescued psychotic-like phenotypes by exerting marked antidopaminergic activity. In light of this evidence, we investigated whether pregnenolone might dampen the appearance of LIDs in parkinsonian drug-naïve rats. We tested 3 escalating doses of pregnenolone (6, 18, 36 mg/kg) in 6-OHDA-lesioned male rats and compared the behavioral, neurochemical, and molecular outcomes with those induced by the 5AR inhibitor dutasteride, as positive control. The results showed that pregnenolone dose-dependently countered LIDs without affecting L-DOPA-induced motor improvements. Post-mortem analyses revealed that pregnenolone significantly prevented the increase of validated striatal markers of dyskinesias, such as phospho-Thr-34 DARPP-32 and phospho-ERK, as well as D-D receptor co-immunoprecipitation in a fashion similar to dutasteride. Moreover, the antidyskinetic effect of pregnenolone was paralleled by reduced striatal levels of BDNF, a well-established factor associated with the development of LIDs. In support of a direct pregnenolone effect, LC/MS-MS analyses revealed that striatal pregnenolone levels strikingly increased after the exogenous administration, with no significant alterations in downstream metabolites. All these data suggest pregnenolone as a key player in the antidyskinetic properties of 5AR inhibitors and highlight this neurosteroid as an interesting novel tool to target LIDs in PD.
Topics: Male; Rats; Animals; Levodopa; Parkinson Disease; Dutasteride; Oxidopamine; Neurosteroids; Rats, Sprague-Dawley; Dyskinesia, Drug-Induced; Corpus Striatum; Antiparkinson Agents; Disease Models, Animal
PubMed: 36878398
DOI: 10.1016/j.expneurol.2023.114370 -
Medical Archives (Sarajevo, Bosnia and... Feb 2023Following the c In the management of BPH, Tamsulosin is an example of a-adrenergic receptor blocker drug that is usually used. In addition, dutasteride is also a BPH...
The Effect of Tamsulosin, Dutasteride Monotherapy and Tamsulosin-Dutasteride Combination on Prostate Smooth Muscle Contractility in BPH Model Wistar Strain Rattus Novergicus.
BACKGROUND
Following the c In the management of BPH, Tamsulosin is an example of a-adrenergic receptor blocker drug that is usually used. In addition, dutasteride is also a BPH drug that works as a group of 5 a reductase inhibitor. However, the weakness of long-term administration of a1-adrenergic receptor antagonists can result in upregulation of prostate smooth muscle cell contractility and expression of a-adrenergic mRNA receptors, resulting in hyperactivity and supersensitivity to a-agonists.
OBJECTIVE
Our study aimed to determine the effect of long-term administration of tamsulosin, dutasteride and tamsulosin-dutasteride combination on the contractility of prostate smooth muscle cells in BPH model rats.
METHODS
This study was designed using an experimental post test only method, control group design. It measured the contractility of prostate smooth muscle cells from samples obtained from the prostatic stroma of experimental animals adult male Rattus norvegicus Wistar strain induced BPH and administered tamsulosin 1 mg/kg/day, dutasteride 0.5 mg/kg/day, and a combination of continuous administration for 1, 6 and 12 consecutive days. Data were analyzed using one way ANOVA if the data distribution was normal or Kruskall Walis if the data distribution was abnormal.
RESULT
The effect of tamsulosin, dutasteride and the combination of tamsulosin with dutasteride on prostate smooth muscle cell contractility in experimental animals Rattus norvegicus Wistar strain showed that tamsulosin administration for six days, twelve days, and the combination of tamsulosin dutasteride for one day got statistically significant different result (p=0.016; p=0.006; p=0.029) compared to the negative control group. In addition, there was a difference between the tamsulosin and dutasteride combination group for 12 days compared to tamsulosin monotherapy for 6 days and 12 days (p=0.160; p=0.010).
CONCLUSION
Continuous administration of monotherapy tamsulosin has an upregulation effect on the sixth to twelfth day. Decreased contractility of prostate smooth muscle cells occurs on the first day but will increase on the sixth to twelfth day. On the other hand, the results of our study also showed that the combination of tamsulosin and dutasteride gave the effect of reducing contractility and was most effective on day 12.
Topics: Humans; Male; Animals; Rats; Dutasteride; Tamsulosin; Prostatic Hyperplasia; Prostate; 5-alpha Reductase Inhibitors; Azasteroids; Sulfonamides; Drug Therapy, Combination; Rats, Wistar; Muscle, Smooth
PubMed: 36919125
DOI: 10.5455/medarh.2023.77.13-17 -
Neurobiology of Stress May 2020The presence of side effects during pharmacological treatment is unfortunately a quite common problem. In this review, we focused our attention on adverse events related...
The presence of side effects during pharmacological treatment is unfortunately a quite common problem. In this review, we focused our attention on adverse events related to 5 alpha-reductase (5α-R) inhibitors (i.e., finasteride and dutasteride), approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia (AGA). Although these drugs are generally well tolerated, many reports described adverse effects in men during treatment, such as sexual dysfunction and mood alteration. In addition, it has been also reported that persistent side effects may occur in some AGA patients. This condition, termed post-finasteride syndrome (PFS) is characterized by sexual side effects (i.e., low libido, erectile dysfunction, decreased arousal and difficulty in achieving orgasm), depression, anxiety and cognitive complaints that are still present despite drug withdrawal. Indeed, some national agencies (e.g., Swedish Medical Products Agency, the Medicines and Healthcare Products Regulatory Agency of UK and the U.S. Food and Drug Administration) required to include multiple persistent side effects within the finasteride labels. As here reported, these observations are mainly based on self-reporting of the symptomatology by the patients and few clinical studies have been performed so far. In addition, molecular mechanisms and/or genetic determinants behind such adverse effects have been poorly explored both in patients and animal models. Therefore, results here discussed indicate that PFS is an emerging clinical problem that needs to be further elucidated.
PubMed: 32435662
DOI: 10.1016/j.ynstr.2019.100209 -
Iranian Journal of Allergy, Asthma, and... Oct 2022Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation...
Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β), and nitric oxide (NO) in the Lipopolysaccharides (LPS)-stimulated U-87 MG cell line. Human astrocytoma U-87 MG cell line was cultured and incubated with 10 μg/mL of LPS for 24 hours to create a neuro-inflammation model, using two different treatment approaches. The first approach included LPS treatment for 24 hours, followed by dutasteride (20 μg/mL) incubation for the next 72 hours. In the second treatment approach, the cells were co-incubated with LPS and dutasteride for 72 hours. Expression of TLR4, MyD88, NF-κBp65, and secretory IL-1 was evaluated by Western blotting while expression of NO was assessed by NO assay. TLR4, MyD88, NF-κBp65, and secretory IL-1β levels increased in LPS-treated cells after 24 hours. Dutasteride significantly decreased the secretion of NO and also, the levels of TLR4, MyD88, and NF-κBp65 in both treatment approaches. No difference in IL-1β level was seen with the second treatment approach. Dutasteride has anti-inflammatory properties and probably analgesic effects, by mechanisms different from conventional analgesics.
Topics: Humans; Toll-Like Receptor 4; Lipopolysaccharides; Myeloid Differentiation Factor 88; Dutasteride; Signal Transduction; NF-kappa B; Pain
PubMed: 36341565
DOI: 10.18502/ijaai.v21i5.11044 -
Frontiers in Pharmacology 2021Dutasteride and tamsulosin are one of the first-line combination therapies for the management of benign prostatic hyperplasia (BPH). Despite being more effective than...
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 poor metabolizers (PMs) that receive 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, 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 ( = 0.004), higher t ( = 0.008), and lower Cl/F ( = 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 t than fasting individuals. Nominally significant associations were observed between dutasteride exposure and and genotype and between tamsulosin and , , and 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.
PubMed: 34690761
DOI: 10.3389/fphar.2021.718281 -
Journal of Clinical Medicine May 2024The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral... (Review)
Review
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.
PubMed: 38892763
DOI: 10.3390/jcm13113052