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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 -
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 -
Biomedicines Aug 2022Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the loss of upper and lower motor neurons (MNs) in the cerebral cortex,... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the loss of upper and lower motor neurons (MNs) in the cerebral cortex, brainstem and spinal cord, with consequent weakness, atrophy and the progressive paralysis of all muscles. There is currently no medical cure, and riluzole and edaravone are the only two known approved drugs for treating this condition. However, they have limited efficacy, and hence there is a need to find new molecules. Dutasteride, a dual inhibitor of type 1 and type 2 5α-reductase (5AR) enzymes, the therapeutic purposes of which, to date, are the treatment of benign prostatic hyperplasia and androgenic alopecia, shows great anti-ALS properties by the molecular-topology methodology. Based on this evidence, this review aims to assess the effects of dutasteride on testosterone (T), progesterone (PROG) and 17β-estradiol (17BE) as a therapeutic alternative for the clinical improvement of ALS, based on the hormonal, metabolic and molecular pathways related to the pathogenesis of the disease. According to the evidence found, dutasteride shows great neuroprotective, antioxidant and anti-inflammatory effects. It also appears effective against glutamate toxicity, and it is capable of restoring altered dopamine activity (DA). These effects are achieved both directly and through steroid hormones. Therefore, dutasteride seems to be a promising molecule for the treatment of ALS, although clinical studies are required for confirmation.
PubMed: 36140184
DOI: 10.3390/biomedicines10092084 -
Turkish Journal of Medical Sciences Dec 2021Currently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning of the pandemic, and many of... (Review)
Review
BACKGROUND/AIM
Currently there is not an effective antiviral treatment for COVID-19, but a large number of drugs have been evaluated since the beginning of the pandemic, and many of them have been used for the treatment of COVID-19 despite the preliminary or conflicting results of the clinical trials. We aimed to review and summarize all of the current knowledge on the antivirals for COVID-19
RESULTS
There are 2 main drug groups for SARS-CoV-2: agents that target proteins or RNA of the virus or interfere with proteins or biological processes in the host that support the virus. The main drug groups include inhibitors of viral entry into the human cell (convalescent plasma, monoclonal antibodies, nanobodies, mini proteins, human soluble ACE-2, camostat, dutasteride, proxalutamide, bromhexin, hydroxychloroquine, umifenovir nitazoxanid, niclosamide, lactoferrin), inhibitors of viral proteases (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376), inhibitors of viral RNA (remdesivir, favipiravir, molnupiravir, AT-527, merimepodib, PTC299), inhibitors of host proteins supporting virus (plitidepsin, fluvoxamine, ivermectin), and agents supporting host natural immunity (Interferons).
CONCLUSION
When taking into account the results of all the available laboratory and clinical trials on the subject, monoclonal antibodies seem to be the most effective treatment for COVID-19 at the moment, and high-titer convalescent plasma also could be effective when administered during the early phase of the disease. As lopinavir/ritonavir, hydroxychloroquine, merimepodib, and umifenovir were found to be ineffective in RCTs, they should not be used. Additional studies are needed to define the role of remdesivir, favipiravir, interferons, ivermectin, dutasteride, proxulutamide, fluvoxamine, bromhexine, nitazoxanide, and niclosamid in the treatment of COVID-19. Finally, the results of phase trials are waited to learn whether or not the newer agents such as molnupiravir, PF-07321332, PF-07304814, plitidepsin and AT-527 are effective in the treatment of COVID-19.
Topics: Antiviral Agents; COVID-19; Humans; Immunization, Passive; Pandemics; SARS-CoV-2; COVID-19 Serotherapy; COVID-19 Drug Treatment
PubMed: 34391321
DOI: 10.3906/sag-2106-250 -
Asian Journal of Andrology 2020Androgen deprivation therapy (ADT) is the mainstay for the treatment of advanced prostate cancer. Since the clinical evolution from surgical orchiectomy, we have... (Review)
Review
Androgen deprivation therapy (ADT) is the mainstay for the treatment of advanced prostate cancer. Since the clinical evolution from surgical orchiectomy, we have typically used ADT and orchiectomy to be synonymous terms for castration. The goal of this study is to determine if, in contemporary medical practice, surgical and chemical castration provide for similar levels of diminishment of total and free testosterone. Further, what approaches should be used to most accurately measure testosterone levels in men with advanced prostate cancer and what cutoff values, for example for total testosterone 50 ng dl or 20 ng dl, should be utilized. Studies available in the literature have been analyzed and compiled to address these questions. Finally, evidence is provided that free testosterone, the biologically active component, should be utilized to provide clinically relevant state of castration.
Topics: Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Chromatography, Liquid; Combined Modality Therapy; Dutasteride; Finasteride; Gonadotropin-Releasing Hormone; Humans; Luminescence; Male; Mass Spectrometry; Orchiectomy; Practice Guidelines as Topic; Prostatic Neoplasms; Radioimmunoassay; Steroid 17-alpha-Hydroxylase; Testosterone
PubMed: 31997782
DOI: 10.4103/aja.aja_139_19 -
International Braz J Urol : Official... 2023To evaluate the penile morphology after the isolated and combined administration of dutasteride and tamsulosin in a rodent model.
PURPOSE
To evaluate the penile morphology after the isolated and combined administration of dutasteride and tamsulosin in a rodent model.
MATERIALS AND METHODS
Forty male rats were assigned into the following groups: Control group (C, receiving distilled water, n=10); Dutasteride group (D, receiving 0.5 mg/Kg/day of dutasteride, n=10); Tamsulosin group (T, receiving 0.4 mg/Kg/day of tamsulosin, n=10); and Dutasteride associated with Tamsulosin group (DT, receiving both drugs n = 10). All drugs were administered via oral gavage. After 40 days, the animals were submitted to euthanasia and their penises were collected for histomorphometric analyses. Data were compared using one-way ANOVA followed by Bonferroni's post-test, considering p<0.05 as significant.
RESULTS
The sinusoidal space and smooth muscle fiber surface densities (Sv), and the cross-sectional penile areas of rats in groups D, T and DT were reduced in comparison to controls with the most notable reductions in the combined therapy group. The connective tissue and elastic system fibers Sv were augmented in groups D, T and DT in comparison with the control group, again with the most pronounced changes observed in animals receiving the combined therapy.
CONCLUSION
Both treatments with dutasteride or tamsulosin promoted penile morphometric modifications in a rodent model. The combination therapy resulted in more notable modifications. The results of this study may help to explain the erectile dysfunction observed in some men using these drugs.
Topics: Humans; Male; Rats; Animals; Dutasteride; Tamsulosin; 5-alpha Reductase Inhibitors; Prostatic Hyperplasia; Rodentia; Cross-Sectional Studies; Drug Therapy, Combination
PubMed: 37115177
DOI: 10.1590/S1677-5538.IBJU.2022.0583 -
The Lancet Regional Health. Europe Aug 2023Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms...
Prostatic artery embolisation versus medical treatment in patients with benign prostatic hyperplasia (PARTEM): a randomised, multicentre, open-label, phase 3, superiority trial.
BACKGROUND
Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms improvement after PAE and medical treatment.
METHODS
A randomised, open-label, superiority trial was set in 10 French hospitals. Patients with bothersome lower urinary tract symptoms (LUTS) defined by International Prostatic Symptom Score (IPSS) > 11 and quality of life (QoL) > 3, and BPH ≥50 ml resistant to alpha-blocker monotherapy were randomly assigned (1:1) to PAE or Combined Therapy ([CT], oral dutasteride 0.5 mg/tamsulosin hydrochloride 0.4 mg per day). Randomisation was stratified by centre, IPSS and prostate volume with a minimisation procedure. The primary outcome was the 9-month IPSS change. Primary and safety analysis were done according to the intention-to-treat (ITT) principle among patients with an evaluable primary outcome. ClinicalTrials.gov Identifier: NCT02869971.
FINDINGS
Ninety patients were randomised from September 2016 to February 2020, and 44 and 43 patients assessed for primary endpoint in PAE and CT groups, respectively. The 9-month change of IPSS was -10.0 (95% confidence interval [CI]: -11.8 to -8.3) and -5.7 (95% CI: -7.5 to -3.8) in the PAE and CT groups, respectively. This reduction was significantly greater in the PAE group than in the CT group (-4.4 [95% CI: -6.9 to -1.9], p = 0.0008). The IIEF-15 score change was 8.2 (95% CI: 2.9-13.5) and -2.8 (95% CI: -8.4 to 2.8) in the PAE and CT groups, respectively. No treatment-related AE or hospitalisation was noticed. After 9 months, 5 and 18 patients had invasive prostate re-treatment in the PAE and CT group, respectively.
INTERPRETATION
In patients with BPH ≥50 ml and bothersome LUTS resistant to alpha-blocker monotherapy, PAE provides more urinary and sexual symptoms benefit than CT up to 24 months.
FUNDING
French Ministry of Health and a complementary grant from Merit Medical.
PubMed: 37415648
DOI: 10.1016/j.lanepe.2023.100672 -
Biomedicines Feb 2024Hair loss is a common clinical condition connected with serious psychological distress and reduced quality of life. Hormones play an essential role in the regulation of... (Review)
Review
Hair loss is a common clinical condition connected with serious psychological distress and reduced quality of life. Hormones play an essential role in the regulation of the hair growth cycle. This review focuses on the hormonal background of hair loss, including pathophysiology, underlying endocrine disorders, and possible treatment options for alopecia. In particular, the role of androgens, including dihydrotestosterone (DHT), testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA), and its sulfate (DHEAS), has been studied in the context of androgenetic alopecia. Androgen excess may cause miniaturization of hair follicles (HFs) in the scalp. Moreover, hair loss may occur in the case of estrogen deficiency, appearing naturally during menopause. Also, thyroid hormones and thyroid dysfunctions are linked with the most common types of alopecia, including telogen effluvium (TE), alopecia areata (AA), and androgenetic alopecia. Particular emphasis is placed on the role of the hypothalamic-pituitary-adrenal axis hormones (corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol) in stress-induced alopecia. This article also briefly discusses hormonal therapies, including 5-alpha-reductase inhibitors (finasteride, dutasteride), spironolactone, bicalutamide, estrogens, and others.
PubMed: 38540126
DOI: 10.3390/biomedicines12030513 -
Frontiers in Pharmacology 2022Gastrointestinal disorders in Parkinson's disease (PD) have been associated with neuronal alteration in the plexus of the gut. We previously demonstrated the...
Gastrointestinal disorders in Parkinson's disease (PD) have been associated with neuronal alteration in the plexus of the gut. We previously demonstrated the immunomodulatory effect of female hormones to treat enteric neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. This study made the hypothesis of obtaining similar neuroprotection as with hormone treatments by affecting steroidogenesis with two 5α-reductase inhibitors, finasteride and dutasteride. These drugs are approved to treat benign prostatic hyperplasia and alopecia and display mitochondrial effects. In MPTP-treated mice, the dopaminergic and vasoactive intestinal peptide (VIP) neurons alteration was prevented by finasteride and dutasteride, while the increase in proinflammatory macrophages density was inhibited by dutasteride treatment but not finasteride. NF-κB response, oxidative stress, and nitric oxide and proinflammatory cytokines production were only prevented by dutasteride. In addition, mitochondrial production of free radicals, membrane depolarization, decreased basal respiration, and ATP production were inhibited by dutasteride, while finasteride had no effect. In conclusion, the present results indicate that dutasteride treatment prevents enteric neuronal damages in the MPTP mouse model, at least in part through anti-inflammatory and mitochondrial effects. This suggests that drug repurposing of dutasteride might be a promising avenue to treat enteric neuroinflammation in early PD.
PubMed: 35935876
DOI: 10.3389/fphar.2022.898067 -
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