-
European Urology Focus Apr 20245α-Reductase inhibitors (5-ARIs) are widely prescribed for treatment of benign prostatic obstruction and androgenic alopecia. Several studies with controversial... (Review)
Review
5α-Reductase inhibitors (5-ARIs) are widely prescribed for treatment of benign prostatic obstruction and androgenic alopecia. Several studies with controversial findings regarding 5-ARI exposure have been published over a number of years, and concerns were recently raised about the potential risks of depression and suicide associated with 5-ARIs. To investigate this association, we conducted a systematic review of the literature and a meta-analysis. Five studies involving 2213600 patients met our inclusion criteria. We found no statistically significant association between 5-ARI exposure and the risk of depression (adjusted hazard ratio [aHR] 1.30, 95% confidence interval [CI] 0.85-2.00; p = 0.23) or suicide (aHR 1.30, 95% CI 0.65-2.61; p = 0.45). Subgroup analyses for finasteride and dutasteride revealed similar results. When restricting the analysis to patients without a prior diagnosis of depression, we observed similar findings (aHR for suicide 1.00, 95% CI 0.68-1.46; p = 0.98). PATIENT SUMMARY: We reviewed study data for more than two million patients taking drugs called 5α-reductase inhibitors (5-ARIs), which are widely prescribed for urinary problems caused by benign prostate enlargement and for male-pattern hair loss. In a pooled analysis we found no evidence of an association between 5-ARI use and the risk of depression or suicide.
PubMed: 38692949
DOI: 10.1016/j.euf.2024.04.009 -
Journal of Clinical PsychopharmacologyPrior studies indicate that neuroactive steroids mediate some of alcohol's effects. Dutasteride, widely used to treat benign prostatic hypertrophy, is an inhibitor of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Prior studies indicate that neuroactive steroids mediate some of alcohol's effects. Dutasteride, widely used to treat benign prostatic hypertrophy, is an inhibitor of 5-alpha reductase enzymes, which play a central role in the production of 5α-reduced neuroactive steroids. The purpose of this study was to test dutasteride's tolerability and efficacy for reducing drinking.
METHODS
Men (n = 142) with heavy drinking (>24 drinks per week) and a goal to either stop or reduce drinking to nonhazardous levels were randomized to placebo or 1 mg dutasteride daily for 12 weeks. We hypothesized that dutasteride-treated patients would be more successful in reducing drinking.
RESULTS
Generalized linear mixed models that included baseline drinking, treatment, time and their 2-way interaction identified significant interactions of treatment-time, such that dutasteride treatment reduced drinking more than placebo. During the last month of treatment, 25% of dutasteride-treated participants had no hazardous drinking (no heavy drinking days and not more than 14 drinks per week) compared with 6% of placebo-treated participants (P = 0.006; NNT = 6). Sensitivity analysis identified baseline drinking to cope as a factor associated with larger reductions in drinking for dutasteride compared with placebo-treated participants. Dutasteride was well tolerated. Adverse events more common in the dutasteride group were stomach discomfort and reduced libido.
CONCLUSION
Dutasteride 1 mg daily was efficacious in reducing the number of heavy drinking days and drinks per week in treatment-seeking men. The benefit of dutasteride compared with placebo was greatest for participants with elevated baseline drinking to cope motives.
Topics: Humans; Dutasteride; Male; 5-alpha Reductase Inhibitors; Middle Aged; Alcohol Drinking; Adult; Double-Blind Method; Treatment Outcome; Aged; Azasteroids
PubMed: 38684046
DOI: 10.1097/JCP.0000000000001849 -
Expert Opinion on Emerging Drugs Apr 2024Androgenetic alopecia (AGA) is the most prevalent cause of male hair loss, often requiring medical and/or surgical intervention. The US FDA has approved topical... (Review)
Review
INTRODUCTION
Androgenetic alopecia (AGA) is the most prevalent cause of male hair loss, often requiring medical and/or surgical intervention. The US FDA has approved topical minoxidil and oral finasteride for male AGA treatment. However, some AGA patients fail to respond satisfactorily to these FDA-approved treatments and/or may experience side effects, based on their individual profiles. To mitigate the shortcomings of these treatments, researchers are now exploring alternative treatments such as newer 5-α reductase inhibitors (5-ARIs) and androgen receptor antagonists (ARAs).
AREAS COVERED
This article reviews the safety and effectiveness of well-known 5-α reductase inhibitors (5-ARIs) like finasteride and dutasteride, as well as the newer 5-ARIs, emerging androgen receptor antagonists (ARAs), and natural products such as saw palmetto and pumpkin seed oil in the treatment of male AGA.
EXPERT OPINION
Although several newer 5-ARIs, ARAs, and natural products have exhibited promise in clinical trials, additional research is essential to confirm their safety and efficacy in treating male AGA. Until additional evidence is available for these agents, the preferred treatment choices for male AGA are the FDA-approved treatments, topical minoxidil, and oral finasteride.
PubMed: 38666717
DOI: 10.1080/14728214.2024.2346590 -
Journal of Ethnopharmacology Aug 2024Benign prostatic hyperplasia (BPH), characterized by prostate enlargement due to cell proliferation, is a common urinary disorder in men over 50, manifesting as lower... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Benign prostatic hyperplasia (BPH), characterized by prostate enlargement due to cell proliferation, is a common urinary disorder in men over 50, manifesting as lower urinary tract symptoms (LUTS). Currently, several therapeutic options are accessible for treating BPH, including medication therapy, surgery and watchful waiting. Conventional drugs such as finasteride and dutasteride are used as 5α-reductase inhibitors for the treatment of BPH. However long-term use of these drugs is restricted due to their unpleasant side effects. Despite the range of available medical therapies, the effective treatment against BPH is still inadequate. Certain therapeutic plants and their phytochemicals have the aforementioned goals and work by regulating this enzyme.
AIM OF THE STUDY
This review aims to provide a comprehensive insight to advancements in diagnosis of BPH, modern treatment methods and the significance of ethnobotanically relevant medicinal plants as alternative therapeutics for managing BPH.
MATERIAL AND METHODS
A thorough and systematic literature search was performed using electronic databases and search engines such as PubMed, Web of Science, NCBI and SciFinder till October 2023. Specific keywords such as "benign prostatic hyperplasia", "medicinal plants", "phytochemicals", "pharmacology", "synergy", "ethnobotany", "5-alpha reductase", "alpha blocker" and "toxicology". By include these keywords, a thorough investigation of pertinent papers was assured, and important data about the many facets of BPH could be retrieved.
RESULTS
After conducting the above investigation, 104 herbal remedies were found to inhibit Phosphodiesterase-5 (PDE-5) inhibition, alpha-blockers, or 5α -reductase inhibition effects which are supported by in vitro, in vivo and clinical trial studies evidence. Of these, 89 plants have ethnobotanical significance as alpha-blockers, alpha-reductase inhibition, or PDE-5 inhibition, and the other fifteen plants were chosen based on their ability to reduce BPH risk factors. Several phytocompounds, including, rutaecarpine, vaccarin, rutin, kaempferol, β-sitosterol, quercetin, dicaffeoylquinic acid, rutaevin, and phytosterol-F have been reported to be useful for the management of BPH. The use of combination therapy offers a strong approach to treating long-term conditions compare to single plant extract drugs. Furthermore, several botanical combinations such as lycopene and curcumin, pumpkin seed oil and saw palmetto oil, combinations of extracts from Funtumia africana (Benth.) Stapf and Abutilon mauritianum (Jacq.) Medik., and Hypselodelphys poggeana (K.Schum.) Milne-Redh. and Spermacoce radiata (DC.) Sieber ex Hiern are also supported through in vitro and in vivo studies for managing BPH through recuperation in patients with chronic long-term illnesses, as measured by the International Prostate Symptom Score.
CONCLUSION
The review proposes and endorses careful utilization of conventional medications that may be investigated further to discover possible PDE-5, 5 alpha-reductase, an alpha-blocker inhibitor for managing BPH. Even though most conventional formulations, such as 5 alpha-reductase, are readily available, systemic assessment of the effectiveness and mechanism of action of the herbal constituents is still necessary to identify novel chemical moieties that can be further developed for maximum efficacy. However, there exist abundant botanicals and medicinal plants across several regions of Africa, Asia, and the Americas, which can be further studied and developed for utilization as a potential phytotherapeutic for the management of BPH.
Topics: Prostatic Hyperplasia; Humans; Male; Phytochemicals; Plants, Medicinal; Animals; Phytotherapy; Plant Extracts; 5-alpha Reductase Inhibitors
PubMed: 38636573
DOI: 10.1016/j.jep.2024.118207 -
International Journal of Pharmaceutical... 2024Alopecia is a chronic dermatological disorder affecting men and women worldwide. Given the high incidence and significant impact on patients' well-being, options for...
BACKGROUND
Alopecia is a chronic dermatological disorder affecting men and women worldwide. Given the high incidence and significant impact on patients' well-being, options for managing and treating alopecia are essential. Topical available options remain limited and oral products may result in adverse effects. TrichoFoam™ is a ready-to-use foaming vehicle developed for compounding pharmacies and formulated with gentle, non-irritating, and sensory-pleasant ingredients.
OBJECTIVE
The purpose of this study was to assess topical foams' physicochemical and microbiological stabilities of formulations compounded with TrichoFoam™ as the ready-touse vehicle.
METHODS
HPLC analyses were conducted in a bracketed study covering concentrations of 0.1% to 2.0% of caffeine, 0.01% to 0.1% of clobetasol propionate, 0.1% to 0.25% of dutasteride, 0.25% to 0.50% of nicotinamide, and 0.25% to 2.5% of progesterone compounded with TrichoFoam™. Antimicrobial Effectiveness Testing was conducted at the beginning and end of the studies.
RESULTS
Most formulations presented a beyond-use date of at least 90-180 days, except for clobetasol propionate, which showed compatibility for 14 days, and dutasteride 0.25%, which showed a BUD of 30 days.
CONCLUSION
This validates the stability of the active pharmaceutical ingredients from different pharmacological classes with TrichoFoam™, suggesting that this ready-to-use vehicle can be an excellent alternative for personalized alopecia treatment.
Topics: Male; Humans; Female; Clobetasol; Anti-Inflammatory Agents; Dutasteride; Progesterone; Caffeine; Administration, Topical; Hair; Alopecia
PubMed: 38604144
DOI: No ID Found -
Journal of the American Academy of... Jul 2024
Topics: Humans; 5-alpha Reductase Inhibitors; Alopecia; Retrospective Studies; Male; Propensity Score; Adult; Middle Aged; Female; Sexual Dysfunction, Physiological; Finasteride; Dutasteride
PubMed: 38552905
DOI: 10.1016/j.jaad.2024.03.019 -
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 -
Biomolecules Feb 2024Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate...
Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure ( 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively ( 0.596). IPCa was detected in 37.6 and 62.5%, respectively ( 0.089). The tumor GG distribution based on 5-ARI exposure was similar ( 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Magnetic Resonance Imaging; 5-alpha Reductase Inhibitors; Cyanoacrylates
PubMed: 38397430
DOI: 10.3390/biom14020193 -
Journal of the European Academy of... Feb 2024Frontal fibrosing alopecia (FFA) is a scarring alopecia with fronto-temporo-parietal hairline recession. Although no proven treatment for FFA exists, dutasteride has... (Review)
Review
Frontal fibrosing alopecia (FFA) is a scarring alopecia with fronto-temporo-parietal hairline recession. Although no proven treatment for FFA exists, dutasteride has been suggested as a potential treatment option. We aimed to evaluate the therapeutic response of oral dutasteride in FFA patients. The identification and selection of studies were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 criteria. To assess the risk of bias for each study, we used the Cochrane's risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool. A random effects model meta-analysis was performed. Estimated proportion of stabilization for eligible studies was calculated to evaluate the effectiveness of dutasteride for treating FFA. Among patients who achieved stabilization, subgroup analysis was conducted on those showing improvement. Seven studies including 366 patients who received oral dutasteride were identified. The estimated proportion of patients who experienced stabilization of FFA with oral dutasteride was 0.628 (95% CI: 0.398-0.859). In subgroup analyses of patients who experienced improvement, the estimated proportion of improvement was 0.356 (95% CI: 0.163-0.549). In this systematic review and meta-analysis, oral dutasteride revealed to be a good treatment option for disease stabilization or improvement in patients with FFA.
PubMed: 38357767
DOI: 10.1111/jdv.19802