RESUMEN

Andrographis paniculata (Burm.f.) Nees has been used traditionally in treating many diseases. This study investigated its potential to attenuate benign prostatic hyperplasia (BPH) in male rats. Rats were castrated, divided into five groups and orally treated for 14 days with: normal saline,10 mg/kg testosterone propionate sc, finasteride (0.5 mg/kg), 500 mg, and 1500 mg/kg of Andrographis paniculata. Relative prostate weights, the correlation between prostatic index and volume and the prostates' histopathology as well as Prostate Specific Antigen (PSA) were evaluated. Following treatment with Andrographis paniculata, the prostate weights were significantly reduced (p < 0.05) and the lost correlation observed in the untreated group was restored. Histopathological assessment showed reduced epithelial hyperplasia following treatment with a resultant thin layer of epithelial cells, similar to the healthy normal control group. The level of PSA was also reduced. Andrographis paniculata, thus, has the potential to inhibit the proliferation observed in testosterone-induced BPH.

RESUMEN

LDOM has enhanced treatment options for female AGA, yet its combined efficacy with therapies such as spironolactone, finasteride, or dutasteride remains inadequately explored. This study aims to compare the efficacy and safety of LDOM in combination with spironolactone versus LDOM with finasteride or dutasteride in women with AGA. Our analysis revealed that both combination therapies produced similar improvements in hair growth and had comparable safety profiles. Although the LDOM with finasteride/dutasteride group showed a greater average increase in hair width and density, these differences were not statistically significant. These results endorse the use of LDOM in combination with either spironolactone or finasteride/dutasteride for female AGA, and underscore the necessity for further research to validate these findings and assess long-term treatment outcomes.

Asunto(s)

Alopecia , Quimioterapia Combinada , Dutasterida , Finasterida , Minoxidil , Espironolactona , Humanos , Femenino , Finasterida/administración & dosificación , Dutasterida/administración & dosificación , Espironolactona/administración & dosificación , Alopecia/tratamiento farmacológico , Minoxidil/administración & dosificación , Adulto , Resultado del Tratamiento , Quimioterapia Combinada/métodos , Persona de Mediana Edad , Inhibidores de 5-alfa-Reductasa/administración & dosificación , Administración Oral , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Adulto Joven , Estudios Retrospectivos

RESUMEN

Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Unsupervised clustering revealed molecular subgroups characterized by expression changes in a large set of genes associated with resistance to finasteride, a 5α-reductase inhibitor. Pathway analyses within this gene cluster found finasteride administration induced changes in fatty acid metabolism, amino acid metabolism, immune response, steroid hormone metabolism, and kinase activity within the transitional zone. We found that patients without this transcriptional response were highly likely to develop clinical progression, which is expected in 13.2% of finasteride-treated patients. Importantly, a patient's transcriptional response to finasteride was associated with their pre-treatment kinase expression. Further, we identified novel expression signatures of finasteride resistance among the transcriptionally responded patients. These patients showed different gene expression profiles at baseline and increased prostate transitional zone volume compared to the patients who responded to the treatment. Our work suggests molecular mechanisms of clinical resistance to finasteride treatment that could be potentially helpful for personalized BPH treatment as well as new drug development to increase patient drug response.

Asunto(s)

Doxazosina , Finasterida , Próstata , Enfermedades de la Próstata , Próstata/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Finasterida/farmacología , Finasterida/uso terapéutico , Doxazosina/farmacología , Doxazosina/uso terapéutico , Agentes Urológicos/farmacología , Agentes Urológicos/uso terapéutico , Resistencia a Medicamentos , Enfermedades de la Próstata/tratamiento farmacológico , Humanos

RESUMEN

BACKGROUND: There is a long-standing debate if finasteride, a medication used to treat benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA), can cause psychiatric side effects. OBJECTIVE: The goal of this large-scale population-based study was to determine whether finasteride therapy for BPH and AGA is associated with the emergence of mental health conditions. METHODS: This observational case-control study compared the data from patients with BPH who received finasteride 5 mg daily and patients with AGA who received finasteride 1 mg daily with age- and gender-matched controls. The incidence of psychological health outcomes such as depression, anxiety, neuroses, bipolar disorder, schizophrenia, psychoses and alcohol abuse within 2 years of the initiation of finasteride therapy has been evaluated and compared between the finasteride groups and controls. RESULTS: The BPH group included 307 men with a mean age of 61.5 (±17.4) years and 1218 controls. Mental health outcomes recorded in 2.3% of the patients, with no significant increase in rate when compared to controls. The AGA group consisted of 23,227 men with a mean age of 31.4 (±10.3) years and 39,444 controls. Only One percent of AGA patients developed psychiatric disorders. In comparison to controls, patients with AGA had higher rates of anxiety and depression (0.6% vs. 0.4%, p = 0.04, and 0.5% vs. 0.4%, p = 0.007, respectively). In multivariate regression models, finasteride was found as one of the risk factors for anxiety (OR 1.449, p = 0.002) and depression (OR 1.439, p = 0.003) when stratified to age, sector, socioeconomic status and comorbidities. CONCLUSIONS: According to our research, finasteride users had a very low rate of adverse mental health effects, with no increase in psychological sequelae in BPH patients and a slight increase in anxiety and depression in AGA patients.

RESUMEN

Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, -7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects.

Asunto(s)

Inhibidores de 5-alfa-Reductasa , Alopecia , Vesículas Extracelulares , Finasterida , Oro , Folículo Piloso , Nanopartículas del Metal , Células Madre , Finasterida/administración & dosificación , Oro/química , Oro/administración & dosificación , Alopecia/terapia , Animales , Nanopartículas del Metal/administración & dosificación , Células Madre/citología , Inhibidores de 5-alfa-Reductasa/administración & dosificación , Humanos , Liposomas , Masculino , Ratones , Ratones Endogámicos C57BL , Cabello/crecimiento & desarrollo

RESUMEN

BACKGROUND: Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase-2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH-associated LUTS. METHODS: To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed. RESULTS: NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration. CONCLUSIONS: These findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.

Asunto(s)

Celecoxib , Finasterida , Hiperplasia Prostática , Masculino , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Finasterida/farmacología , Finasterida/uso terapéutico , Humanos , Animales , Celecoxib/farmacología , Celecoxib/uso terapéutico , Ratones , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Anciano , Próstata/efectos de los fármacos , Próstata/patología , Próstata/metabolismo , Inhibidores de 5-alfa-Reductasa/farmacología , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Transporte de Electrón/efectos de los fármacos , Persona de Mediana Edad , Proteínas Mitocondriales/metabolismo , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/metabolismo , Síntomas del Sistema Urinario Inferior/patología , Complejo I de Transporte de Electrón/metabolismo

RESUMEN

Endometriosis denotes the abnormal growth of tissue resembling endometrium in ectopic sites and has largely been studied in women of reproductive age. It is an extremely rare phenomenon in men. We came across an exceptional clinical scenario of histologically proven bladder endometriosis in a 66-year-old man in relook bladder biopsy following completion of adjuvant intravesical Bacillus Calmette-Guerin induction course for G3pTa bladder cancer. We have pencilled down pathophysiology and commonly seen predisposing factors for "endometriosis in male patients" from available case reports and applied those findings to hypothesise the disease profile of our patient in this case report.

RESUMEN

Several studies have reported side effects of finasteride (FIN), such as anxiety/depression in young men. Obesity is also positively associated with anxiety/depression symptoms; however, the impacts of long-term FIN treatment and FIN withdrawal in young obese individuals are still elusive. The present study aimed to investigate the effect of long-term treatment and its withdrawal on anxiety/depression and brain pathologies in lean and obese adult male rats. Forty-eight male Wistar rats were equally divided into two groups and fed either a normal or high-fat diet. At age 13 weeks, rats in each dietary group were divided into three subgroups: 1) the control group receiving drinking water, 2) the long-term treatment group receiving FIN orally at 5 mg/kg/day for 6 weeks, and 3) the withdrawal group receiving FIN orally at 5 mg/kg/day for 2 weeks followed by a 4-week withdrawal period. Anxiety/depression-like behaviors, biochemical analysis, brain inflammation, oxidative stress, neuroactive steroids, brain metabolites, and microglial complexity were tested. The result showed that lean rats treated with long-term FIN and its withdrawal exhibited metabolic disturbances, depressive-like behavior, and both groups showed increased neurotoxic metabolites and reduced microglial complexity. Obesity itself led to metabolic disturbances and brain pathologies, including increased inflammation, oxidative stress, and quinolinic acid, as well as reduced microglial complexity, resulting in increased anxiety- and depression-like behaviors. Interestingly, the long-term FIN treatment group in obese rats showed attenuation of depressive-like behaviors, brain inflammation, and oxidative stress, along with increased brain antioxidants, suggesting the possible benefits of FIN in obese conditions.

Asunto(s)

Inhibidores de 5-alfa-Reductasa , Ansiedad , Depresión , Dieta Alta en Grasa , Finasterida , Obesidad , Ratas Wistar , Animales , Masculino , Obesidad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Depresión/etiología , Inhibidores de 5-alfa-Reductasa/farmacología , Ratas , Finasterida/farmacología , Dieta Alta en Grasa/efectos adversos , Ansiedad/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Modelos Animales de Enfermedad

RESUMEN

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

Asunto(s)

Alopecia , Terapia por Luz de Baja Intensidad , Minoxidil , Plasma Rico en Plaquetas , Humanos , Alopecia/tratamiento farmacológico , Alopecia/terapia , Terapia por Luz de Baja Intensidad/métodos , Minoxidil/uso terapéutico , Finasterida/uso terapéutico , Dutasterida/uso terapéutico

RESUMEN

Finasteride, a steroid 5-alpha reductase inhibitor, is commonly used for the treatment of benign prostatic hyperplasia and hair loss. However, despite continued use, its environmental implications have not been thoroughly investigated. Thus, we investigated the acute and chronic adverse impacts of finasteride on Daphnia magna, a crucial planktonic crustacean in freshwater ecosystems selected as bioindicator organism for understanding the ecotoxicological effects. Chronic exposure (for 23 days) to finasteride negatively affected development and reproduction, leading to reduced fecundity, delayed first brood, reduced growth, and reduced neonate size. Additionally, acute exposure (< 24 h) caused decreased expression levels of genes crucial for reproduction and development, especially EcR-A/B (ecdysone receptors), Jhe (juvenile hormone esterase), and Vtg2 (vitellogenin), with oxidative stress-related genes. Untargeted lipidomics/metabolomic analyses revealed lipidomic alteration, including 19 upregulated and 4 downregulated enriched lipid ontology categories, and confirmed downregulation of metabolites. Pathway analysis implicated significant effects on metabolic pathways, including the pentose phosphate pathway, histidine metabolism, beta-alanine metabolism, as well as alanine, aspartate, and glutamate metabolism. This comprehensive study unravels the intricate molecular and metabolic responses of D. magna to finasteride exposure, underscoring the multifaceted impacts of this anti-androgenic compound on a keystone species of freshwater ecosystems. The findings emphasize the importance of understanding the environmental repercussions of widely used pharmaceuticals to protect biodiversity in aquatic ecosystems.

Asunto(s)

Inhibidores de 5-alfa-Reductasa , Daphnia , Finasterida , Metabolismo de los Lípidos , Contaminantes Químicos del Agua , Animales , Finasterida/toxicidad , Daphnia/efectos de los fármacos , Inhibidores de 5-alfa-Reductasa/toxicidad , Contaminantes Químicos del Agua/toxicidad , Metabolismo de los Lípidos/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Reproducción/efectos de los fármacos , Lipidómica , Daphnia magna

RESUMEN

BACKGROUND: Oral finasteride and topical minoxidil formulations are the only FDA-approved drug therapies for androgenetic alopecia (AGA). Research into dutasteride, topical finasteride, and nontopical minoxidil (low-dose oral and sublingual) formulations in the treatment of AGA has spiked within recent years. Early findings show that these alternative drug therapies may have similar to improved efficacy and safety profiles relative to the conventional treatment options. AIMS: Conducting a bibliometric analysis, compare trends in publications on these alternative drug therapies, identify key contributors, evaluate major findings from top-cited articles, and elucidate gaps in evidence. METHODS: A search was conducted on the Web of Science database for publications on the use of alternative drug therapies in the treatment of AGA. A total of 95 publications, published between January 2003-March 2024, and their citation metadata were included in the analysis. RESULTS: Dutasteride showed the greatest (n = 37) and longest (20+ years) history of publications, as well as the highest cumulative citations (n = 914); however, nontopical minoxidil showed a burst in research activity within the last 5 years (n = 33 publications since 2019). A relatively low number of randomized control trials (n = 3) for nontopical minoxidil suggests a need for higher-quality evidence. CONCLUSIONS: Our analysis reveals major trends, contributors, and gaps in evidence for alternative drug therapies for AGA, which can help inform researchers on their future projects in this growing field of study. There is enthusiasm for exploring off-label formulations: nontopical forms of minoxidil (oral and sublingual), topical finasteride, and mesotherapy.

RESUMEN

The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol.

RESUMEN

INTRODUCTION: Hair loss is driven by multiple factors, including genetics. Androgenetic alopecia (AGA) is a condition in which treatments necessitate prolonged compliance with prescribed medications. We have developed IVL3001, a long-acting injectable (LAI) formulation of finasteride encapsulated within poly lactic-co-glycolic acid microspheres, to enhance the efficacy of the finasteride and to achieve consistent positive outcomes in adults. An open-label, sequential, single-dose phase I clinical trial was designed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) of IVL3001. METHODS: A total of 40 non-smoking, healthy adult males were divided into three cohorts where the IVL3001 group received a single subcutaneous injection of 12-36 mg IVL3001 and 1 mg finasteride (Propecia®) once daily for 28 days. The plasma concentrations of finasteride, dihydrotestosterone (DHT), and testosterone were measured using liquid chromatography-tandem mass spectrometry. The tolerability of the injections was assessed, and compartment models were developed to predict the effective dose and assess PK/PD profiles. RESULTS: IVL3001 and finasteride 1 mg tablets were well tolerated. IVL3001 showed consistent plasma concentrations without bursts or fluctuations. Consistent with its mechanism of action, IVL3001 reduced DHT levels. Simulation data showed that the administration of 12-36 mg of IVL3001 every 4 weeks achieved plasma concentrations similar to finasteride, with comparable DHT reduction. CONCLUSION: The present study represents the first clinical trial to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD), and tolerability of finasteride long-acting injectables (LAI) in adults. The rapid onset of action sustained effective drug concentration and the prolonged half-life of IVL3001 suggest that it offers multiple benefits over conventional oral formulations in terms of therapeutic response and compliance. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04945226.

Asunto(s)

Inhibidores de 5-alfa-Reductasa , Alopecia , Finasterida , Humanos , Finasterida/farmacocinética , Finasterida/administración & dosificación , Finasterida/efectos adversos , Alopecia/tratamiento farmacológico , Masculino , Adulto , Inhibidores de 5-alfa-Reductasa/farmacocinética , Inhibidores de 5-alfa-Reductasa/administración & dosificación , Inhibidores de 5-alfa-Reductasa/efectos adversos , Inhibidores de 5-alfa-Reductasa/farmacología , Dihidrotestosterona/farmacocinética , Dihidrotestosterona/administración & dosificación , Dihidrotestosterona/sangre , Persona de Mediana Edad , Preparaciones de Acción Retardada , Testosterona/farmacocinética , Testosterona/sangre , Inyecciones Subcutáneas , Adulto Joven , Microesferas

RESUMEN

Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid levels and affecting androgen regulation and metabolic function. As a result, the administration of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia, hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these adverse metabolic events both in human subjects and animal models, the exact mechanisms of these actions have not been well described yet in the literature. Further well-designed clinical trials are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic syndrome. The aim of this study was to systematically review the literature concerning the role of dutasteride or finasteride in the progression of metabolic adverse events and further investigate possible pathophysiologic mechanisms.

RESUMEN

BACKGROUND: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking. AIMS: To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride). METHODS: Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment. RESULTS: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events. CONCLUSION: Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil.

Asunto(s)

Alopecia , Finasterida , Minoxidil , Medición de Resultados Informados por el Paciente , Humanos , Finasterida/administración & dosificación , Finasterida/efectos adversos , Masculino , Estudios Retrospectivos , Alopecia/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Estudios Transversales , Minoxidil/administración & dosificación , Minoxidil/efectos adversos , Administración Oral , Telemedicina , Resultado del Tratamiento , Inhibidores de 5-alfa-Reductasa/administración & dosificación , Inhibidores de 5-alfa-Reductasa/efectos adversos , Administración Cutánea , Autoimagen , Cabello/efectos de los fármacos , Quimioterapia Combinada/métodos

RESUMEN

PURPOSE: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases. MATERIALS AND METHODS: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching. RESULTS: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44-1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67-1.14; p=0.310). CONCLUSIONS: Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH.

RESUMEN

Symptomatic cerebral infarcts with cryptogenic ischemic stroke pose diagnostic challenges due to unknown etiology. Notably, up to half of young individuals with cryptogenic stroke exhibit patent foramen ovale (PFO), while finasteride, which is used for male pattern baldness, elevates testosterone levels, potentially increasing the risk of thrombosis. Here, we present a case of thalamic infarction in a 21-year-old male devoid of cerebrovascular risk factors but with PFO and finasteride use. The patient presented with short-term memory issues, otherwise lacking medical history or substance use. Examination revealed neurological deficits, with imaging indicating a left thalamic infarct. Subsequent investigations identified PFO, prompting referral for closure, yielding symptomatic improvement. Furthermore, discontinuation of finasteride was advised due to its thrombotic association. Finasteride's inhibition of 5-alpha reductase 2 increases testosterone conversion to estrogen, potentially promoting thrombosis. Finasteride use can cause thrombotic events, emphasizing its risk. In conclusion, young embolic stroke patients warrant PFO evaluation alongside hypercoagulable workup, with closure benefiting those under the age of 55. Additionally, discontinuing finasteride may mitigate thrombosis risk.

RESUMEN

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.

RESUMEN

The inhibitory effect against 5-α reductase of the ethyl acetate (EA) extract from Physalis angulata was evaluated in vitro using mouse prostate homogenates, and the suppression of benign prostatic hyperplasia (BPH) was assessed in a mouse model of testosterone-induced BPH. The EA extract exhibited a potentially inhibitory effect on 5-α reductase with an IC50 of 197 µg/ml. In BPH mice, the EA extract at a dose of 12 mg/kg was comparable to finasteride 5 mg/kg in suppressing BPH in terms of reducing absolute enlarged prostate weight (p < 0.05 vs. BPH group) and mitigating the hypertrophy of glandular elements and prostate connective tissue. Identification of chemical ingredients in the EA extract by UPLC-QTOF-MS revealed 37 substances belonging chiefly to flavonoids and physalins. Further quantification of the EA extract by HPLC-PDA methods revealed that chlorogenic acid, and rutin were the main components. Molecular docking studies of chlorogenic acid and rutin on 5-α reductase showed their high affinity to the enzyme with binding energies of -9.3 and - 9.2 kcal/mol, respectively compared with finasteride (- 10.3 kcal/mol). Additionally, chlorogenic acid inhibited 5-α reductase with an IC50 of 12.07 µM while rutin did not. The presence of chlorogenic acid in the EA extract may explain the inhibitory effects of the EA extract on 5-α reductase, and thus the suppression of BPH.

Asunto(s)

Inhibidores de 5-alfa-Reductasa , Simulación del Acoplamiento Molecular , Physalis , Extractos Vegetales , Hiperplasia Prostática , Animales , Hiperplasia Prostática/tratamiento farmacológico , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratones , Physalis/química , Inhibidores de 5-alfa-Reductasa/farmacología , Inhibidores de 5-alfa-Reductasa/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Estructura Molecular , Ácido Clorogénico/farmacología , Ácido Clorogénico/aislamiento & purificación , Próstata/efectos de los fármacos , Modelos Animales de Enfermedad

RESUMEN

We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did not resolve after 6 months of treatment with raloxifene, a selective estrogen receptor modulator. One year later, bilateral mammoplasty was performed to remove the remaining breast tissue. Finasteride, a 5-alpha-reductase inhibitor, is widely used for the treatment of androgenetic alopecia. Gynecomastia is an expected side effect of this therapy given its mechanism of action. However, only 8 cases of gynecomastia have been reported with low-dose (1 mg daily) finasteride treatment since its approval for androgenetic alopecia in 1997. This raises the concern that gynecomastia resulting from low-dose finasteride is significantly underreported, causing inadequately informed patients. Further, because of the risk of gynecomastia, it is important for prescribing physicians to counsel patients regarding this complication and to consider early intervention when finasteride-induced gynecomastia first arises to prevent fibrosis and thus irreversible gynecomastia.