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1.
Urologiia ; (5): 82-86, 2020 Nov.
Artigo em Russo | MEDLINE | ID: mdl-33185353

RESUMO

An increase in life expectancy and the number of older and elderly men, an improvement in the quality of medical care and socio-economic factors in most countries contributed to an increase in the number of patients with benign prostatic hyperplasia (BPH). Currently, improvement of the quality of life is the mainstay of strategy for managing patients with BPH, as well as prevention of complications and the need for surgery. In this regard, the pharmacotherapy with 1-adrenergic blockers (1-AB) is widely used as an effective method for improving lower urinary tract symptoms and reducing the risk of BPH progression. Given that the quality of life is becoming increasingly important in evaluating the efficiency of BPH treatment, including therapy in elderly patients, it is necessary to take into account its effect on sexual function, when choosing a particular drug. The use of 1-AB can be accompanied by side effects manifested by various sexual disorders. Alfuzosin does not adversely affect sexual function in men with BPH, may improve erectile and ejaculatory function and should be considered as the drug of choice, especially in sexually active men and patients who already suffer from worsening ejaculatory function while using another 1-AB.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Antagonistas Adrenérgicos alfa/efeitos adversos , Idoso , Humanos , Masculino , Hiperplasia Prostática/tratamento farmacológico , Qualidade de Vida
2.
Urologe A ; 59(10): 1187-1194, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32930822

RESUMO

BACKGROUND: In an aging society an increase of benign prostatic obstruction (BPO) requiring treatment is to be expected and the proportion of patients with cardiovascular comorbidities under anticoagulation is also increasing. As the operative treatment of BPO can be problematic, the hemostatic effect of the techniques is of particular importance. OBJECTIVE: This review article discusses the data situation on the bleeding risk of established surgical techniques and the statement of the European Association of Urology (EAU) guidelines "EAU guidelines on management of non-neurogenic male lower urinary tract symptoms (LUTS), incl. benign prostatic obstruction (BPO)" on this topic. MATERIAL AND METHODS: Data analysis from PubMed. RESULTS: The EAU guidelines favor transurethral laser vaporization of the prostate using "greenlight", thulium or diode laser and laser enucleation using a holmium or thulium laser in this patient collective. The bipolar is superior to monopolar transurethral resection (TUR-P) in hemostasis. In the future bipolar enucleation of the prostate (BipoLEP) can be an alternative under good hemostasis. Bleeding is a rare complication after recently established minimally invasive techniques, such as Urolift®, I­TIND© and Rezum™, the same applies to prostate artery embolization. Aqua-ablation/AquaBeam® seems to be unsuitable due to frequent hematuria. Surgical adenomectomy can be associated with a high risk of bleeding. CONCLUSION: According to current data, transurethral laser vaporization and enucleation of the prostate are the treatment of choice for patients under anticoagulation; however, other transurethral techniques, such as BipoLEP have an acceptable risk of bleeding and can be an alternative depending on local resources. Newer minimally invasive approaches could become more important in the future.


Assuntos
Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Anticoagulantes/efeitos adversos , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/cirurgia , Resultado do Tratamento
3.
Hinyokika Kiyo ; 66(9): 289-292, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-32993272

RESUMO

We retrospectively investigated the clinical course of α1 blocker discontinuation in patients who had lower urinary tract symptoms with benign prostate hypertrophy (LUTS/BPH) and received combination therapy ofdutasteride and α1 blocker. Among the patients with LUTS/BPH who had been receiving combination therapy, those who wished to reduce the number ofprescribed drugs and discontinue the use of α1 blocker because ofsymptom improvement were recruited in this study. Symptom scores including International Prostate Symptom Score (IPSS) and overactive bladder symptom score (OABSS), parameters ofuroflowmetry and prostate volume (PV) were evaluated at the time of α 1 blocker discontinuation. Twenty-two patients discontinued the use of α 1 blocker. The mean PV at the time of α 1 blocker discontinuation was 43.2 ml, and the mean duration ofcombination therapy was 39.4 months. In 11 (50%) patients, dutasteride monotherapy without α1 blocker was maintained for a mean follow-up of 10.5 months (9-12 months) after α1 blocker discontinuation (Non-resumption group). In the other 11 patients (50%), α1 blocker was resumed because ofthe patient's request to resume the use of α1 blocker (Resumption group). The mean length ofdutasteride monotherapy was 4. 5 months (1-8 months) in the resumption group. Compared with the non-resumption group, IPSS total score and storage sub-score ofIPSS at the time of α1 blocker discontinuation were significantly higher in the resumption group. Based on the ROC curve, IPSS total score <16, IPSS voiding/storage symptom score <7, OABSS <7 and PV 54 ml or more at the time of α1 blocker discontinuation were predictors ofnon-resumption of α1 blocker. These results suggest that if LUTS is controlled by a long-term combination therapy ofdutasteride and α1 blocker and still PV is large enough, α1 blocker can be discontinued.


Assuntos
Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Quimioterapia Combinada , Dutasterida/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
4.
Life Sci ; 260: 118414, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926929

RESUMO

AIM: To investigate the possible modulatory effect of febuxostat in testosterone-induced benign prostatic hyperplasia (BPH) in rats with emphasis on xanthine oxidase (XO)/Janus Kinases (JAK)/signal transducer and activator of transcription (STAT) axis. MAIN METHODS: Male Wistar rats were treated with testosterone with/out febuxostat. Effect of febuxostat on BPH was assessed at the structural level by histopathology and determination of prostate weight/index. Cyclin D1 protein expression was assessed immunohistochemically and the ratio of Bax/Bcl-2 mRNA expression was determined by real time polymerase chain reaction analysis (RT-PCR). Besides, uric acid serum level was determined colorimetrically. Prostatic XO activity, as well as oxidative stress and inflammatory markers were evaluated. Additionally, western blot analysis was performed for determination of JAK-1 and phosphorylated form of STAT-3 expression in tissues. KEY FINDINGS: Results revealed that febuxostat inhibited the increase in prostatic weight and index compared to testosterone-treated group. Additionally, febuxostat ameliorated testosterone-induced histopathological changes, prevented the rise in cyclin D1 expression and enhanced Bax/Bcl2 ratio. Febuxostat suppressed testosterone induced- increase in XO activity in prostates and serum level of uric acid. Moreover, it regulated oxidative stress markers including; malondialdehyde (MDA), superoxide dismutase (SOD) activity and glutathione (GSH) content. Also, it inhibited the increase in prostate contents of interleukin-6 (IL-6), interleukin-1ß (IL-1 ß), tumor necrosis factor (TNF-α) and nuclear factor (NF-κB). Interestingly, febuxostat markedly reduced JAK-1 and subsequent phosphorylation of STAT-3 protein expression. SIGNIFICANCE: Febuxostat ameliorates testosterone-induced BPH via suppressing XO/JAK/STAT axis. This may help to re-purpose the use of XO inhibitors.


Assuntos
Febuxostat/farmacologia , Regulação Neoplásica da Expressão Gênica/genética , Supressores da Gota/farmacologia , Janus Quinase 1/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Testosterona/toxicidade , Androgênios/toxicidade , Animais , Janus Quinase 1/genética , Masculino , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos , Ratos Wistar , Fator de Transcrição STAT3/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-32722374

RESUMO

(1) Background: Patients with benign prostatic hyperplasia (BPH) were questioned about quality of life and sleep. Most BPH patients were treated with alpha-1 adrenergic receptor antagonists, which could improve cerebral blood flow for 1-2 months. Patients with ischemic stroke (IS) could experience cerebral autoregulation impairment for six months. The relationship between BPH and recurrent IS remains unclear. The aim of this study was to determine the risk of one-year recurrent IS conferred by BPH. (2) Methods: We used data from the Taiwanese National Health Insurance Database to identify newly diagnosed IS cases entered from 1 January 2008 to 31 December 2008. Patients were followed until the recurrent IS event or 365 days after the first hospitalization. The risk factors associated with one-year recurrent IS were assessed using Cox proportional hazards regression. (3) Results: Patients with BPH had a higher risk of recurrent IS (12.11% versus 8.15%) (adjusted hazard ratio (HR): 1.352; 95% confidence interval (CI): 1.028-1.78, p = 0.031). Other risk factors included hyperlipidemia (adjusted HR: 1.338; 95% CI: 1.022-1.751, p = 0.034), coronary artery disease (adjusted HR: 1.487; 95% CI: 1.128-1.961, p = 0.005), chronic obstructive pulmonary disease (adjusted HR: 1.499; 95% CI: 1.075-2.091, p = 0.017), and chronic kidney disease (adjusted HR: 1.523; 95% CI: 1.033-2.244, p = 0.033). (4) Conclusion: Patients with BPH who had these risk factors had an increased risk of one-year recurrent IS. The modification of risk factors may prevent recurrent IS.


Assuntos
Isquemia Encefálica/epidemiologia , Hiperplasia Prostática/complicações , Qualidade de Vida/psicologia , Acidente Vascular Cerebral/epidemiologia , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/epidemiologia , Receptores Adrenérgicos alfa 1 , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/psicologia
8.
Medicine (Baltimore) ; 99(22): e20240, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481389

RESUMO

Studies suggest that the use of alpha-blockers increases the risk of dementia in patients with benign prostate hyperplasia (BPH). Due to study limitations, the relationship between the use of alpha-blockers, such as tamsulosin, and the risk of dementia is still unclear. However, alpha1-adrenoreceptors are also present in the brain, so there is potential for adverse effects on cognitive function. Therefore, we investigated possible associations between the use of alpha-blockers and aggravation of cognitive decline in dementia patients using a clinical data analytic solution called the Smart Clinical Data Warehouse (CDW).We retrospectively investigated clinical data using the Smart CDW of Hallym University Medical Center from 2009 to 2019. We enrolled patients with probable Alzheimer disease (AD) who had completed the Mini-Mental State Examination (MMSE) at least twice during follow-up, and who had BPH. We compared the difference in MMSE scores between patients who took tamsulosin for >1000 days and those who did not take any alpha-blocker. We tested the effect of tamsulosin on cognitive decline in patients with AD, using propensity score-matched logistic regression analysis.Eligible cases were included in the tamsulosin (n = 68) or no-medication (n = 153) groups. After propensity score matching, clinical characteristics such as educational attainment and vascular risk factors were similar in the tamsulosin and no-medication groups. The MMSE scores did not differ significantly between the tamsulosin and no-medication groups (P = .470).The results suggest that tamsulosin for BPH is not associated with worsening of the cognitive decline in patients with AD.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/efeitos adversos , Agentes Urológicos/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Doença de Alzheimer/complicações , Data Warehousing , Humanos , Masculino , Pontuação de Propensão , Hiperplasia Prostática/complicações , Análise de Regressão , Estudos Retrospectivos , Tansulosina/uso terapêutico , Agentes Urológicos/uso terapêutico
9.
Pol Merkur Lekarski ; 48(285): 188-194, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32564045

RESUMO

The standard pharmacotherapy of benign prostatic hyperplasia (BPH) may also alleviate potential kidney dysfunction resulting from the development of obstructive uropathy in the course of BPH. AIM: The aim of study was to evaluate the effect of treatment with α-1- adrenolytic agent (tamsulosin) and 5-α-reductase inhibitor (finasteride) on renal function in rats. MATERIALS AND METHODS: Four groups of rats were studied: 1 - controls, 2 - rats with metoclopramide-induced hyperprolactinemia BPH model, 3 - rats with BPH treated with tamsulosin, 4 - rats with BPH treated with finasteride. BPH presence was verified by histopathological examination. The renal function was assessed by histopathological examination, and the laboratory assessment of the classic nitrogen parameters and new kidney function markers (cystatin C; CysC, kidney injury molecule-1; KIM-1). RESULTS: In group 2, BPH development was confirmed by histopathological examination, without simultaneous significant kidney disturbances. Compared to the controls, BPH animals exhibited significant proteinuria, and increased concentration and daily urinary excretion of CysC and KIM- 1. Treatment with tamsulosin significantly improved the histopathological image of the prostate without affecting renal structure and led to reduced blood urea and proteinuria. Treatment with finasteride also significantly reduced the histopathological signs of BPH without changing the image of the kidneys, and reduced CysC concentration and daily CysC excretion with urine compared to group 2 individuals. CONCLUSIONS: In the course of experimental hyperprolactinemiainduced BPH, kidney tubulopathy developed, which was indicated by KIM-1 and CysC disturbances in urine. The administration of finasteride reduced renal dysfunction to a higher degree, bringing the concentration and daily excretion of CysC back to normal.


Assuntos
Inibidores de 5-alfa Redutase , Hiperprolactinemia , Hiperplasia Prostática , Inibidores de 5-alfa Redutase/uso terapêutico , Animais , Hiperprolactinemia/tratamento farmacológico , Masculino , Modelos Teóricos , Oxirredutases , Hiperplasia Prostática/tratamento farmacológico , Ratos
10.
Prostate ; 80(12): 938-949, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32542667

RESUMO

BACKGROUND: The clinical manifestation of benign prostatic hyperplasia (BPH) is causally linked to the inflammatory microenvironment and proliferation of epithelial and stromal cells in the prostate transitional zone. The CXC-chemokine interleukin-8 (IL-8) contributes to inflammation. We evaluated the expression of inflammatory cytokines in clinical specimens, primary cultures, and prostatic lineage cell lines. We investigated whether IL-8 via its receptor system (IL-8 axis) promotes BPH. METHODS: The messenger RNA and protein expression of chemokines, including components of the IL-8 axis, were measured in normal prostate (NP; n = 7) and BPH (n = 21), urine (n = 24) specimens, primary cultures, prostatic lineage epithelial cell lines (NHPrE1, BHPrE1, BPH-1), and normal prostate cells (RWPE-1). The functional role of the IL-8 axis in prostate epithelial cell growth was evaluated by CRISPR/Cas9 gene editing. The effect of a combination with two natural compounds, oleanolic acid (OA) and ursolic acid (UA), was evaluated on the expression of the IL-8 axis and epithelial cell growth. RESULTS: Among the 19 inflammatory chemokines and chemokine receptors we analyzed, levels of IL-8 and its receptors (CXCR1, CXCR2), as well as, of CXCR7, a receptor for CXCL12, were 5- to 25-fold elevated in BPH tissues when compared to NP tissues (P ≤ .001). Urinary IL-8 levels were threefold to sixfold elevated in BPH patients, but not in asymptomatic males and females with lower urinary tract symptoms (P ≤ .004). The expression of the IL-8 axis components was confined to the prostate luminal epithelial cells in both normal and BPH tissues. However, these components were elevated in BPH-1 and primary explant cultures as compared to RWPE-1, NHPrE1, and BHPrE1 cells. Knockout of CXCR7 reduced IL-8, and CXCR1 expression by 4- to 10-fold and caused greater than or equal to 50% growth inhibition in BPH-1 cells. Low-dose OA + UA combination synergistically inhibited the growth of BPH-1 and BPH primary cultures. In the combination, the drug reduction indices for UA and OA were 16.4 and 7852, respectively, demonstrating that the combination was effective in inhibiting BPH-1 growth at significantly reduced doses of UA or OA alone. CONCLUSION: The IL-8 axis is a promotor of BPH pathogenesis. Low-dose OA + UA combination inhibits BPH cell growth by inducing autophagy and reducing IL-8 axis expression in BPH-epithelial cells.


Assuntos
Interleucina-8/metabolismo , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Receptores CXCR/metabolismo , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Humanos , Interleucina-8/biossíntese , Interleucina-8/genética , Masculino , Ácido Oleanólico/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CXCR/biossíntese , Receptores CXCR/genética , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia
11.
BMC Complement Med Ther ; 20(1): 150, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32416730

RESUMO

BACKGROUND: Our previous study revealed the extract from the bark of an Amazonian tree Pao Pereira can suppress benign prostatic hyperplasia (BPH) in a rat model. Herein, we examined its inhibitory effects on human BPH cells and dissect its molecular mechanism. METHODS: We applied Pao extract to human BPH epithelial BPH-1 and prostate myofibroblast WPMY-1 cells. Cell viability, apoptosis and immunoblotting were performed, followed by gene expression profiling and gene set enrichment analysis (GSEA) to detect the differentially expressed genes and signaling pathway induced by Pao extract. Human ex vivo BPH explant organ culture was also used to examine the effects of Pao extract on human BPH tissues. RESULTS: Pao extract treatment inhibited viability and induced apoptosis in human BPH-1 and WPMY-1 cells. Gene expression profiling and the following validation indicated that the expression levels of pro-apoptotic genes (eg. PCDC4, CHOP and FBXO32) were induced by Pao extract in both two cell lines. GSEA further revealed that Pao extract treatment was negatively associated with the activation of NFκB signaling. Pao extract suppressed the transcriptional activity of NFκB and down-regulated its target genes involved in inflammation (CXCL5, CXCL6 and CXCL12) and extracellular matrix (ECM) remodeling (HAS2, TNC and MMP13) in both cultured cells and human ex vivo BPH explants. CONCLUSION: In both BPH epithelial and stromal cells, Pao extract induces apoptosis by upregulating the pro-apoptotic genes and inhibiting the inflammation-associated NFκB signaling via reducing phosphorylation of NFκB subunit RelA. Our data suggest that Pao extract may be a promising phytotherapeutic agent for BPH.


Assuntos
Apocynaceae/química , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Apoptose/genética , Linhagem Celular , Humanos , Masculino , Casca de Planta/química , Hiperplasia Prostática/genética
12.
Med Hypotheses ; 140: 109751, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32344304

RESUMO

COVID-19 pandemic is a major challenge for global and national healthcare providers. Number of new cases is continuously increasing with an emerging trend showing worse prognosis in males in comparison to females. Based on this observation, our proposed hypothesis is that 5-alpha-reductase inhibitors, that are commonly used for BPH treatment, may be one of the factors contributing to poorer prognosis in males.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Animais , Betacoronavirus , Finasterida/efeitos adversos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Masculino , Pandemias , Prognóstico , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/embriologia , Fatores Sexuais
13.
Nat Commun ; 11(1): 1987, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332823

RESUMO

Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy.


Assuntos
Próstata/patologia , Hiperplasia Prostática/genética , Serina-Treonina Quinases TOR/antagonistas & inibidores , Agentes Urológicos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Biomarcadores/análise , Metilação de DNA , Epigênese Genética , Epigenômica , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/genética , Medicina de Precisão/métodos , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/efeitos dos fármacos , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , RNA-Seq , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Agentes Urológicos/farmacologia , Sequenciamento Completo do Genoma
14.
J Urol ; 204(4): 793-798, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32294395

RESUMO

PURPOSE: Depressed mood and suicidality reported with 5α-reductase inhibitors (finasteride and dutasteride) during post-marketing surveillance resulted in the addition of depression risk to finasteride labeling. As peer reviewed studies are limited and have reported mixed findings, we further evaluated 5α-reductase inhibitor exposure and depression risk using sequence symmetry analysis. MATERIALS AND METHODS: National Veterans Health Administration administrative data were used to identify 53,848 male patients initiating 5α-reductase inhibitor therapy during fiscal year 2014. Incident depression events were assessed separately using the 2 measures of antidepressant prescription and depression diagnosis. Symmetry ratios were calculated as the ratio of patients with an incident depression event in the year following 5α-reductase inhibitor initiation to the year preceding initiation. An identical exposure counterfactual analysis was conducted among veterans initiating α1-adrenergic receptor antagonists. RESULTS: Incident antidepressant prescribing was observed in 2,563 patients following 5α-reductase inhibitor initiation and 3,051 patients preceding 5α-reductase inhibitor initiation (SR 0.84, 95% CI 0.80-0.89). Similar findings were observed for incident depression diagnosis (SR 0.83, 95% CI 0.79-0.86). Stratification by age group, 5α-reductase inhibitor agent, antidepressant class, prior α1-adrenergic receptor antagonist exposure and depression diagnosis type failed to demonstrate any positive association between 5α-reductase inhibitor and depression. Nearly identical results were observed in the α1-adrenergic receptor antagonist analysis (SR 0.87, 95% CI 0.84-0.90). CONCLUSIONS: Initiation of a 5α-reductase inhibitor was not associated with increased risk of depression. Our findings support the hypothesis that depression is more likely attributable to underlying benign prostatic hyperplasia and associated lower urinary tract symptoms than 5α-reductase inhibitor exposure.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Depressão/induzido quimicamente , Depressão/epidemiologia , Dutasterida/efeitos adversos , Finasterida/efeitos adversos , Hiperplasia Prostática/tratamento farmacológico , Inibidores de 5-alfa Redutase/uso terapêutico , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Top Companion Anim Med ; 38: 100405, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115076

RESUMO

The monitoring of serum prostatic biomarkers during the treatment will help clinicians to know the statement of the response to finasteride in dogs affected by benign prostatic hyperplasia (BPH). The present study was aimed to assess changes in the serum canine prostate-specific esterase (CPSE), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), testosterone, dihydrotestosterone (DHT) and prostate volume evaluation using ultrasonographic examination during the treatment with finasteride in BPH-induced dogs. Twenty dogs were divided into 4 groups (n = 5): BPH + finasteride group, dogs which were induced for BPH and received oral finasteride once daily for 1 month; BPH group, dogs which were induced for BPH and received placebo; finasteride group, normal dogs which received finasteride; and normal group, normal intact dogs which did not receive treatment. Blood sampling and ultrasonography examination were performed on days 0, 14, and 28. The administration of finasteride led to a significant decrease in the concentration of the prostate-specific biomarkers (PSA, CPSE), DHT, testosterone, and the volume of the prostate in BPH + finasteride group compared with the BPH group during 1 month. Interestingly, the PAP concentration did not change in the BPH-induced dogs and in dogs treated with finasteride. It seems that the monitoring of serum PSA and CPSE levels and ultrasonographic examination of the prostate are useful methods for following up the response to finasteride treatment in dogs affected by BPH.


Assuntos
Biomarcadores/sangue , Doenças do Cão/tratamento farmacológico , Finasterida/farmacologia , Hiperplasia Prostática/veterinária , Inibidores de 5-alfa Redutase , Fosfatase Ácida/sangue , Animais , Di-Hidrotestosterona/sangue , Doenças do Cão/sangue , Doenças do Cão/enzimologia , Cães , Esterases/sangue , Estradiol/administração & dosagem , Masculino , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Testosterona/administração & dosagem , Testosterona/sangue , Ultrassonografia/veterinária
16.
J Urol ; 204(2): 325-331, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32167867

RESUMO

PURPOSE: Although clinical trials demonstrate 5-alpha reductase inhibitors are efficacious treatments for benign prostatic hyperplasia, they have low reported medication adherence outside of clinical trials. We evaluated real-world drug adherence and clinical outcomes in Medicare patients with lower urinary tract symptoms from benign prostatic hyperplasia managed with 5-alpha reductase inhibitor therapy. MATERIALS AND METHODS: Using health care and pharmacy claims from Partners Healthcare Medicare Accountable Care Organization enrollees (January 2009 to July 2018), we identified men initiating a 5-alpha reductase inhibitor for benign prostatic hyperplasia with more than 1 medication dispensation. Adherence was calculated as an 80% or greater proportion of days covered. A Cox proportional hazards model was used to evaluate the primary outcome of treatment failure, defined as any benign prostatic hyperplasia related surgery. RESULTS: Among 3,107 men initiating 5-alpha reductase inhibitor therapy for benign prostatic hyperplasia and filling at least 2 prescriptions, 74.9% had high medication adherence during the first year. Patients with low adherence had 29% higher hazards of undergoing surgical intervention (95% CI 1.02-1.59, p=0.036) after adjusting for age, benign prostatic hyperplasia severity, presence of hematuria, bladder stones and type of 5-alpha reductase inhibitors. The presence of bladder stones (HR 1.70, 95% CI 1.02-2.86, p=0.04) and finasteride vs dutasteride use (HR 1.41, 95% CI 1.01-1.98, p=0.05) were also risk factors for surgical intervention. CONCLUSIONS: Among Medicare patients 5-alpha reductase inhibitor treatment adherence was high and associated with lower hazards of surgical intervention. 5-Alpha reductase inhibitor therapy may be more feasible for older men with benign prostatic hyperplasia than previously reported and demonstrates modest clinical benefit.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Dutasterida/uso terapêutico , Finasterida/uso terapêutico , Adesão à Medicação , Hiperplasia Prostática/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Medicare , Estados Unidos
17.
Medicine (Baltimore) ; 99(3): e18712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011446

RESUMO

BACKGROUND: Drug therapy for lower urinary tract symptoms (LUTS) secondary to benign prostate hyperplasia (BPH) is a major and popular method. However, the therapeutic strategy is still not clear enough up to now. The purpose of this study was to compare the relative safety and efficacy of different types of phosphodiesterase type 5 inhibitors (PDE5-Is) with tamsulosin for the treatment of LUTS secondary to BPH. METHODS: Databases including PubMed, OpenGrey, Embase, Cochrane Library, and Web of Science will be searched to identify qualified studies. We will use the Stata version 13.0 to conduct the network meta-analysis (NMA) with a random or fixed effects model of Bayesian framework. International prostate symptom score (IPSS), maximum urinary flow fate (Qmax) and their credible intervals (CI) will be used to compare every medical intervention with the efficacy and safety, including sildenafil plus tamsulosin, tadalafil plus tamsulosin, vardenafil plus tamsulosin. And the ranking of probability of different interventions will be estimated by comparing the surface under the cumulative ranking curve (SUCRA). RESULTS: A high quality-synthesis of the current evidence for comparing with different doses or types of PDE5-Is combined with tamsulosin to the treatment of LUTS secondary to BPH will be provided. CONCLUSIONS: This NMA and systematic review will generate evidence to help choose the best combination for treatment of LUTS secondary to BPH.PROSPERO registration number: PROSPERO CRD 42019139062.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Teorema de Bayes , Quimioterapia Combinada , Humanos , Masculino , Metanálise em Rede , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Citrato de Sildenafila/uso terapêutico , Tadalafila/uso terapêutico , Tansulosina/administração & dosagem , Tansulosina/efeitos adversos , Dicloridrato de Vardenafila/uso terapêutico
18.
Actas urol. esp ; 44(1): 9-13, ene.-feb. 2020.
Artigo em Espanhol | IBECS | ID: ibc-192785

RESUMO

CONTEXTO: El Pygeum africanum (P. africanum) sigue siendo utilizado por parte de los urólogos para el tratamiento de los síntomas urinarios del tracto urinario inferior secundarios a hiperplasia benigna de próstata. Adquisición de la evidencia: Se ha realizado una revisión no exhaustiva sobre el P. africanum, sus mecanismos de acción, tanto «in vitro» como «in vivo», de los ensayos clínicos y en la práctica clínica habitual. Síntesis de la evidencia: Se muestran las conclusiones de la revisión y las reflexiones de los autores sobre la utilización del P. africanum. CONCLUSIONES: Aunque con un nivel de evidencia 4 (basado en la opinión de expertos), la utilización del P. africanum parece ser una opción en el arsenal terapéutico del urólogo


CONTEXT: Pygeum africanum(P. africanum) is still being employed in urology practice for the treatment of lower urinary tract symptoms secondary to benign prostate hyperplasia. Evidence acquisition: A non-exhaustive review has been carried out about P. africanum, its mechanisms of action "in vitro" as well as "in vivo", clinical trials and routine clinical practice. Evidence synthesis: The conclusions of the review and the reflections of the authors on the use of P. africanum are described. CONCLUSIONS: Although with an evidence level IV (based on expert opinion) the use of P. africanum seems to be an option in the urological therapeutic arsenal


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Medicina Baseada em Evidências , Hiperplasia Prostática/tratamento farmacológico , Prunus africana/química , Extratos Vegetais/uso terapêutico , Ensaios Clínicos como Assunto
19.
Fertil Steril ; 113(1): 21-50, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32033719

RESUMO

Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Finasterida/efeitos adversos , Disfunções Sexuais Fisiológicas/induzido quimicamente , Disfunções Sexuais Fisiológicas/diagnóstico , Suspensão de Tratamento/tendências , Alopecia/tratamento farmacológico , Alopecia/fisiopatologia , Ensaios Clínicos como Assunto/métodos , Humanos , Masculino , Estudos Observacionais como Assunto/métodos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/fisiopatologia , Disfunções Sexuais Fisiológicas/fisiopatologia , Síndrome
20.
Int J Mol Sci ; 21(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093293

RESUMO

We investigated the metabolite changes of Morus roots (MRs) according to different cultivar families (Simheung, Daesim, Cheong-il, Sangchon, Daeseong, Suhong, Suwon, and Igsu) using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to understand the relationship between different cultivars and metabolite changes. Data were analyzed by partial least squares discriminant analysis (PLS-DA), and samples were successfully separated in PLS-DA scores. Eight metabolites in the electrospray ionization (ESI)-positive mode and 16 metabolites in the ESI-negative mode contributed to the separation in PLS-DA. Our data suggest that comparative analysis of MR metabolites according to different cultivars is useful to better understand the relationship between the different cultivars and metabolite changes. Furthermore, we analyzed the MRs for their ability to improve benign prostatic hyperplasia (BPH). LNCaP cells were used to evaluate the prostate-specific antigen (PSA) inhibitory activity of MRs, and, amongst them, the extract with the highest activity was selected. Igsu demonstrated the highest inhibition effect of prostate-specific antigen (PSA) expression among the MR cultivars. Igsu was also evaluated by administration in a testosterone-induced benign prostatic hyperplasia model in Sprague-Dawley rats. Igsu was shown to ameliorate BPH as evidenced by the prostate index, expression of androgen receptor (AR) signaling-related protein, growth factors, cell proliferation-related proteins, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling proteins, and histological analysis. Hence, this study strongly suggests that Igsu may have a beneficial effect of on BPH.


Assuntos
Morus/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Próstata/metabolismo , Hiperplasia Prostática , Testosterona/efeitos adversos , Animais , Masculino , Extratos Vegetais/química , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Testosterona/farmacologia
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