非那雄胺对老年单纯收缩期高血压合并良性前列腺增生患者的疗效及安全性

目的：分析应用非那雄胺对老年单纯收缩期高血压（ISH）合并良性前列腺增生（BPH）患者的疗效及安全性。方法：选择84例2011年6月至2013年5月我院的ISH合并BPH老年患者,依据给药方案不同分为：非那雄胺组（44例）;常规治疗组（40例,行常规治疗不使用非那雄胺）。疗程均为半年,比较两组国际前列腺症状评分（IPSS）、生活质量评分（QOL）,前列腺特异性抗原（PSA）、急性尿潴留发生率、最大尿流率（Qmax）、膀胱残余尿量（PRV）、前列腺体积（PV）以及不良反应发生率。结果：与常规治疗组相比,非那雄胺组的 IPSS 评分[（13.2±2.4）分比（9.4±1.1）分]、PRV [（21.4±4.6）ml比（9.0±2.3）ml]、PV [（36.8±3.8）ml比（29.5±3.0）ml]、PSA [（2.45±0.74）μg/L比（1.26±0.48）μg/L]及急性尿潴留发生率（17.50％比9.09％）显著降低（P＜0.05或＜0.01）,而 Qmax [（10.2±2.4）ml比（13.7±3.8）ml]及 QOL评分[（3.1±1.0）分比（4.7±1.5）分]则显著升高（P＜0.05）。两组各项不良反应发生率无统计学差异（P 均＞0.05）。结论：单纯收缩期高血压合并良性前列腺增生老年患者应用非那雄胺的疗效显著,且不良反应未显著增加。     

夏荔芪胶囊联合非那雄胺治疗良性前列腺增生症的临床研究

目的探讨夏荔芪胶囊联合非那雄胺片治疗良性前列腺增生症的临床疗效。方法选取2017年10月—2019年1月首都医科大学附属北京康复医院收治的100例良性前列腺增生症患者为研究对象,将全部患者按照随机数字表法分为对照组和治疗组,每组各50例。对照组口服非那雄胺片,5mg/次,1次/d。治疗组在对照组治疗的基础上口服夏荔芪胶囊,3粒/次,3次/d。两组患者连续治疗12周。观察两组的临床疗效,比较两组国际前列腺症状评分表(I-PSS)评分、前列腺体积、残余尿量、尿流率、细胞因子水平、生活质量。结果治疗后,对照组和治疗组的总有效率分别为80.00%、94.00%,两组比较差异有统计学意义(P0.05)。治疗后,两组的I-PSS评分、前列腺体积、残余尿量均显著降低,尿流率显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗后,治疗组的I-PSS评分、前列腺体积、残余尿量均低于对照组,尿流率高于对照组,差异有统计学意义(P0.05)。治疗后,两组的白细胞介素-17(IL-17)、前列腺素E2(PGE2)、前列腺特异抗原(PSA)、高敏C反应蛋白(hs-CRP)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗后,治疗组的IL-17、PGE2、PSA、hs-CRP水平明显低于对照组,差异有统计学意义(P0.05)。治疗后,两组的生活质量量表(QOL)评分显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗后,治疗组的QOL评分比对照组低,差异有统计学意义(P0.05)。结论夏荔芪胶囊联合非那雄胺片治疗良性前列腺增生症具有较好的临床疗效,可改善临床症状和生活质量,减轻炎症反应,具有一定的临床推广应用价值。     

Combined Sabal and Urtica extract vs finasteride in BPH (Alken stage I–II)

Summary Therapeutic equivalence should be demonstrated in a randomised, reference-controlled multicentric double blind clinical trial with PRO 160/120, a combination of Sabal- and Urtica-Extract, and Finasteride, respectively, in patients suffering from benign prostatic hyperplasia (BPH, Stage I to II according to Alken). The study involved 543 patients, who were treated for 48 weeks with two capsules of PRO 160/120 or one capsule of Finasteride per day, in a double dummy design. Primary variable was the change of the maximum urinary flow after 24 weeks of therapy in comparison to therapy start. As secondary variables urodynamic parameters such as average urinary flow, miction volume and miction time were monitored. Urinary symptoms were recorded by the International-Prostate-Symptom-Score (I-PSS, Paris 1993). Additionally, the impacts of the symptoms on quality of life had been assessed by a quality of life questionnaire according to The American Urological Association Measurement Committee (1991) [9]. An increase of the urinary flow rate could be observed in both treatment groups (1,9 ml/s with PRO 160/120; 2,4 ml/s with Finasteride). During the trial, the average urinary flow increased, whereas the miction time decreased in both groups in a similar extent. The miction volume did not show any relevant differences after treatment with either PRO 160/120 or Finasteride. The I-PSS decreased from 11.3 at the therapy start to 8.2 after 24 weeks and 6.5 (week 48) under PRO 160/120 and from 11.8 to 8.0 and 6.2, under Finasteride, respectively. Accordingly, life quality improved between therapy start and therapy end from 7.5 to 4.3 with PRO 160/120 and from 7.7 to 4.1 with Finasteride. In terms of safety aspects less adverse events occured with the Sabal/Urtica-Extract as with Finasteride. Especially less cases of diminished ejaculation volume, erectile dysfunction and headache have been reported.      

The Benefits of Dual Inhibition of 5α Reductase

In humans, androgens balance cell proliferation and apoptosis, ensuring normal growth and development of the prostate, but also driving pathologic gland enlargement in benign prostatic hyperplasia (BPH) and prostate cancer. The two main androgens are testosterone and dihydrotestosterone (DHT). Reducing testosterone levels results in significant sexual side-effects, whereas reducing DHT does not result in any major safety or tolerability issues. DHT is synthesised from testosterone by the 5α-reductase enzyme, of which there are two isozymes, type I and type II. Expression of both of these isozymes is increased in BPH. Two 5α-reductase inhibitors (5ARIs) are available for BPH management; the dual inhibitor dutasteride inhibits type I and type II 5α reductase, whereas finasteride inhibits only the type II isoenzyme. Pharmacologic studies indicate that the dual 5ARI dutasteride results in greater suppression of DHT than the type II inhibitor. A phase 2, double-blind, placebo-controlled study conducted in men with BPH demonstrated that maximal DHT suppression is achieved in a larger proportion of patients with dutasteride than with finasteride. Dutasteride demonstrates sustained improvement in symptom score and maximal flow rate with no increase in prostate volume up to 4 yr.     

非那雄胺在经尿道前列腺电切术后镜下血尿阴转中的作用

目的:探讨非那雄胺在经尿道前列腺电切术后镜下血尿阴转中的作用。方法:追踪随访经尿道前列腺电切术后镜下血尿患者468例,根据对血尿的治疗方法不同随机分成两组:治疗组230例,术后第1日开始口服非那雄胺5mg/d,其他治疗与对照组相同;对照组238例,术后第1日开始予抗感染、止血及对症等治疗。结果:治疗组镜下血尿阴转时间24～38日,平均32日,对照组相应为33～67日,平均46日(P<0.01);治疗组术后4周镜下血尿阴转率70%、5周为95%、6周为100%,对照组相应为5%、8%、48%,在各时段镜下血尿阴转率两组差异有统计学意义,P<0.01。结论:非那雄胺能明显缩短前列腺电切术后镜下血尿阴转时间,减少术后出血。     

Evaluation of the efficacy and toxicity of oral and topical pumpkin oil on the hair growth of mice

This study aimed to evaluate the efficacy and safety of a topical and oral administration of pumpkin seed oil (PSO) on the hair growth of BALB/c male mice. The animals had their dorsal area shaved (2 ×2 cm) and they were divided into 6 experimental groups. They received orally saline (OS), finasteride (F), or PSO (OP) for 14 days; or topically saline (TS), minoxidil (M), or PSO (TP) for 7 days. The euthanasia of all of the mice occurred on the 22nd day, and the histological slides from the skin area were analyzed. Lipoperoxidation in the liver was assessed through the TBARS method and was also evaluated by the antioxidant enzymes (SOD and CAT). The comet assay and the micronucleus tests were performed for genotoxic/mutagenic safety analyses. A significant increase in the number of hair follicles in the TP group was seen (8.8 ± 0.8) but it was disorganized, with loose dermal collagen. Finasteride presented a significant increase in the levels of the TBARS, SOD, and CAT in the liver, and M increased the DNA damage in the blood and the liver tissues. PSO did not induce any significant changes. In addition, PSO did not induce genotoxic or mutagenic effects. In conclusion, the oral PSO for 14 days acted in the proliferation of the hair follicles, without toxicity signals in the liver.Data availabilityThe authors confirm that all of the relevant data is included in the article and/or in the supplementary information file.     

Six weeks finasteride monotherapy before TURP: Does it improve quality of life in early post operative period?

Introduction

Benign prostatic hyperplasia (BPH) is a common disease affecting men 50 years and older. Treatment options consist of observation, pharmacological treatment, minimally invasive surgery and traditional surgery. Alpha-blockers and 5-alpha-reductase inhibitors are the primary medications used to treat BPH. Transurethral resection of the prostate (TURP) is the gold standard of surgical management of BPH.

特拉唑嗪、非那司提和坦素罗辛治疗良性前列腺增生症的有效性评价

目的评价和比较特拉唑嗪、非那司提和坦素罗辛,以及其中任意两药联用与单药治疗良性前列腺增生症(benign prostatic hyperplasia,BPH)的有效性.方法计算机检索MEDLINE(1966～2004.12)、EMBASE(1984～2004.12)、Cochrane图书馆(2004年第4期)、美国<生物学文摘>光盘数据库(1990～2004.12)和中国生物医学文献光盘数据库(1978～2004.12)等,手检10种相关杂志.纳入与有效性有关的随机对照试验(RCT)和半随机对照试验(CCT),并追索已纳入文献的参考文献.由至少两位系统评价员独立进行文献筛查、质量评价和资料提取,并交叉核对,不同意见请第三者裁决.采用RevMan 4.2软件进行Meta分析.结果共初检出656篇文献,经筛选后最后纳入12篇原始研究(2 471例)进行分析,包括11篇RCT,1篇CCT.Meta分析结果显示:与特拉唑嗪比较,坦素罗辛改善国际前列腺症状评分(international prostatic symptom score, IPSS)更明显[WMD＝0.75,95%CI (0.03,1.46),P=0.04],差异有统计学意义,但在平均尿流率(average rate of urine flow, AFR)改善程度 [WMD=0.23,95%CI (-0.39,0.85),P=0.46]、残余尿量改善程度 [WMD=0.82,95%CI (-2.92,4.57),P=0.67] 以及减小前列腺体积的效果 [WMD=2.20,95%CI (-3.99,8.39),P=0.49] 方面,两者差异均无统计学意义.非那司提与坦素罗辛比较,两者在改善IPSS [WMD=0.65,95%CI (-0.45,1.75),P=0.25] 和最大尿流率方面 [WMD=0.39,95%CI (-0.72,1.51),P=0.49],其差异均无统计学意义.仅有两个研究比较了非那司提与特拉唑嗪对最大尿流率的影响,且结论各异.仅有1个研究(538例)比较了单用非那司提、特拉唑嗪与联用非那司提和特拉唑嗪治疗良性前列腺增生症的有效率,结果显示两药联用的有效率明显优于单用非那司提,但与单用特拉唑嗪无明显差异.结论非那司提、特拉唑嗪和坦素罗辛治疗良性前列腺增生症的效果差别不大.在改善IPSS和生活质量方面,坦素罗辛似乎优于特拉唑嗪;非那司提与特拉唑嗪联用比单用非那司提有效率高,但不比单用特拉唑嗪效果好.结合安全性和经济性考虑,推荐临床短期单用坦素罗辛治疗良性前列腺增生症.长期治疗方案目前尚无足够的证据支持,有待进一步研究;在新证据产生之前不推荐联合用药.鉴于有关临床研究现状,呼吁提高国内外原始研究质量,增大样本量,开展高质量临床研究.     

非那雄胺对经尿道前列腺等离子电切除术中、术后各项指标的影响

目的探讨术前服用非那雄胺对经尿道前列腺等离子电切除术（TUPKVP）患者国际前列腺症状评分（IPSS）、生活质量评分（QOL）、最大尿流速（Qmax）、残余尿量（PVR）、术中出血、手术时间、冲洗液量等指标的影响。方法180例前列腺增生症患者随机分为观察组和对照组各90例,观察组和对照组均采用常规治疗,观察组术前1周开始每天服用非那雄胺5mg;对照组术前未服用非那雄胺。术后随访1个月,比较两组TUPKVP患者IPSS、QOL、Qmax、PVR、术中失血量、手术时间、冲洗液量等指标变化。结果治疗后,两组均较治疗前有显著改善（t：5．11、7．01、3．06、6．17、11．82、4．13、4．52、5．17,均P〈0．05）;其中IPSS、Qmax、PVR治疗后观察组显著优于对照组（t=11．35、5．26、3．12,均P〈0．05）,QOL治疗后两组差异无统计学意义（P〉0．05）;观察组治愈率87．8％,明显高于对照组（X2=14．56,P〈0．05）;观察组术中出血、手术时间、冲洗液量均优于对照组（t=21．15、43．12、5．33,均P〈0．05）,两组住院时间差异无统计学意义（P〉0．05）。结论术前服用非那雄胺能够减少TUPKVP术中出血及冲洗液量,缩短手术时间,有效提高经尿道等离子电切前列腺术的临床效果。     

Finasteride Increases the Expression of Hemoxygenase-1 (HO-1) and NF-E2-Related Factor-2 (Nrf2) Proteins in PC-3 Cells: Implication of Finasteride-Mediated High-Grade Prostate Tumor Occurrence

A number of naturally-occurring or synthetic chemicals have been reported to exhibit prostate chemopreventive effects. Synthetic 5α-reductase (5-AR) inhibitors, e.g. finasteride and durasteride, gained special interests as possible prostate chemopreventive agents. Indeed, two large-scale epidemiological studies have demonstrated that finasteride or durasteride significantly reduced the incidence of prostate cancer formation in men. However, these studies have raised an unexpected concern; finasteride and durasteride increased the occurrence of aggressive prostate tumor formation. In the present study, we have observed that treatment of finasteride did not affect the growth of androgen-refractory PC-3 prostate cancer cells. Finasteride also failed to induce apoptosis or affect the expression of proto-oncogenes in PC-3 cells. Interestingly, we found that treatment of finasteride induced the expression of Nrf2 and HO-1 proteins in PC-3 cells. In particular, basal level of Nrf2 protein was higher in androgen-refractory prostate cancer cells, e.g. DU-145 and PC-3 cells, compared with androgen-responsive prostate cancer cells, e.g. LNCaP cells. Also, treatment of finasteride resulted in a selective induction of Nrf2 protein in DU-145 and PC-3 cells, but not in LNCaP cells. In view of the fact that upregulation of Nrf2-mediated phase II cytoprotective enzymes contribute to attenuating tumor promotion in normal cells, but, on the other hand, confers a selective advantage for cancer cells to proliferate and survive against chemical carcinogenesis and other forms of toxicity, we propose that finasteride-mediated induction of Nrf2 protein might be responsible, at least in part, for an increased risk of high-grade prostate tumor formation in men.