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Sexual Medicine Oct 2022Erectile dysfunction (ED) is an adverse effect of many medications.
BACKGROUND
Erectile dysfunction (ED) is an adverse effect of many medications.
AIM
We used a national pharmacovigilance database to assess which medications had the highest reported frequency of ED.
METHODS
The Food and Drug Administration Adverse Event Reporting System (FAERS) was queried to identify medications with the highest frequency of ED adverse event reports from 2010 to 2020. Phosphodiesterase-5 inhibitors and testosterone were excluded because these medications are often used as treatments for men with ED. The 20 medications with the highest frequency of ED were included in the disproportionality analysis.
OUTCOMES
Proportional Reporting Ratios (PRRs) and their 95% confidence intervals were calculated.
RESULTS
The 20 medications accounted for 6,142 reports of ED. 5-α reductase inhibitors (5-ARIs) and neuropsychiatric medications accounted for 2,823 (46%) and 2,442 (40%) of these reports respectively. Seven medications showed significant levels of disproportionate reporting with finasteride and dutasteride having the highest PRRs: 110.03 (103.14-117.39) and 9.40 (7.83-11.05) respectively. The other medications are used in a wide variety of medical fields such as cardiology, dermatology, and immunology.
CLINICAL IMPLICATIONS
Physicians should be familiar with these medications and understand their respective mechanisms of action, so that they may counsel patients appropriately and improve their quality of life.
STRENGTHS AND LIMITATIONS
The strength of the study is its large sample size and that it captures pharmacologic trends on a national level. Quantitative and comparative "real-world" data is lacking for the most common medications associated with ED. The limitation is that the number of reported events does not establish causality and cannot be used to calculate ED incidence rates.
CONCLUSION
In a national pharmacovigilance database, 5-ARIs and neuropsychiatric medications had the highest reports of ED adverse effects. There were many other medications used in a variety of medical fields that were also associated with ED. Kaplan-Marans E, Sandozi A, Martinez M, et al. Medications Most Commonly Associated With Erectile Dysfunction: Evaluation of the Food and Drug Administration National Pharmacovigilance Database. Sex Med 2022;10:100543.
PubMed: 35843193
DOI: 10.1016/j.esxm.2022.100543 -
Journal of AOAC International Oct 2022Tamsulosin (TAM) and dutasteride (DUT) are ranked among the most frequently prescribed therapies in urology. Interestingly, studies have also been carried out on TAM/DUT...
BACKGROUND
Tamsulosin (TAM) and dutasteride (DUT) are ranked among the most frequently prescribed therapies in urology. Interestingly, studies have also been carried out on TAM/DUT in terms of their ability to protect against recent COVID-19. However, very few studies were reported for their simultaneous quantification in their combined dosage form and were mainly based on chromatographic analysis. Subsequently, it is very important to offer a simple, selective, sensitive, and rapid method for the quantification of TAM and DUT in their challenging dosage form.
OBJECTIVE
In this study, a new chemometrically assisted ultraviolet (UV) spectrophotometric method has been presented for the quantification of TAM and DUT without any prior separation.
METHOD
For the calibration set, a partial factorial experimental design was used, resulting in 25 mixtures with central levels of 20 and 25 μg/mL for TAM and DUT, respectively. In addition, to assess the predictive ability of the developed approaches, another central composite design of 13 samples was used as a validation set. Post-processing by chemometric analysis of the recorded zero-order UV spectra of these sets has been applied. These chemometric approaches include partial least-squares (PLS) and genetic algorithm (GA), as an effective variable selection technique, coupled with PLS.
RESULTS
The models' validation criteria displayed excellent recoveries and lower errors of prediction.
CONCLUSIONS
The proposed models were effectively used to determine TAM/DUT in their combined dosage form, and statistical comparison with the reported method revealed satisfactory results.
HIGHLIGHTS
Overall, this work presents powerful simple, selective, sensitive, and precise methods for simultaneous quantification of TAM/DUT in their dosage form with satisfactory results. The predictive ability and accuracy of the developed methods offer the opportunity to be employed as a quality control technique for the routine analysis of TAM/DUT when chromatographic instruments are not available.
Topics: Humans; Dutasteride; Tamsulosin; Research Design; COVID-19; Spectrophotometry, Ultraviolet; Least-Squares Analysis; Calibration; Pharmaceutical Preparations; Spectrophotometry
PubMed: 35758559
DOI: 10.1093/jaoacint/qsac080 -
Plants (Basel, Switzerland) Jun 2022In Thai folklore wisdom, shallot ( L.) was applied as a traditional herbal medicine for hair growth promotion with no scientific evidence. Androgenetic alopecia (AGA) is...
In Thai folklore wisdom, shallot ( L.) was applied as a traditional herbal medicine for hair growth promotion with no scientific evidence. Androgenetic alopecia (AGA) is a progressive hair loss caused by multiple factors, including androgen hormones, inflammation, and oxidative stress. Conventional medicines (finasteride, dutasteride, corticosteroids, and minoxidil) have been used with limited therapeutic efficacy and unpleasant side effects. In this study, we aimed to give the first estimation of bioactive compounds in shallot extract and evaluate the hair growth-promoting activities regarding anti-inflammatory and gene expression modulation involving androgen, Wnt/β-catenin, sonic hedgehog, and angiogenesis pathways. The results reveal that phenolic compounds (quercetin, rosmarinic, and -coumaric acids) are the major constituents of the methanolic shallot extract. Compared with the lipopolysaccharide-stimulated control group (2.68 ± 0.13 µM), nitric oxide production was remarkably diminished by shallot extract (0.55 ± 0.06 µM). Shallot extract improves hair growth promotion activity, as reflected by the downregulation of the androgen gene expression ( and and the upregulation of the genes associated with Wnt/β-catenin (), sonic hedgehog (, , and ), and angiogenesis () pathways. These findings disclose the new insights of shallot extract on hair growth promotions. Shallot extract could be further developed as nutraceutical, nutricosmetic, and cosmeceutical preparations for AGA treatment.
PubMed: 35684272
DOI: 10.3390/plants11111499 -
JAMA Oncology Jul 2022There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of...
IMPORTANCE
There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM).
OBJECTIVE
To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa.
DESIGN, SETTING, AND PARTICIPANTS
This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021.
EXPOSURES
After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190).
MAIN OUTCOMES AND MEASURES
Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM.
RESULTS
The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively).
CONCLUSIONS AND RELEVANCE
The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.
Topics: 5-alpha Reductase Inhibitors; Aged; Cohort Studies; Humans; Male; Middle Aged; Oxidoreductases; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Sweden
PubMed: 35587340
DOI: 10.1001/jamaoncol.2022.1501 -
Faculty Reviews 2022Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders of the luteal phase of the menstrual cycle and are characterized by moderate... (Review)
Review
Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders of the luteal phase of the menstrual cycle and are characterized by moderate to severe physical, affective, or behavioral symptoms that impair daily activities and quality of life. PMS and PMDD have recently raised great interest in the research community for their considerable global prevalence. The etiology of PMS/PMDD is complex. Ovarian reproductive steroids (estradiol and progesterone) are considered pathogenetic effectors, but the key feature seems to be an altered sensitivity of the GABAergic central inhibitory system to allopregnanolone, a neurosteroid derived from progesterone produced after ovulation. Also, a reduced availability of serotonin seems to be involved. New insights point to a role for genetic and epigenetic modifications of hormonal and neurotransmitter pathways, and inflammation is the potential link between peripheral and neurological integrated responses to stressors. Thus, new therapeutic approaches to PMS/PMDD include inhibition of progesterone receptors in the brain (i.e., with ulipristal acetate), reduced conversion of progesterone to its metabolite allopregnanolone with dutasteride, and possible modulation of the action of allopregnanolone on the brain GABAergic system with sepranolone. Further research is needed to better understand the interaction between peripheral inflammatory molecules (cytokines, interleukins, C-reactive protein, and reactive oxygen species) and the brain neurotransmitter systems in women with PMS/PMDD. If confirmed, neuroinflammation could lead both to develop targeted anti-inflammatory therapies and to define prevention strategies for the associated chronic inflammatory risk in PMS/PMDD. Finally, the observed association between premenstrual disorders and psychological diseases may guide prompt and adequate interventions to achieve a better quality of life.
PubMed: 35574174
DOI: 10.12703/r/11-11 -
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 -
Pharmaceutics Jan 2022Androgenetic alopecia is a multifactorial condition characterized by noticeable hair loss, affecting both men and women and representing a debilitating and chronic... (Review)
Review
Androgenetic alopecia is a multifactorial condition characterized by noticeable hair loss, affecting both men and women and representing a debilitating and chronic disorder that considerably affects the quality of life. Available topical treatments based on minoxidil or finasteride require repeated applications and are associated with a certain number of adverse effects. The challenges associated with current treatments pave the way for the research of new therapeutic strategies, more precise and selective, and capable of providing long-term results. In this context, the present review examines the new proposed formulation strategies to deliver 5-α-reductase inhibitors in order to obtain a targeted drug delivery, for improving drug retention at the site of action in the hair follicle, contemporaneously reducing drug systemic absorption, which is the cause of important adverse effects. In particular, the research will be focused on the several aspects that influence the performance of nanostructured drug delivery systems in creating a depot in the hair follicles, such as particle size, surface charge, excipients, and combined application with external stimuli (infrared radiation, mechanical massage, ultrasounds application).
PubMed: 35214018
DOI: 10.3390/pharmaceutics14020286 -
Asian Journal of Urology Jan 2022To evaluate the efficacy and safety of simultaneous administration of dutasteride, tadalafil and solifenacin in the treatment of benign prostatic hyperplasia (BPH) with...
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 (=97) received dutasteride 0.5 mg/day, tadalafil 2.5 mg/day, and solifenacin 2.5 mg/day; Group B (=95) received dutasteride 0.5 mg/day, tadalafil 5 mg/day, and solifenacin 5 mg/day; Group C (=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 80.2 points (>0.05) according to MSHQ-EjD, 61.4 points 51.2 points (>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 26.1 points, <0.05) and remained below the baseline until the end of the study (15.2 points).
CONCLUSIONS
The simultaneous administration of standard doses of dutasteride, solifenacin, and tadalafil for 3 months is safe, effective, and can be recommended for patients with BPH to reduce symptoms of obstruction and hyperactivity of the bladder and maintain sexual function.
PubMed: 35198395
DOI: 10.1016/j.ajur.2021.04.002 -
Asian Journal of Urology Jan 2022Bleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride...
The role of preoperative dutasteride in reducing bleeding during transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Bleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride before surgery could reduce perioperative bleeding. We aimed to evaluate the efficacy of preoperative dutasteride treatment in benign prostatic hyperplasia patients undergoing TURP by performing a meta-analysis of relevant randomized controlled trials (RCTs).
METHODS
A comprehensive literature search was performed through the electronic databases including Medline, Cochrane Library, Google Scholar, and ClinicalTrial.gov in October 2020. RCTs evaluating the role of dutasteride for TURP were screened using the eligibility criteria and the quality of RCTs was assessed using the Cochrane Risk of Bias Tool. The heterogeneity was assessed using statistic. The measured outcomes were hemoglobin (Hb) levels, perioperative blood loss, blood transfusion, microvessel density (MVD), and operation time. Data were pooled as mean difference (MD) and odds ratio (OR).
RESULTS
A total of 11 RCTs consisting of 627 samples from the treatment group and 615 samples from the placebo group were analyzed. Patients that received dutasteride had less reduction in Hb levels (MD -1.10, 95% confidence interval [CI] -1.39 to -0.81, <0.00001). Dutasteride also significantly reduced the operation time (MD -1.79, 95% CI -2.97 to -0.61, =0.003) and transfusion rate after surgery (OR 0.34, 95% CI 0.15 to 0.77, =0.009) compared to the control group. However, the MVD (MD -3.60, 95% CI -8.04 to 0.84, =0.11) and perioperative blood loss in dutasteride administration for less than 4 weeks (MD 46.90, 95% CI -144.60 to 238.41, =0.63) and more than 4 weeks (MD -190.13, 95% CI -378.05 to -2.21, =0.05) differences were insignificant.
CONCLUSION
Preoperative administration of dutasteride is able to reduce bleeding during TURP, as indicated by less reduction in Hb level, lower transfusion rate, and less operation time.
PubMed: 35198393
DOI: 10.1016/j.ajur.2021.05.011 -
Skin Appendage Disorders Jan 2022Alopecia after mesotherapy with dutasteride is an extremely rare complication. Dutasteride is a second-generation 5a-reductase enzyme inhibitor that decreases serum...
Alopecia after mesotherapy with dutasteride is an extremely rare complication. Dutasteride is a second-generation 5a-reductase enzyme inhibitor that decreases serum dihydrotestosterone levels by 90%. It inhibits both type 1 and 2 enzymes, whereas finasteride inhibits only type 2. Mesotherapy with dutasteride is a novel treatment for hair fall which involves microinjection of the drug into the dermis with negligible systemic absorption. Frequent mild transitory side effects in the site of injection are described in medical literature, but few cases of secondary alopecia have been reported. This stands out given that mesotherapy is becoming such an increasingly common procedure with a great number of patients treated with this technique. We present 2 cases of patchy alopecia after mesotherapy with dutasteride in a male and a female with androgenetic alopecia. One of them developed skin atrophy on the affected areas without improvement at short term follow-up. These cases highlight the possible paradoxical side effects of mesotherapy as a therapeutic technique for hair loss.
PubMed: 35118130
DOI: 10.1159/000518043