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Translational Andrology and Urology Feb 2020The objective of this study is to review our 12-year experience with the 5-α reductase inhibitor dutasteride as a potential long-term treatment option for stuttering...
BACKGROUND
The objective of this study is to review our 12-year experience with the 5-α reductase inhibitor dutasteride as a potential long-term treatment option for stuttering priapism. Dutasteride has a uniquely long half-life of 35 days which offers a theoretical advantage as a chronic therapy for management of stuttering priapism.
METHODS
We retrospectively reviewed patients with stuttering priapism in our database from 2006-2018 treated with dutasteride. Men with concurrent use of medications other than dutasteride to treat stuttering priapism were excluded. Patients were started on a dose of 0.5 mg daily and tapered to a more infrequent dosing schedule, ranging from 0.5 mg every other day to once weekly. The frequency of priapism episodes before and after initiation of dutasteride therapy was analyzed.
RESULTS
Among 21 cases, 13 patients met our inclusion criteria (mean age 43 years). Median follow-up on daily dutasteride was 79 days, and median follow-up on tapered dutasteride was 607 days. A total of 11/13 (85%) men treated with dutasteride had some degree of improvement-5/13 (38%) had complete resolution of their symptoms and 6/13 (46%) had reduced frequency and/or severity of their episodes. Among 5/13 (38%) men who had >2 emergency room (ER) visits for ischemic priapism prior to therapy, most (3/5, 60%) did not require any ER visits while on dutasteride therapy. Among the five men who received chronic, tapered-dose therapy, all reported continued suppression of priapistic episodes. Among 4 patients with sickle cell disease (SCD), 3/4 (75%) ultimately chose more invasive therapy including androgen deprivation therapy (ADT) and penile prosthesis. Side effects were minimal and included gynecomastia (8%), decreased libido (8%), and fatigue (8%).
CONCLUSIONS
In patients with stuttering priapism, daily dutasteride therapy is a promising treatment option to reduce the frequency and severity of priapistic episodes without significant side effects. Therapy can effectively be tapered to once weekly dosing without a reduction in efficacy.
PubMed: 32055472
DOI: 10.21037/tau.2019.07.15 -
BioMed Research International 2016This study aimed to assess the efficacy of combination therapy with dutasteride and silodosin in patients with acute urinary retention (AUR) caused by benign prostatic... (Clinical Trial)
Clinical Trial
This study aimed to assess the efficacy of combination therapy with dutasteride and silodosin in patients with acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH). Eighty consecutive patients with a first episode of AUR were enrolled in this study. All patients received silodosin 8 mg and dutasteride 0.5 mg daily. Trial without catheter (TWOC) was attempted every 2 weeks until 12 weeks after the initiation of medication. The primary endpoint was the rate of catheter-free status at 12 weeks. Voided volume (VV), postvoid residual urine (PVR), uroflowmetry, International Prostatic Symptoms Score (IPSS), and quality of life due to urinary symptoms (IPSS-QOL) were also measured. All patients were followed up for more than 12 weeks and were included in this analysis. The success rate of TWOC at 12 weeks was 88.8%. VV and maximum urinary flow rate were significantly higher at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). IPSS and IPSS-QOL were significantly lower at 2, 4, 8, and 12 weeks compared with the time of AUR (P < 0.001). In conclusion, a combination of dutasteride and silodosin therapy may be effective and safe for patients with AUR due to BPH.
Topics: Acute Disease; Aged; Aged, 80 and over; Drug Therapy, Combination; Dutasteride; Humans; Indoles; Kaplan-Meier Estimate; Male; Prospective Studies; Prostatic Hyperplasia; Time Factors; Treatment Outcome; Urinary Retention; Urination
PubMed: 27195288
DOI: 10.1155/2016/4975851 -
Asian Journal of Urology Jan 2019Prostate cancer (PCa) growth and progression rely on the interaction between the androgen receptor (AR) and the testicular ligands, testosterone and dihydrotestosterone... (Review)
Review
Prostate cancer (PCa) growth and progression rely on the interaction between the androgen receptor (AR) and the testicular ligands, testosterone and dihydrotestosterone (DHT). Almost all men with advanced PCa receive androgen deprivation therapy (ADT). ADT lowers circulating testosterone levels, which impairs AR activation and leads to PCa regression. However, ADT is palliative and PCa recurs as castration-recurrent/resistant PCa (CRPC). One mechanism for PCa recurrence relies on intratumoral synthesis of DHT, which can be synthesized using the frontdoor or primary or secondary backdoor pathway. Androgen metabolism inhibitors, such as those targeting 5α-reductase, aldo-keto-reductase family member 3 (AKR1C3), or cytochrome P450 17A1 (CYP17A1) have either failed or produced only modest clinical outcomes. The goal of this review is to describe the therapeutic potential of combined inhibition of 5α-reductase and 3α-oxidoreductase enzymes that facilitate the terminal steps of the frontdoor and primary and secondary backdoor pathways for DHT synthesis. Inhibition of the terminal steps of the androgen metabolism pathways may be a way to overcome the shortcomings of existing androgen metabolism inhibitors and thereby delay PCa recurrence during ADT or enhance the response of CRPC to androgen axis manipulation.
PubMed: 30775248
DOI: 10.1016/j.ajur.2018.09.002 -
Pharmaceutics Sep 2022Lower Urinary Tract Symptoms (LUTs) in men are usually associated to benign prostatic hyperplasia (BPH), a non-malignant prostate enlargement. Unfortunately, BPH...
Lower Urinary Tract Symptoms (LUTs) in men are usually associated to benign prostatic hyperplasia (BPH), a non-malignant prostate enlargement. Unfortunately, BPH etiology is still unclear. Recent works highlighted a relevant inflammation role in BPH onset and development. Consequently, to complement the 5-α reductase (and α-adrenergic receptor agonists-based therapy, an anti-inflammatory therapy should be devised. To reduce potential adverse effects of multi-drug treatment, plant extract-based therapies are becoming increasingly common. Serenoa repens, the main phytotherapic treatment for BPH, is not sufficient to front the multi-faceted etiology of BPH. In response to this, a novel, multiple phytotherapic agents-based formulation, LENILUTS, was developed. In the present work, we compared, using an in vitro approach, the prostatic safety and efficacy of LENILUTS with a commercial formulation, based only on Serenoa repens, and a 5αR inhibitor, Dutasteride. Furthermore, preliminary in vitro experiments to investigate the active principles, bioaccessibility and bioavailability of LENILUTS were performed. Our results showed a better prostatic safety and therapeutic efficacy of LENILUTS compared to the commercial formulation and Dutasteride, with increased anti-inflammatory, and pro-apoptotic activity, and a stronger inhibitory effect on the release of the key enzyme 5αR and Prostatic-Specific Antigen (PSA). The limited bioaccessibility and bioavailability of the active principles of LENILUTS were highlighted. Considering the results obtained, the LENILUTS formulation is more promising for BPH and LUTs therapy compared to formulations based on Serenoa repens only, but further efforts should be made to improve the bioaccessibility and bioavailability of the active principles.
PubMed: 36145614
DOI: 10.3390/pharmaceutics14091866 -
American Family Physician Jul 2002Medical and surgical options for the treatment of benign prostatic hyperplasia have expanded in recent years. Saw palmetto, the most widely used complementary... (Review)
Review
Medical and surgical options for the treatment of benign prostatic hyperplasia have expanded in recent years. Saw palmetto, the most widely used complementary medication, is less effective than standard medical therapy but has fewer side effects. Although non-selective alpha blockers provide rapid relief of symptoms and are relatively inexpensive, they can cause dizziness and orthostatic hypotension. These effects occur less often with tamsulosin, a more selective alpha blocker. Finasteride, a 5alpha-reductase inhibitor, slowly reduces prostatic volume but is not as effective as alpha blockers, especially in men with a smaller prostate. Dutasteride, a new 5alpha-reductase inhibitor, has recently been labeled for the treatment of benign prostatic hyperplasia. Surgery may be appropriate initial treatment in patients with severe symptoms who are not at high risk for complications. Surgery may also be indicated in patients who have failed medical therapy or have recurrent infection, hematuria, or renal insufficiency. Transurethral resection of the prostate is effective in most patients, but it carries some risk of sexual dysfunction, incontinence, and bleeding. Surgical procedures that use thermal microwave or laser energy to reduce hyperplastic prostate tissue have recently become available. In general, the newer procedures are less expensive than transurethral resection of the prostate and have fewer complications; however, the need for retreatment is somewhat greater with these less invasive techniques.
Topics: Complementary Therapies; Doxazosin; Humans; Male; Palpation; Prostatectomy; Prostatic Hyperplasia; Severity of Illness Index; Sulfonamides; Tamsulosin; Transurethral Resection of Prostate; Urine
PubMed: 12126034
DOI: No ID Found -
Heliyon Jul 2017Previously, we studied the effect of finasteride- or dutasteride-containing diets in male C57BL/6 TRAMP x FVB mice. Pre (6 weeks of age) and post (12 weeks of age)...
BACKGROUND
Previously, we studied the effect of finasteride- or dutasteride-containing diets in male C57BL/6 TRAMP x FVB mice. Pre (6 weeks of age) and post (12 weeks of age) groups received finasteride or dutasteride to determine the efficacy of these pharmaceuticals on prostate cancer (PCa) development in male C57BL/6 TRAMP x FVB mice. Post-Dutasteride treatment was more effective than Pre-Dutasteride treatment, and dutasteride treatments were more effective than finasteride treatments in decreasing prostatic intraepithelial neoplasia (PIN) progression and PCa development. Finasteride and Pre-Dutasteride treatments significantly decreased high-grade PIN incidence, but increased poorly differentiated PCa incidence. In this study, molecular changes in prostates of these mice were characterized in an effort to elucidate the discordant response in Pre-Dutasteride and finasteride groups, and determine why Post-Dutasteride treatment was more effective.
METHOD/PRINCIPAL FINDINGS
Ki-67 (proliferation marker) and androgen receptor (AR) protein, apoptotic DNA fragmentation (TUNEL assay), 5α-reductase 1 (5αR1) and 5α-reductase 2 (5αR2) mRNA were quantified in male TRAMP mice prostate tissues with genitourinary weight < 1 and > 1 gram. Overall, proliferation and AR were decreased and apoptosis was increased in most tumors versus prostate epithelium and hyperplasia. Proliferation and AR were increased notably in hyperplasia versus prostate epithelium and tumor. There were no clear trends or differences in 5α-reductase 1 and 5α-reductase 2 levels between large and small tumors. The discordant response in Pre-Finasteride and Pre-Dutasteride groups may be due to upregulated 5αR1 levels in large versus small tumors. It is not clear what the mechanism is for the different response in the Post-Finasteride group. Post-Dutasteride treatment was more effective than Pre-Dutasteride treatment in decreasing 5αR1 in large tumors. Therefore, this may be why this treatment was more effective in decreasing PIN progression and PCa development.
CONCLUSION
The effect of finasteride and dutasteride on these biomarkers did not clearly elucidate their mechanism of action, but tumor 5αR1 levels were significantly positively correlated with adjusted prostate severe lesion score.
PubMed: 28765837
DOI: 10.1016/j.heliyon.2017.e00360 -
Asian Journal of Andrology Nov 20115α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies... (Review)
Review
5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials (RCTs) and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density (MVD) in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-quality prospective studies are still needed to confirm this observation.
Topics: 5-alpha Reductase Inhibitors; Azasteroids; Blood Loss, Surgical; Dutasteride; Finasteride; Humans; Male; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 21892196
DOI: 10.1038/aja.2011.86 -
Indian Journal of Dermatology,... 2014The effectiveness of finasteride and dutasteride in women with androgenetic alopecia has been the subject of debate.
BACKGROUND
The effectiveness of finasteride and dutasteride in women with androgenetic alopecia has been the subject of debate.
AIM
To evaluate the effectiveness of finasteride and dutasteride on hair loss in women with androgenetic alopecia over a period of 3 years.
METHODS
From a database containing systematically retrieved data on 3500 women treated for androgenetic alopecia between 2002 and 2012 with finasteride 1.25 mg or dutasteride 0.15 mg, a random sample stratified for age and type of medication was taken to yield 30 women in two age categories: below and above 50 years, and for both medications. Hair thickness of the three thinnest hairs was measured from standardized microscopic images at three sites of the scalp at the start of the treatment and after 3 years of continuous medication intake. The macroscopic images were evaluated independently by three European dermatologists/hair experts. The diagnostic task was to identify the image displaying superior density of the hair.
RESULTS
Both age categories showed a statistically significant increase in hair thickness from baseline over the 3-year period for finasteride and dutasteride (signed rank test, P=0.02). Hair thickness increase was observed in 49 (81.7%) women in the finasteride group and in 50 (83.3%) women in the dutasteride group. On average, the number of post-treatment images rated as displaying superior density was 124 (68.9%) in the finasteride group, and 118 (65.6%) in the dutasteride group. Dutasteride performed statistically significantly better than finasteride in the age category below 50 years at the central and vertex sites of the scalp.
CONCLUSIONS
Finasteride 1.25 mg and dutasteride 0.15 mg given daily for 3 years effectively increased hair thickness and arrested further deterioration in women with androgenetic alopecia.
Topics: 5-alpha Reductase Inhibitors; Alopecia; Dutasteride; Female; Finasteride; Hair; Humans; Microscopy; Middle Aged; Photography; Retrospective Studies; Scalp
PubMed: 25382509
DOI: 10.4103/0378-6323.144162 -
The Journal of Clinical Endocrinology... Aug 20145α-Reductase (5αR) types 1 and 2 catalyze the A-ring reduction of steroids, including androgens and glucocorticoids. 5α-R inhibitors lower dihydrotestosterone in... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
5α-Reductase (5αR) types 1 and 2 catalyze the A-ring reduction of steroids, including androgens and glucocorticoids. 5α-R inhibitors lower dihydrotestosterone in benign prostatic hyperplasia; finasteride inhibits 5αR2, and dutasteride inhibits both 5αR2 and 5αR1. In rodents, loss of 5αR1 promotes fatty liver.
OBJECTIVE
Our objective was to test the hypothesis that inhibition of 5αR1 causes metabolic dysfunction in humans.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind randomized controlled parallel group study at a clinical research facility included 46 men (20-85 years) studied before and after intervention.
INTERVENTION
Oral dutasteride (0.5 mg daily; n = 16), finasteride (5 mg daily; n = 16), or control (tamsulosin; 0.4 mg daily; n = 14) was administered for 3 months.
MAIN OUTCOME MEASURE
Glucose disposal was measured during a stepwise hyperinsulinemic-euglycemic clamp. Data are mean (SEM).
RESULTS
Dutasteride and finasteride had similar effects on steroid profiles, with reduced urinary androgen and glucocorticoid metabolites and reduced circulating DHT but no change in plasma or salivary cortisol. Dutasteride, but not finasteride, reduced stimulation of glucose disposal by high-dose insulin (dutasteride by -5.7 [3.2] μmol/kg fat-free mass/min, versus finasteride +7.2 [3.0], and tamsulosin +7.0 [2.0]). Dutasteride also reduced suppression of nonesterified fatty acids by insulin and increased body fat (by 1.6% [0.6%]). Glucose production and glycerol turnover were unchanged. Consistent with metabolic effects of dutasteride being mediated in peripheral tissues, mRNA for 5αR1 but not 5αR2 was detected in human adipose tissue.
CONCLUSION
Dual inhibition of 5αRs, but not inhibition of 5αR2 alone, modulates insulin sensitivity in human peripheral tissues rather than liver. This may have important implications for patients prescribed dutasteride for prostatic disease.
Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; 5-alpha Reductase Inhibitors; Adipose Tissue; Adult; Aged; Aged, 80 and over; Azasteroids; Blood Glucose; Body Composition; Double-Blind Method; Dutasteride; Finasteride; Humans; Insulin Resistance; Male; Middle Aged; Prostatic Hyperplasia; Young Adult
PubMed: 24823464
DOI: 10.1210/jc.2014-1395 -
BMC Endocrine Disorders Sep 2020Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a...
BACKGROUND
Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2.
MAIN TEXT
While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed.
CONCLUSION
While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.
Topics: Anti-Inflammatory Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Dexamethasone; Drug Repositioning; Endocrine System; Humans; Pandemics; Pneumonia, Viral; Prognosis; SARS-CoV-2
PubMed: 32993622
DOI: 10.1186/s12902-020-00626-0