5-alpha reductase inhibitor

5 - α 还原酶抑制剂
  • 文章类型: Journal Article
    目的:验证巴塞罗那磁共振成像预测模型(BCN-MRIPM)对加泰罗尼亚有临床意义的前列腺癌(csPCa),有790万居民的西班牙地区。此外,BCN-MRIPM在接受5-α还原酶抑制剂(5-ARI)的男性中得到验证.
    方法:2,212名前列腺特异性抗原血清水平>3.0ng/ml和/或可疑直肠指检者,在2022年接受了多参数MRI和靶向和/或系统活检,在加泰罗尼亚csPCa早期检测计划的十个参与者中心,被选中。120个人(5.7%)被确定为接受5-ARI治疗超过一年。使用巴塞罗那风险计算器2(BCN-RC2)回顾性评估csPCa的风险。接受5-ARI治疗少于一年的男性被排除在外。当等级组≥2时定义CsPCa。
    结果:在接受5-ARI治疗的男性中,BCN-MRIPM曲线下面积为0.824(95%CI0.783-0.842)和0.849(0.806-0.916)。第0.475页。在5-ARI天真男性中,100、97.5和95%敏感性阈值的特异性分别为2.7、29.3和39%,而43.5、46.4和47.8%,分别在5-ARI用户中。BCN-MRIPM的应用将导致减少23.8%的前列腺活检缺失5%的csPCa在5-ARI天真的男性,在5-ARI使用者中减少25%的前列腺活检而不丢失csPCa。
    结论:BCN-MRIPM已在加泰罗尼亚成功验证,特别是,第一次,在接受5-ARI治疗的男性中。
    OBJECTIVE: To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI).
    METHODS: A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2.
    RESULTS: The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783-0.842) and 0.849 (0.806-0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users.
    CONCLUSIONS: The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.
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  • 文章类型: Systematic Review
    背景:主动监测(AS)是低风险和选定中危前列腺癌(PCa)患者的标准护理。然而,缺乏关于AS期间如何影响疾病轨迹的总结证据。
    目的:评估在AS期间哪些干预措施能有效预防PCa进展。
    方法:我们查询PubMed,Scopus,和WebofScience数据库来确定研究旨在减缓AS期间疾病进展的干预措施的影响。主要终点是PCa进展,其定义必须包括病态升级。次要终点包括治疗毒性。
    结果:我们确定了22项研究,6项随机对照试验和16项观察性研究,分析了不同干预措施与AS期间PCa进展之间的关系。研究中考虑的干预措施包括5-α还原酶抑制剂(5-ARIs),他汀类药物,饮食,锻炼,氯丁酮,非索波肽三氟(FT),恩扎鲁他胺,咖啡,维生素D3和PROSTVAC。我们发现给予5-ARIs与无进展生存期改善相关(PFS;风险比:0.59;95%置信区间0.48-0.72),没有增加的毒性信号。治疗如维生素D3,氯丁酮,FT,恩杂鲁胺也显示出一定的疗效。然而,在高达88%的患者中,这些抗癌药物与治疗相关的不良事件相关.
    结论:在PCaAS患者中使用5-ARIs与较长的PFS相关。然而,对于其他干预措施,很难根据现有的薄弱证据得出明确的结论。
    结果:接受5-α还原酶抑制剂治疗的主动监测(AS)前列腺癌患者的疾病进展风险较低,最小的不良事件。其他干预措施需要更多的研究来确定其在男性AS患者中的疗效和安全性。
    BACKGROUND: Active surveillance (AS) is a standard of care for patients with low-risk and selected intermediate-risk prostate cancer (PCa). Nevertheless, there is a lack of summary evidence on how to impact disease trajectory during AS.
    OBJECTIVE: To assess which interventions prevent PCa progression effectively during AS.
    METHODS: We queried PubMed, Scopus, and Web of Science databases to identify studies examining the impact of interventions aimed at slowing disease progression during AS. The primary endpoint was PCa progression, the definition of which must have included pathological upgrading. The secondary endpoint included treatment toxicities.
    RESULTS: We identified 22 studies, six randomized controlled trials and 16 observational studies, which analyzed the association between different interventions and PCa progression during AS. The interventions considered in the studies included 5-alpha reductase inhibitors (5-ARIs), statins, diet, exercise, chlormadinone, fexapotide triflutate (FT), enzalutamide, coffee, vitamin D3, and PROSTVAC. We found that administration of 5-ARIs was associated with improved progression-free survival (PFS; hazard ratio: 0.59; 95% confidence interval 0.48-0.72), with no increased toxicity signals. Therapies such as vitamin D3, chlormadinone, FT, and enzalutamide have shown some efficacy. However, these anticancer drugs have been associated with treatment-related adverse events in up to 88% of patients.
    CONCLUSIONS: The use of 5-ARIs in PCa patients on AS is associated with longer PFS. However, for the other interventions, it is difficult to draw clear conclusions based on the weak available evidence.
    RESULTS: Patients with prostate cancer managed with active surveillance (AS) who are treated with 5-alpha reductase inhibitors have a lower risk of disease progression, with minimal adverse events. Other interventions require more studies to determine their efficacy and safety profile in men on AS.
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  • 文章类型: Case Reports
    血精症是一种常见的,而是引发焦虑的泌尿生殖系统疾病.在没有自发解决的情况下,用5-α还原酶抑制剂进行药物干预已被证明是成功的.在难治性血精症的情况下,机器人辅助腹腔镜精囊切除术可提供明确的治疗选择.在保守治疗失败后,对一名42岁的男性进行了机器人辅助的双侧精囊切除术,患有难治性无痛性血精症。术后三个月,患者报告6次射精后出现血精消退,但对勃起功能无影响.机器人辅助方法是安全可行的,具有良好的功能效果和降低的发病率。
    Hematospermia is a common, but anxiety-provoking genitourinary condition. In instances without spontaneous resolution, pharmacologic intervention with a 5-alpha reductase inhibitor has been shown to be successful. In cases of refractory hematospermia, robotic-assisted laparoscopic seminal vesiculectomy may provide a definitive treatment option. A robotic-assisted bilateral seminal vesiculectomy was performed on a 42-year-old male with refractory painless hematospermia after failing conservative management. Three months post-operatively, the patient reported resolution of hematospermia after six ejaculations with no impact on erectile function. The robotic-assisted approach is safe and feasible with good functional outcomes and reduced morbidity.
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  • 文章类型: Journal Article
    背景:磁共振成像(MRI)扫描越来越多地成为可疑前列腺癌的一线检查,对活检的决定至关重要。已显示使用5-α还原酶抑制剂(5-ARI)可降低前列腺大小和前列腺癌风险。然而,关于5-ARI使用如何影响MRI结果和活检结果的数据不足.这项研究探讨了接受和未接受5-ARI治疗的患者在影像学和前列腺癌诊断方面的差异。
    方法:从2015年到2020年,我们收集了在一个中心接受前列腺活检的连续患者的回顾性数据。我们纳入了未进行活检的患者,之前有阴性活检,或积极监测低度前列腺癌。收集临床和病理资料,包括5-ARI使用,前列腺成像报告和数据系统(PIRADS)分类和活检结果。
    结果:351名男性接受了有或没有靶向活检的饱和活检。54人(15.3%)有5-ARI使用史。在MPMRI上,5ARI组和非5-ARI组之间在PIRADS分布上没有显着差异,病变的数量,和病变位置。在5-ARI组中检测到的癌症明显减少(46.3%vs.68.0%;p<0.01)。活检阳性和阴性的5-ARI患者中PIRADS分布差异无统计学意义。
    结论:我们的研究发现生化,5-ARI和非5-ARI组的影像学和活检特征。虽然两组的PIRADS分布相似,5-ARI患者在所有PIRADS类别中活检阳性率较低,这可能表明使用5ARI可能会混淆MRI检查结果。应进一步研究5-ARI治疗如何影响前列腺癌的影像学特征。
    BACKGROUND: Magnetic resonance imaging (MRI) scans are increasingly first-line investigations for suspected prostate cancer, and essential in the decision for biopsy. 5-alpha reductase inhibitor (5-ARI) use has been shown to reduce prostate size and prostate cancer risk. However, insufficient data exists on how 5-ARI use affects MRI findings and yield of biopsy. This study explores the differences in imaging and prostate cancer diagnoses between patients receiving and not receiving 5-ARI therapy.
    METHODS: From 2015 to 2020, we collected retrospective data of consecutive patients undergoing prostate biopsy at one centre. We included patients who were biopsy-naïve, had prior negative biopsies, or on active surveillance for low-grade prostate cancer. Clinical and pathological data was collected, including 5-ARI use, Prostate Imaging Reporting and Data System (PIRADS) classification and biopsy results.
    RESULTS: 351 men underwent saturation biopsy with or without targeted biopsies. 54 (15.3%) had a history of 5-ARI use. On mpMRI, there was no significant difference between the 5ARI and non-5-ARI groups in PIRADS distribution, number of lesions, and lesion location. Significantly fewer cancers were detected in the 5-ARI group (46.3% vs. 68.0%; p < 0.01). There were no significant differences in PIRADS distribution in 5-ARI patients with positive and negative biopsy.
    CONCLUSIONS: Our study found significant differences in biochemical, imaging and biopsy characteristics between 5-ARI and non-5-ARI groups. While both groups had similar PIRADS distribution, 5-ARI patients had a lower rate of positive biopsies across all PIRADS categories, which may suggest that the use of 5ARI may confound MRI findings. Further studies on how 5-ARI therapy affects the imaging characteristics of prostate cancer should be performed.
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  • 文章类型: Journal Article
    目的:5-α还原酶抑制剂(5ARI)可将前列腺特异性抗原(PSA)降低一半,但其对前列腺健康指数(phi)的影响尚不清楚。这项研究旨在研究这种影响,并能够准确解释PSA升高和5ARI患者的phi。
    方法:这是一项前瞻性研究,评估非那雄胺对PSA的影响,游离PSA(fPSA)[-2]PSA为4-20ng/mL的男性中6个和12个月的proPSA(p2PSA)和phi,没有事先使用5ARI,招募前6个月内1例前列腺活检阴性。如果基线时国际前列腺症状评分(IPSS)≥8分,则提供5ARI非那雄胺(5mg/天)1年。5ARI组包括服用非那雄胺的患者,而对照组包括未服用非那雄胺的患者。在基线和不同时间点之间以及在1年时在各组之间使用t检验比较血液结果。
    结果:164名男性符合纳入标准,150名男性被分析。5ARI组(n=100)1年,平均PSA从8.9(±SD3.7)下降51.4%至4.4(±SD2.8)ng/mL(配对t检验,p<0.001),fPSA从1.6(±0.6)纳克/毫升降至0.8(±0.4)纳克/毫升降低52.4%(p<0.001),p2PSA从18.4(±8.8)到8.3(±5.6)pg/mL降低了55.3%(p<0.001),phi从33.7(±11.9)降至22.4(±12.5)(p<0.001),下降了34.2%。对照组的PSA和phi值在1年内保持不变,并显着高于5ARI组。
    结论:这项研究表明,在5ARI的男性中,p2PSA和phi分别降低了约55%和34%。非那雄胺男性的phi需要除以0.66的转换因子,以允许5ARI男性的phi解释和使用。
    OBJECTIVE: 5-alpha reductase inhibitor (5ARI) reduces prostate-specific antigen (PSA) by half but its effect on prostate health index (phi) is unknown. This study aims to investigate this effect and to enable accurate interpretation of phi in men with elevated PSA and on 5ARI.
    METHODS: This is a prospective study evaluating the effect of finasteride on PSA, free PSA (fPSA), [ - 2]proPSA (p2PSA) and phi at 6 and 12 moths in men with PSA 4-20 ng/mL, no prior 5ARI use, and one negative prostate biopsy within 6 months before recruitment. The 5ARI Finasteride (5 mg/day) for 1 year was offered if International Prostatic Symptom Score (IPSS) was ≥ 8 at baseline. 5ARI group included patients taking finasteride, while control group included patients not on finasteride. The blood results were compared with t-test between baseline and different time points in each group and between groups at 1 year.
    RESULTS: 164 men fit the inclusion criteria and 150 were analyzed. In 5ARI group (n = 100) at 1 year, mean PSA reduced by 51.4% from 8.9(± SD 3.7) to 4.4(± SD 2.8)ng/mL (paired t-test, p < 0.001), fPSA reduced by 52.4% from 1.6(± 0.6) to 0.8(± 0.4)ng/mL (p < 0.001), p2PSA reduced by 55.3% from 18.4(± 8.8) to 8.3(± 5.6)pg/mL (p < 0.001), and phi reduced by 34.2% from 33.7(± 11.9) to 22.4(± 12.5) (p < 0.001). PSA and phi values in the control group remained static over 1 year and significantly higher than those in 5ARI group.
    CONCLUSIONS: This study demonstrated p2PSA and phi are reduced by about 55% and 34% in men on 5ARI. A conversion factor of division by 0.66 is needed for phi in men on finasteride to allow the interpretation and use of phi in men on 5ARI.
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  • 文章类型: Journal Article
    良性前列腺增生(BPH)是老年男性常见的尿道周围前列腺组织的进行性扩张。前列腺肥大的患者用5-α还原酶抑制剂(5ARIs)治疗,通过阻断睾酮向二氢睾酮(DHT)的转化来缩小前列腺体积。DHT水平的降低可引起前列腺分泌腔细胞的萎缩和凋亡,这导致以改善下尿路症状为特征的良好临床反应。然而,5ARI治疗的组织学反应在整个前列腺腺泡中通常是不均匀的,下尿路症状可能持续需要手术干预.我们使用两种空间分析方法来表征5ARI治疗男性前列腺组织学正常和萎缩区域的基因表达变化。使用Visium空间基因表达平台进行客观转录组学分析显示,5ARI诱导的前列腺腔细胞萎缩与雄激素受体信号传导降低和包括LTF在内的尿道俱乐部细胞基因表达增加相关,PIGR,OLFM4、SCGB1A1和SCGB3A1。通过增加NF-κB信号和抗凋亡BCL2表达,萎缩腺泡内的前列腺腔细胞适应DHT降低的条件,这可以解释他们的生存。使用带有探针集的GeoMx数字空间分析来评估约18000RNA靶标,我们证实,与具有NKX3-1表达的组织学正常腺泡相比,表达SCGB3A1的萎缩腺泡显示更高水平的俱乐部细胞标志物。此外,5ARI诱导的萎缩区域内的俱乐部样细胞与前列腺尿道的真正俱乐部细胞非常相似。比较5ARI治疗的男性的组织学正常区域和未经治疗的男性的组织学正常区域,发现转录差异很小。一起来看,我们的结果描述了对5ARI治疗的异质性反应,其中萎缩腺泡中的细胞在对5ARI治疗的反应中经历了从前列腺分泌腔到俱乐部细胞样状态的适应.©2021英国和爱尔兰病理学会。
    Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.
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  • 文章类型: Journal Article
    Primum non nocere. As physicians, our goal is to treat illnesses and alleviate suffering; however, in doing so, we can generate new problems in a game of medical whack-a-mole. For some patients, certain consequences or side effects are tolerable, while others may believe they have no alternative. For a male patient with infertility, a thorough history is imperative to elucidate whether the patient has been or is currently being exposed to medications that will harm libido, spermatogenesis, ejaculation, or the hypothalamic-pituitary-testosterone axis. This article will review the most common medications causing iatrogenic male infertility as well as options to minimize or even reverse their impact.
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  • 文章类型: Journal Article
    OBJECTIVE: To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer.
    METHODS: We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan-Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value < 0.05 was considered statistically significant.
    RESULTS: Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0-17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA > 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p < 0.001; p < 0.001), respectively. The main limitation is the retrospective study design.
    CONCLUSIONS: 5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.
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  • 文章类型: Journal Article
    OBJECTIVE: Freedom from medication is a common goal for patients undergoing surgical treatment of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS). Knowing medication discontinuation rates following various forms of transurethral prostatectomy may aid patient counseling and assessing the comparative effectiveness of different approaches. This review examined discontinuation rates of BPH/LUTS medications following transurethral prostatectomy.
    RESULTS: Rates of BPH/LUTS medication use after transurethral resection of the prostate varied from 15% to 55%, and discontinuation rates were 54-95% across medications and follow-up periods. For laser prostatectomy, approximately 18% of patients continued medications postoperatively and discontinuation rates ranged from 53% to 75%. Minimal data on holmium laser enucleation existed. For reference, medication discontinuation rates after transurethral needle ablation or microwave therapy were only 15-28%. No recommendations or best practices inform the use of medical therapy following BPH surgery. Rates of BPH/LUTS medication use following transurethral prostatectomy are considerable.
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  • 文章类型: Journal Article
    背景:雄激素性脱发(AGA)是一种经常遇到的皮肤病学问题,会影响患者的自尊和生活质量。非那雄胺是一种选择性的5-α还原酶抑制剂,已被批准用于治疗男性AGA和女性型脱发(FPHL)的标签外使用;然而,其不利影响可能会限制其使用。局部非那雄胺是一种旨在减少口服给药引起的并发症的新制剂。目的:这篇综述评估了药理学,目前的治疗用途,以及局部非那雄胺治疗AGA和FPHL的安全性。方法:从1992年1月至2020年1月,进行了PubMed搜索,以包括所有关于非那雄胺的英语文章。结果:共纳入33篇文献,其中非那雄胺相关文献28篇,AGA相关文献5篇。关于局部非那雄胺治疗男性AGA和FPHL的多项研究显示出积极的结果,具有良好的安全性。结论:局部非那雄胺是一种有前途的治疗选择。我们强调持续研究对于建立新型治疗剂的重要性。
    Background: Androgenetic alopecia (AGA) is a frequently encountered dermatological concern that impacts a patient\'s self-esteem and quality of life. Finasteride is a selective 5-alpha reductase inhibitor that has been approved for the treatment of male AGA and the off-label use in female pattern hair loss (FPHL); however, its adverse effects may limit its use. Topical finasteride is a new formulation that aims to decrease complications caused by oral administration.Objective: This review assesses the pharmacology, current therapeutic use, and safety of topical finasteride for the treatment of AGA and FPHL.Methods: A PubMed search was conducted to include all English language articles on topical finasteride from January 1992 to January 2020.Results: A total of 33 articles including 28 topical finasteride related articles and five AGA related articles were included in this review. Multiple studies on topical finasteride as the treatment for male AGA and FPHL showed positive results with a favorable safety profile.Conclusions: Topical finasteride is a promising therapeutic option. We emphasize the importance of continued research for the establishment of a novel therapeutic agent.
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