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Scientific Reports Dec 2022Caffeic acid derivatives containing amide moieties similar to those of finasteride and dutasteride were synthesized. An in vitro inhibitory activity evaluation of...
Caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide as a non-steroidal inhibitor for steroid 5α-reductase type 1 using a human keratinocyte cell-based assay and molecular dynamics.
Caffeic acid derivatives containing amide moieties similar to those of finasteride and dutasteride were synthesized. An in vitro inhibitory activity evaluation of caffeic acid (1) and its amide derivatives (2 - 4) against the steroid 5α-reductase type 1 (SRD5A1) produced by human keratinocyte cells coupled with the non-radioactive high-performance thin-layer chromatography detection revealed that caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide (4) was a promising non-steroidal suppressor, with a half-maximal inhibitory concentration (IC) of 1.44 ± 0.13 µM and relatively low cytotoxicity with an IC of 29.99 ± 8.69 µM. The regulatory role of compound 4 against SRD5A1 involved both suppression of SRD5A1 expression and mixed mode SRD5A1 inhibition. The K value of compound 4 was 2.382 µM based on the whole-cell kinetic studies under specific conditions. Molecular docking and molecular dynamics simulations with AlphaFold generated the human SRD5A1 structure and confirmed the stability of compound 4 at the SRD5A1 catalytic site with greater interactions, including hydrogen bonding of the key M119 amino-acid residue than those of finasteride and dutasteride. Thus, compound 4 shows the potential for further development as an SRD5A1 suppressor for androgenic alopecia treatment.
Topics: Humans; Molecular Dynamics Simulation; Amides; Molecular Docking Simulation; Finasteride; Dutasteride; Kinetics; Keratinocytes
PubMed: 36460729
DOI: 10.1038/s41598-022-25335-7 -
Postgraduate Medicine Mar 2023The present study aims to analyze the impact of prescriptions on the incidence of urinary incontinence, polyuria (including nocturia), urinary retention, and erectile...
The present study aims to analyze the impact of prescriptions on the incidence of urinary incontinence, polyuria (including nocturia), urinary retention, and erectile dysfunction in a real-world setting in Germany and to compare these data with data for the 5-ARIs finasteride and dutasteride, and the α1-adrenoceptor antagonists tamsulosin and tamsulosin/dutasteride fixed-dose combination. This retrospective study was based on the IQVIA Disease Analyzer database and included male patients with an initial prescription of , finasteride, dutasteride, tamsulosin, or tamsulosin/dutasteride fixed-dose combination between January 2010 and September 2020. Multivariable logistic regression analyses adjusted for age, health insurance, specialty, and relevant co-diagnoses were performed to estimate the association between prescriptions and incidence of pre-defined outcomes. A total of 77,923 patients were included in the study, 3,035 of whom received was significantly associated with reduced incidence of urinary incontinence (OR: 1.48; 95% CI: 1.10-1.98) and urinary retention compared to tamsulosin (OR: 3.39; 95% CI: 1.75-6.57 and tamsulosin/dutasteride (OR: 2.81; 95% CI: 1.35-5.82). Furthermore, significantly reduced the incidence of erectile dysfunction compared to dutasteride (OR: 2.79; 95% CI: 1.49-5.25). At the same time, patients receiving showed the same incidence of the remaining complications as those taking the reference substances. In conclusion, we observed a significant association between prescription and reduced incidence of urinary incontinence and urinary retention compared to tamsulosin and tamsulosin/dutasteride, as well as reduced incidence of erectile dysfunction compared to dutasteride.
Topics: Humans; Male; Prostatic Hyperplasia; Dutasteride; Tamsulosin; Retrospective Studies; Finasteride; 5-alpha Reductase Inhibitors; Erectile Dysfunction; Incidence; Urinary Retention; Treatment Outcome; Prescriptions; Urinary Incontinence; Drug Therapy, Combination
PubMed: 36408978
DOI: 10.1080/00325481.2022.2149156 -
Frontiers in Bioengineering and... 2022Androgenic alopecia (AGA) is a common disease that negatively affects patients' physical and mental health. AGA can be treated with drugs that improve the perifollicular...
Androgenic alopecia (AGA) is a common disease that negatively affects patients' physical and mental health. AGA can be treated with drugs that improve the perifollicular microenvironment, such as 5α-reductase inhibitors (e.g., dutasteride [DUT]), androgen receptor blockers, and minoxidil. However, the efficacy of these treatments is limited. Therefore, this study aimed to show that nanoparticles are effective as stable carriers with high curative benefits and little adverse effects. The study showed that PLGA-DUT/siAR@DPCM NPs could deliver both DUT and siAR to dermal papilla cells. They could successfully suppress 5α-reductase and knock down androgen receptor, respectively, and thereby promote cell proliferation. In the study, PLGA-DUT/siAR@DPCM NPs showed a significant therapeutic effect in an AGA mouse model. They successfully penetrated the stratum corneum and showed a clear targeting effect on hair follicles and surrounding tissues. PLGA-DUT/siAR@DPCM NPs could enable the targeted delivery of DUT and siAR through percutaneous penetration, enhancing phagocytosis and decreasing adverse effects. Thus, they have great potential in the clinical treatment of AGA.
PubMed: 36394031
DOI: 10.3389/fbioe.2022.1033987 -
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 -
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 -
Urologic Oncology Jan 2023The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. Our objective was to conduct a...
PURPOSE
The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. Our objective was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality.
PATIENTS AND METHODS
We used routinely collected health care data from Ontario, Canada. Men ≥66 years of age with a prescription for a 5ARI were matched to non-5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We measured 5 additional baseline variables which may have impacted the risk of future BC diagnosis: prior cystoscopy, urine cytology, urinalysis, gross hematuria episodes, and transurethral resection of a bladder lesion. Only the first period of continuous usage of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy and ended at the last date of 5ARI exposure + 1 year.
RESULTS
We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride) between 2003 and 2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (interquartile range 1.00, 4.27). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.82-1.32) during the period of 0 to <2 years of 5ARI use; however, after ≥2 years of 5ARI use, the risk of BC diagnosis was significantly lower among the 5ARI group (HR 0.82, 95% CI 0.79-0.94). In a similarly adjusted model, BC mortality was lower among 5ARI users, but no longer statistically significant (HR 0.82, 95% CI 0.65, 1.02). When stratified by type of 5ARI, finasteride significantly reduced the risk of BC diagnosis after ≥2 years of continuous use (HR 0.86, 95% CI 0.76, 0.96); however, dutasteride did not (HR 0.92, 95% CI 0.83, 1.03).
CONCLUSIONS
In a large cohort of men, the use of a 5ARI was associated with a significantly decreased the risk of BC diagnosis after more than 2 years of continuous therapy.
Topics: Male; Humans; 5-alpha Reductase Inhibitors; Dutasteride; Finasteride; Retrospective Studies; Urinary Bladder Neoplasms; Oxidoreductases; Ontario; Prostatic Hyperplasia
PubMed: 36319553
DOI: 10.1016/j.urolonc.2022.09.004 -
IET Nanobiotechnology Feb 2023Alopecia is a treatable disorder that usually occurs due to high levels of 5-alpha dihydrotestosterone in hair follicles. To enhance the storage capacity of hair...
Alopecia is a treatable disorder that usually occurs due to high levels of 5-alpha dihydrotestosterone in hair follicles. To enhance the storage capacity of hair follicles and alleviate the inherent characteristics of dutasteride, 5-alpha reductase inhibitor, a prolonged-release nanocarrier was synthesised, and its influence on rat abdomen's skin was investigated. Results showed the lower ratio of S/Co (higher ethanol concentration) increased the hydrodynamic nanocarriers' particle size due to thermodynamic disturbance and Ostwald ripening. In contrast, an increase in surfactant through a decrease in interfacial tension resulted in smaller nanocarriers of 32.4 nm. Moreover, an increase in viscosity had an inverse correlation with the nanoemulsions' particle size. Nanocarriers containing ethanol showed less entrapment efficacy, perhaps due to the rapid dissolution of dutasteride into ethanol during nanoemulsification, while, based on Stokes' equation, the addition of ethanol resulted in smaller particle size and stability of the system. Skin permeation analysis using Franz diffusion cells showed nanocarriers could pass through the skin and release dutasteride for 6 days. In conclusion, the optimum concentration of ingredients is decisive in guaranteeing the ideal particle size, stability, and skin permeation of nanocarriers. The Present dutasteride nanocarrier would promise a prolonged and sustained-release drug delivery system for Alopecia therapy.
Topics: Animals; Rats; Dutasteride; Hair Follicle; Cholestenone 5 alpha-Reductase; 5-alpha Reductase Inhibitors; Alopecia
PubMed: 36314605
DOI: 10.1049/nbt2.12101 -
Veterinary Sciences Sep 2022A 5-year-old recently castrated male Doberman dog presented for prolonged erection of one week's duration with associated pain and dysuria. This was the fourth episode...
A 5-year-old recently castrated male Doberman dog presented for prolonged erection of one week's duration with associated pain and dysuria. This was the fourth episode within a year. Each episode was associated with an unusual event, which was stressful for the dog. Castration performed two months prior to the final episode did not prevent recurrence. Due to tissue necrosis, penile amputation and urethrostomy had to be performed. The dog recovered fully. Prolonged erection that persists beyond or that is unrelated to sexual stimulation is called "priapism". This term refers to the Greek god Priapus, a god of fertility, memorialized in sculptures for his giant phallus. In humans, depending on the mechanism involved, priapism is classified as nonischemic or ischemic. Because prognosis and treatment are different, priapism must be determined to be nonischemic or ischemic. Nonischemic priapism is a rare condition observed when an increase in penile arterial blood flow overwhelms the capacity of venous drainage; it is often associated with penile trauma, and does not require medical intervention. Ischemic priapism is associated with decreased venous return. In humans, ischemic priapism accounts for 95% of cases, the majority of which are idiopathic. Ischemic priapism is a urological emergency; simple conservative measures such as aspiration of blood from the corpora cavernosa and intracavernosal injection of an adrenergic agent are often successful. Stuttering priapism, also called recurrent or intermittent priapism, is a particular form of ischemic priapism reported in humans that is characterized by repetitive episodes of prolonged erections. Management consists of treating each new episode as an episode of acute ischemic priapism, and preventing recurrence with oral medications such as dutasteride and/or baclofen, gabapentin, or tadalafil. To the authors' knowledge, this case is the first report of stuttering priapism in a dog.
PubMed: 36288131
DOI: 10.3390/vetsci9100518 -
Annals of Dermatology Oct 2022Dutasteride improves hair growth compared with finasteride in male androgenic alopecia (AGA) and is well tolerated. However, real-world evidence for long-term...
BACKGROUND
Dutasteride improves hair growth compared with finasteride in male androgenic alopecia (AGA) and is well tolerated. However, real-world evidence for long-term dutasteride use in AGA is lacking.
OBJECTIVE
To describe baseline characteristics, treatment patterns and long-term safety and effectiveness of dutasteride versus finasteride.
METHODS
This was a multicentre, retrospective medical chart review study conducted in South Korea. The index date was the first prescription of dutasteride or finasteride. Baseline characteristics were assessed 6 months prior to index. Safety and effectiveness (improvements in basic and specific [BASP] classification) data were collected from index throughout the observation period.
RESULTS
Overall, 600 male adult patients were included (dutasteride, n=295; finasteride, n=305). Dutasteride-treated patients were older (<0.001) and more likely to have moderate/severe BASP classification at baseline (=0.010) compared with finasteride-treated patients. Among patients treated with recommended, on-label dosing exclusively (n=535: dutasteride, n=250; finasteride, n=285), dutasteride-treated patients showed greater improvement in hair growth than finasteride-treated patients, as measured by the BASP basic M classification (adjusted incidence rate ratio [95% confidence interval]: 2.06 [1.08, 3.95]; =0.029). Among this same subset, overall occurrence of adverse events (AEs) during the observation period were not statistically equivalent between groups (dutasteride 7.6%, finasteride 10.5%; =0.201), although reports of AEs of special interest were equivalent (<0.001).
CONCLUSION
Dutasteride showed greater effectiveness than finasteride in improving BASP classification in treating male AGA and had a similar or possibly lower occurrence of overall AEs. Dutasteride may provide an effective and safe treatment option for male patients with AGA.
PubMed: 36198626
DOI: 10.5021/ad.22.027 -
American Journal of Clinical Dermatology Jan 2023Male androgenetic alopecia is a common condition and represents a major concern for patients who experience this condition. While there are different treatments to stop...
Male androgenetic alopecia is a common condition and represents a major concern for patients who experience this condition. While there are different treatments to stop hair loss and improve hair density, the 5-alpha reductase inhibitors have demonstrated to be effective in improving androgenetic alopecia in men and can maintain a positive response for many years. Oral finasteride 1 mg is a US FDA-approved option, but dutasteride 0.5 mg has been proven to induce better responses, especially in the frontal area. Both have been shown to be safe in clinical trials but there is widespread concern about sexual adverse effects among patients. The use of topical finasteride has increased during the last few years as a useful option to avoid systemic therapy. The efficacy of topical finasteride 0.25% daily has been demonstrated in clinical trials, with a less marked decrease in serum dihydrotestosterone levels than with oral intake. Mesotherapy with dutasteride has also become more widespread recently, although evidence of its effectiveness is limited to retrospective studies in real clinical practice. The use of oral minoxidil in androgenetic alopecia has not been approved by the FDA, however several clinical studies have shown that it is an effective treatment option. The initial dose recommended to treat male hair loss is 2.5 mg daily, although the dose is frequently increased to 5 mg daily. The main adverse effect of oral minoxidil is hypertrichosis, followed by dizziness or lower limb edema, which are much less common. Platelet-rich plasma is a non-pharmacological option to treat male androgenetic alopecia, with some clinical trials demonstrating an improvement in hair count after several months. Among the published studies, the main limitation to compare its efficacy is the heterogeneity of the procedure. The most frequent regimens propose treatment every 4 weeks for 3 months initially to assess the individual response. Another treatment alternative is the use of light devices with wavelengths of between 630 and 660 nm, known as low-level laser therapy. These devices can be used at home every day for 15-30 min. Their efficacy has been shown in a limited number of clinical trials; however, there is a lack of evidence about the efficacy of these devices compared with other medical options or as a complementary therapy in hair loss. The pipeline of potential new treatments for male androgenetic alopecia is strong. Pyrilutamide and GT20029 are being studied as topical antagonists of the androgen receptor, while cetirizine is another topical option with some initial promising results. Furthermore, according to isolated studies with heterogeneous treatment schemes, the use of botulinum toxin in the scalp might improve androgenetic alopecia, and lastly, scalp threading might increase the total hair count as growth factors are released during implantation.
Topics: Humans; Male; Alopecia; Dutasteride; Finasteride; Minoxidil; Retrospective Studies; Treatment Outcome
PubMed: 36169916
DOI: 10.1007/s40257-022-00730-y