他达拉非对下尿路症状伴勃起功能障碍的疗效研究
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摘要
目的:探讨小剂量他达拉非对BPH所致下尿路症状(LUTS)合并ED患者的治疗效果。方法:收集BPH所致LUTS合并ED的患者126例,随机分为治疗Ⅰ组、治疗Ⅱ组、对照组,每组42例。治疗Ⅰ组每日口服他达拉非5 mg+盐酸坦索罗辛缓释胶囊0.2 mg,共12周;治疗Ⅱ组每日口服他达拉非5 mg,共12周;对照组每日服用安慰剂,共12周。在基线时、治疗6周、治疗12周、治疗停药4周、治疗停药8周共5个时间点接受随访,并在每个时间点记录研究对象的排尿期症状亚项评分、储尿期症状亚项评分、IPSS总评分及IIEF-5评分,并嘱患者记录研究期间性生活次数。结果:针对排尿期症状亚项评分:治疗Ⅰ组5个时间点间两两比较差异均有统计学意义(P<0.05);治疗Ⅱ组中治疗6周与基线、治疗停药8周与基线、治疗停药8周与治疗6周比较差异无统计学意义(P均>0.05);对照组5个时间点差异无统计学意义(P>0.05)。治疗6周时、治疗停药8周时治疗Ⅱ组与对照组比较差异无统计学意义(P均>0.05);治疗12周、治疗停药4周时3组间两两比较均有统计学意义(P<0.05)。针对储尿期症状亚项评分:治疗Ⅰ组、治疗Ⅱ组5个时间点间两两比较差异均有统计学意义(P<0.05);对照组5个时间点差异无统计学意义(P>0.05)。治疗6周时、治疗12周时、治疗停药4周时、治疗停药8周时治疗Ⅰ组与治疗Ⅱ组比较差异均无统计学意义(P均>0.05)。针对IPSS总评分:治疗Ⅰ组、治疗Ⅱ组中治疗停药8周与治疗6周比较差异无统计学意义(P均>0.05);对照组5个时间点差异无统计学意义(P>0.05)。治疗6周时、治疗12周时、治疗停药4周时、治疗停药8周时3组间两两比较均有统计学意义(P<0.05)。针对IIEF-5评分:3组随访期间性生活次数比较差异无统计学意义(P>0.05);治疗Ⅰ组中治疗停药4周与治疗6周、治疗停药8周与治疗6周、治疗停药8周与治疗停药4周比较差异无统计学意义(P均>0.05);治疗Ⅱ组中治疗停药8周与治疗6周比较差异无统计学意义(P>0.05);对照组5个时间点差异无统计学意义(P>0.05)。治疗12周时、治疗停药4周时治疗Ⅰ组与治疗Ⅱ组比较差异无统计学意义(P均>0.05);治疗6周时、治疗停药8周时3组间两两比较均有统计学意义(P<0.05)。结论:每日单用他达拉非5 mg对改善患者储尿期症状亚项评分、IIEF-5评分具有良好效果,且此疗效与联合用药方案效果相似,在停药后仍具有延续性,可推荐用于ED伴以储尿期症状为主的BPH/LUTS患者。
Objective: To investigate the therapeutic effect of low-dose tadalafil on BPH-induced lower urinary tract symptoms(LUTS) complicated with ED. Methods: We randomly assigned 126 patients with BPH-induced LUTS and ED to receive daily administration of tadalafil(5 mg) plus tamsulosin hydrochloride sustained-release capsules(0.2 mg)(treatment group Ⅰ [T-Ⅰ], n = 42), tadalafil(5 mg) only(treatment group Ⅱ [T-Ⅱ], n = 42) or placebo(control group, n = 42), all for 12 weeks. Before and after 6 and 12 weeks of medication, and at 4 and 8 weeks after drug withdrawal, we recorded and compared the IPSS sub-item scores in the voiding stage and urinary storage symptoms, total IPSS, IIEF-5 scores, and the frequency of sexual activities among the three groups of patients. Results: As for the IPSS sub-item scores in the voiding stage symptoms, T-Ⅰ showed statistically significant differences between any two of the five time points(P < 0.05), but not T-Ⅱ between the baseline and 6-week medication or 8-week withdrawal(P > 0.05), or between 6-week medication and 8-week withdrawal(P > 0.05), nor did the control group among the five time points(P > 0.05). Statistically significant differences were observed between any two of the three groups at 12 weeks of medication and 4 weeks after drug withdrawal(P < 0.05), but not between the T-Ⅱ and control groups at 6 weeks of medication or 8 weeks after withdrawal(P > 0.05). As to the IPSS sub-item scores in the urinary storage symptoms, there were significant differences between any two time points in T-Ⅰ and T-Ⅱ(P < 0.05), but not in the control(P > 0.05), nor between T-Ⅰ and T-Ⅱ at 6 or 12 weeks of medication or at 4 or 8 weeks after drug withdrawal(P > 0.05). With regard to the total IPSS, statistically significant differences were found between any two of the three groups at 6 and 12 weeks of medication and 4 and 8 weeks after drug withdrawal(P < 0.05), but not between 6-week medication and 8-week withdrawal in T-Ⅰ or T-Ⅱ(P > 0.05), nor among the five time points in the control group(P > 0.05). Concerning the IIEF-5 scores, there was no significant difference in the frequency of sexual activities between the three groups(P>0.05).There were statistically significant differences between any two of the three groups at 6 weeks of medication and 8 weeks after drug withdrawal(P<0.05), but not between 6-week medication and 4-or 8-week withdrawal(P > 0.05) or between 4-and 8-week withdrawal(P > 0.05) in T-Ⅰ, nor between 6-week medication and 8-week withdrawal in T-Ⅱ(P > 0.05) or among the five time points in the control(P > 0.05), nor between T-Ⅰ and T-Ⅱ at 12 weeks of medication(P > 0.05) or 4 weeks after drug withdrawal(P > 0.05). Conclusion: Daily administration of tadalafil at 5 mg can effectively improve the IPSS sub-item scores in the urinary storage symptoms and IIEF-5 scores, with a persistent effect after withdrawal similar to that of its combination with other drugs, and therefore can be recommended for the treatment of BPH-induced LUTS complicated with ED. Natl J Androl, 2019, 25(6): 514-521
Objective: To investigate the therapeutic effect of low-dose tadalafil on BPH-induced lower urinary tract symptoms(LUTS) complicated with ED. Methods: We randomly assigned 126 patients with BPH-induced LUTS and ED to receive daily administration of tadalafil(5 mg) plus tamsulosin hydrochloride sustained-release capsules(0.2 mg)(treatment group Ⅰ [T-Ⅰ], n = 42), tadalafil(5 mg) only(treatment group Ⅱ [T-Ⅱ], n = 42) or placebo(control group, n = 42), all for 12 weeks. Before and after 6 and 12 weeks of medication, and at 4 and 8 weeks after drug withdrawal, we recorded and compared the IPSS sub-item scores in the voiding stage and urinary storage symptoms, total IPSS, IIEF-5 scores, and the frequency of sexual activities among the three groups of patients. Results: As for the IPSS sub-item scores in the voiding stage symptoms, T-Ⅰ showed statistically significant differences between any two of the five time points(P < 0.05), but not T-Ⅱ between the baseline and 6-week medication or 8-week withdrawal(P > 0.05), or between 6-week medication and 8-week withdrawal(P > 0.05), nor did the control group among the five time points(P > 0.05). Statistically significant differences were observed between any two of the three groups at 12 weeks of medication and 4 weeks after drug withdrawal(P < 0.05), but not between the T-Ⅱ and control groups at 6 weeks of medication or 8 weeks after withdrawal(P > 0.05). As to the IPSS sub-item scores in the urinary storage symptoms, there were significant differences between any two time points in T-Ⅰ and T-Ⅱ(P < 0.05), but not in the control(P > 0.05), nor between T-Ⅰ and T-Ⅱ at 6 or 12 weeks of medication or at 4 or 8 weeks after drug withdrawal(P > 0.05). With regard to the total IPSS, statistically significant differences were found between any two of the three groups at 6 and 12 weeks of medication and 4 and 8 weeks after drug withdrawal(P < 0.05), but not between 6-week medication and 8-week withdrawal in T-Ⅰ or T-Ⅱ(P > 0.05), nor among the five time points in the control group(P > 0.05). Concerning the IIEF-5 scores, there was no significant difference in the frequency of sexual activities between the three groups(P>0.05).There were statistically significant differences between any two of the three groups at 6 weeks of medication and 8 weeks after drug withdrawal(P<0.05), but not between 6-week medication and 4-or 8-week withdrawal(P > 0.05) or between 4-and 8-week withdrawal(P > 0.05) in T-Ⅰ, nor between 6-week medication and 8-week withdrawal in T-Ⅱ(P > 0.05) or among the five time points in the control(P > 0.05), nor between T-Ⅰ and T-Ⅱ at 12 weeks of medication(P > 0.05) or 4 weeks after drug withdrawal(P > 0.05). Conclusion: Daily administration of tadalafil at 5 mg can effectively improve the IPSS sub-item scores in the urinary storage symptoms and IIEF-5 scores, with a persistent effect after withdrawal similar to that of its combination with other drugs, and therefore can be recommended for the treatment of BPH-induced LUTS complicated with ED. Natl J Androl, 2019, 25(6): 514-521
引文
[1] Abrams P,Cardozo L,Fall M,et al.The standardization of terminology in lower urinary tract function:Report from the standardization sub-committee of the International Continence Society.Urology,2003,61(1):37-49.
[2] Oelke M,Bachmann A,Descazeaud A,et al.EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction.Eur Urol,2013,64(1):118-140.
[3] McVary KT.Lower urinary tract symptoms and sexual dysfunction:Epidemiology and pathophysiology.BJU Int,2006,97(Suppl 2):23-28.
[4] Kohler TS,McVary KT.The relationship between erectile dysfunction and lower urinary tract symptoms and the role of phosphodiesterase type 5 inhibitors.Eur Urol,2009,55(1):38-48.
[5] 范宇.BPH与勃起功能障碍关系的研究进展.中华男科学杂志,2013,19(6):572-575.
[6] Martinez-Salamanca JI,Carballido J,Eardley I,et al.Phosphodiesterase type 5 inhibitors in the management of non-neurogenic male lower urinary tract symptoms:Critical analysis of current evidence.Eur Urol,2011,60(3):527-535.
[7] 袁润强.他达拉非治疗继发于良性前列腺增生下尿路症状的研究进展.中华男科学杂志,2012,18(12):1147-1151.
[8] McVary KT,Roehrborn CG,Avins AL,et al.Update on AUA guideline on the management of benign prostatic hyperplasia.J Urol,2011,185(5):1793-1803.
[9] Takahashi R,Miyazato M,Nishii H,et al.Tadalafil improves symptoms,erectile function and quality of life in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (KYU-PRO Study).Low Urin Tract Symptoms,2018,10(1):76-83.
[10] Mc Vary KT,Roehrborn CG,Kaminetsky JC,et al.Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia.J Urol,2007,177(4):1401-1407.
[11] Bechara A,Romano S,Casabe A,et al.Comparative efficacy assessment of tamsulosin vs tamsulosin plus tadalafil in the treatment of BPH/LUTS.Pilot study.J Sex Med,2008,5(9):2170-2178.
[12] Roehrborn CG,Mc Vary KT,Elion-Mboussa A,et al.Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia:A dose finding study.J Urol,2008,180(4):1228-1234.
[13] Roehrborn CG,Egan KB,Miner M,et al.Erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) combined responders to tadalafil after 12 weeks of treatment.BJU Int,2016,118(1):153-160.
[14] Roehrborn CG,Kaminetsky JC,Auerbach SM,et al.Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment.BJU Int,2010,105(4):502-507.
[15] Kim TB,Kim KH,Yoon SJ.Open-label,Intermittent dose,prospective study evaluating the effects of tadalafil on lower urinary tract symptoms and erectile function in patients with benign prostatic hyperplasia:Continuation and durability of effects.Int Neurourol J,2010,14(1):7-12.
[16] Porst H,Kim ED,Casabe AR,et al.Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia:Results of an international randomized,double-blind,placebo-controlled trial.Eur Urol,2011,60(5):1105-1113.
[17] Donatucci CF,Brock GB,Goldfischer ER,et al.Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia:A 1-year,open-label extension study.BJU Int,2011,107(7):1110-1116.
[18] Kim SW,Park NC,Lee SW,et al.Efficacy and safety of a fixed-dose combination therapy of tamsulosin and tadalafil for patients with lower urinary tract symptoms and erectile dysfunction:Results of a randomized,double-blinded,active-controlled trial.J Sex Med,2017,14(8):1018-1027.
[19] Oelke M,Giuliano F,Mirone V,et al.Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international,randomized,parallel,placebo-controlled clinical trial.Eur Urol,2012,61(5):917-925.
[20] Nishizawa O,Yoshida M,Takeda M,et al.Tadalafil 5 mg once daily for the treatment of Asian men with lower urinary tract symptoms secondary to benign prostatic hyperplasia:Analyses of data pooled from three randomized,double-blind,placebo-controlled studies.Int J Urol,2015,22(4):378-384.
[21] 陈洪德,叶雪挺,张奕荣,等.西地那非对兔膀胱出口部分梗阻模型膀胱顺应性及内皮素1的影响.中华医学杂志,2012,92(38):2720-2723.
[22] 陈洪德,叶雪挺,翁志梁,等.5型磷酸二酯酶抑制剂对大鼠不稳定膀胱的作用及其机制.中华医学杂志,2011,91(28):2001-2005.
[23] Rosen R,Altwein J,Boyle P,et al.Lower urinary tract symptoms and male sexual dysfunction:The multinational survey of the aging male (MSAM-7).Eur Urol,2003,44(6):637-649.
[24] Zhao C,Kim SH,Lee SW,et al.Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.BJU Int,2011,107(12):1943-1947.
[25] Koyama J,Kaiho Y,Kawasaki Y,et al.Penile blood pressure is useful to identify candidates for tadalafil treatment in patients with lower urinary tract symptoms.BJU Int,2019,123(1):124-129.
[26] Rosano GM,Aversa A,Vitale C,et al.Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk.Eur Urol,2005,47(2):214-222.
[27] Yoshinaga R,Kawai Y,Oka M,et al.Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release.Eur J Pharmacol,2015,754:92-97.
[28] Kawai Y,Oka M,Yoshinaga R,et al.Effects of the phosphodiesterase 5 inhibitor Tadalafil on bladder function in a rat model of partial bladder outlet obstruction.Neurourol Urodyn,2016,35(4):444-449.
[29] Maciejewski CC,Tredget EE,Metcalfe PD.Urodynamic improvements following oral medical therapy for partial bladder outlet obstruction in an animal model.Neurourol Urodyn,2015,34(3):286-291.
[30] Vignozzi L,Gacci M,Cellai I,et al.PDE5 inhibitors blunt inflammation in human BPH:A potential mechanism of action for PDE5 inhibitors in LUTS.Prostate,2013,73(13):1391-1402.
[31] Giuliano F,Uckert S,Maggi M,et al.The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia.Eur Urol,2013,63(3):506-516.
[32] Minagawa T,Aizawa N,Igawa Y,et al.Inhibitory effects of phosphodiesterase 5 inhibitor,tadalafil,on mechanosensitive bladder afferent nerve activities of the rat,and on acrolein-induced hyperactivity of these nerves.BJU Int,2012,110(6 Pt B):E259-E266.
[33] Singh DV,Mete UK,Mandal AK,et al.A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs.tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.J Sex Med,2014,11(1):187-196.
[34] 孙元明,顾卫东,吕坚伟,等.联合应用坦索罗辛和托特罗定治疗男性顽固性下尿路症状的临床研究.中华男科学杂志,2010,16(9):790-793.
[2] Oelke M,Bachmann A,Descazeaud A,et al.EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction.Eur Urol,2013,64(1):118-140.
[3] McVary KT.Lower urinary tract symptoms and sexual dysfunction:Epidemiology and pathophysiology.BJU Int,2006,97(Suppl 2):23-28.
[4] Kohler TS,McVary KT.The relationship between erectile dysfunction and lower urinary tract symptoms and the role of phosphodiesterase type 5 inhibitors.Eur Urol,2009,55(1):38-48.
[5] 范宇.BPH与勃起功能障碍关系的研究进展.中华男科学杂志,2013,19(6):572-575.
[6] Martinez-Salamanca JI,Carballido J,Eardley I,et al.Phosphodiesterase type 5 inhibitors in the management of non-neurogenic male lower urinary tract symptoms:Critical analysis of current evidence.Eur Urol,2011,60(3):527-535.
[7] 袁润强.他达拉非治疗继发于良性前列腺增生下尿路症状的研究进展.中华男科学杂志,2012,18(12):1147-1151.
[8] McVary KT,Roehrborn CG,Avins AL,et al.Update on AUA guideline on the management of benign prostatic hyperplasia.J Urol,2011,185(5):1793-1803.
[9] Takahashi R,Miyazato M,Nishii H,et al.Tadalafil improves symptoms,erectile function and quality of life in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (KYU-PRO Study).Low Urin Tract Symptoms,2018,10(1):76-83.
[10] Mc Vary KT,Roehrborn CG,Kaminetsky JC,et al.Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia.J Urol,2007,177(4):1401-1407.
[11] Bechara A,Romano S,Casabe A,et al.Comparative efficacy assessment of tamsulosin vs tamsulosin plus tadalafil in the treatment of BPH/LUTS.Pilot study.J Sex Med,2008,5(9):2170-2178.
[12] Roehrborn CG,Mc Vary KT,Elion-Mboussa A,et al.Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia:A dose finding study.J Urol,2008,180(4):1228-1234.
[13] Roehrborn CG,Egan KB,Miner M,et al.Erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) combined responders to tadalafil after 12 weeks of treatment.BJU Int,2016,118(1):153-160.
[14] Roehrborn CG,Kaminetsky JC,Auerbach SM,et al.Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment.BJU Int,2010,105(4):502-507.
[15] Kim TB,Kim KH,Yoon SJ.Open-label,Intermittent dose,prospective study evaluating the effects of tadalafil on lower urinary tract symptoms and erectile function in patients with benign prostatic hyperplasia:Continuation and durability of effects.Int Neurourol J,2010,14(1):7-12.
[16] Porst H,Kim ED,Casabe AR,et al.Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia:Results of an international randomized,double-blind,placebo-controlled trial.Eur Urol,2011,60(5):1105-1113.
[17] Donatucci CF,Brock GB,Goldfischer ER,et al.Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia:A 1-year,open-label extension study.BJU Int,2011,107(7):1110-1116.
[18] Kim SW,Park NC,Lee SW,et al.Efficacy and safety of a fixed-dose combination therapy of tamsulosin and tadalafil for patients with lower urinary tract symptoms and erectile dysfunction:Results of a randomized,double-blinded,active-controlled trial.J Sex Med,2017,14(8):1018-1027.
[19] Oelke M,Giuliano F,Mirone V,et al.Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international,randomized,parallel,placebo-controlled clinical trial.Eur Urol,2012,61(5):917-925.
[20] Nishizawa O,Yoshida M,Takeda M,et al.Tadalafil 5 mg once daily for the treatment of Asian men with lower urinary tract symptoms secondary to benign prostatic hyperplasia:Analyses of data pooled from three randomized,double-blind,placebo-controlled studies.Int J Urol,2015,22(4):378-384.
[21] 陈洪德,叶雪挺,张奕荣,等.西地那非对兔膀胱出口部分梗阻模型膀胱顺应性及内皮素1的影响.中华医学杂志,2012,92(38):2720-2723.
[22] 陈洪德,叶雪挺,翁志梁,等.5型磷酸二酯酶抑制剂对大鼠不稳定膀胱的作用及其机制.中华医学杂志,2011,91(28):2001-2005.
[23] Rosen R,Altwein J,Boyle P,et al.Lower urinary tract symptoms and male sexual dysfunction:The multinational survey of the aging male (MSAM-7).Eur Urol,2003,44(6):637-649.
[24] Zhao C,Kim SH,Lee SW,et al.Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.BJU Int,2011,107(12):1943-1947.
[25] Koyama J,Kaiho Y,Kawasaki Y,et al.Penile blood pressure is useful to identify candidates for tadalafil treatment in patients with lower urinary tract symptoms.BJU Int,2019,123(1):124-129.
[26] Rosano GM,Aversa A,Vitale C,et al.Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk.Eur Urol,2005,47(2):214-222.
[27] Yoshinaga R,Kawai Y,Oka M,et al.Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release.Eur J Pharmacol,2015,754:92-97.
[28] Kawai Y,Oka M,Yoshinaga R,et al.Effects of the phosphodiesterase 5 inhibitor Tadalafil on bladder function in a rat model of partial bladder outlet obstruction.Neurourol Urodyn,2016,35(4):444-449.
[29] Maciejewski CC,Tredget EE,Metcalfe PD.Urodynamic improvements following oral medical therapy for partial bladder outlet obstruction in an animal model.Neurourol Urodyn,2015,34(3):286-291.
[30] Vignozzi L,Gacci M,Cellai I,et al.PDE5 inhibitors blunt inflammation in human BPH:A potential mechanism of action for PDE5 inhibitors in LUTS.Prostate,2013,73(13):1391-1402.
[31] Giuliano F,Uckert S,Maggi M,et al.The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia.Eur Urol,2013,63(3):506-516.
[32] Minagawa T,Aizawa N,Igawa Y,et al.Inhibitory effects of phosphodiesterase 5 inhibitor,tadalafil,on mechanosensitive bladder afferent nerve activities of the rat,and on acrolein-induced hyperactivity of these nerves.BJU Int,2012,110(6 Pt B):E259-E266.
[33] Singh DV,Mete UK,Mandal AK,et al.A comparative randomized prospective study to evaluate efficacy and safety of combination of tamsulosin and tadalafil vs.tamsulosin or tadalafil alone in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.J Sex Med,2014,11(1):187-196.
[34] 孙元明,顾卫东,吕坚伟,等.联合应用坦索罗辛和托特罗定治疗男性顽固性下尿路症状的临床研究.中华男科学杂志,2010,16(9):790-793.