McVary Kevin T
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-3008, USA.
Clin Ther. 2007 Mar;29(3):387-98. doi: 10.1016/s0149-2918(07)80077-4.
Trials of monotherapy with alpha(1)-adrenergic-receptor antagonists (alpha(1)ARAs) and 5 alpha-reductase inhibitors (5ARIs) have found that the former drug class is effective in managing benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and improving the maximal urinary flow rate in shortand long-term treatment, regardless of prostate size, whereas the latter drug class is effective in reducing prostate size and preventing disease progression in longer-term treatment. The differing mechanisms of action and areas of efficacy of these 2 drug classes make them promising candidates for combination therapy.
This article reviews key trials of monotherapy and combination alpha(1)ARV5ARI therapy in the treatment and prevention of BPH-related voiding dysfunction.
MEDLINE (1976-2006) and the Cochrane Central Register of Controlled Trials (1976-2006) were searched for relevant clinical trials and reviews using the terms benign prostatic byperplasia, lower urinary tract symptoms, LUTS, alpha-adrenergic-receptor antagonists, alpha-blockers, 5 alpha-reductase inhibitors, combination therapy, MTOPS, SMART, PREDICT, adverse events, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, and finasteride. Abstracts from selected professional conferences also were reviewed.
Three previous trials of alpha(1)ARA/5ARI therapy found no therapeutic benefit for combination therapy relative to monotherapy, but their conclusions were limited to some extent by their designs, particularly the duration of treatment. Data from the Medical Therapy of Prostatic Symptoms (MTOPS) study, however, indicated a potential role for long-term use of alpha(1)ARA/5ARI therapy, particularly in patients with greater symptom severity (mean score of 17 on the American Urological Association symptom index), larger prostate volume (mean, 32 g), and higher prostate-specific antigen (PSA) levels (>1.5 ng/mL) at baseline. In the MTOPS study, combination therapy with the alpha(1)ARA doxazosin and the SARI finasteride was significantly more effective than either component alone in reducing BPH-related symptoms (P=0.006 vs doxazosin monotherapy; P<0.001 vs finasteride monotherapy) and lowering the rate of overall clinical progression (P<0.001 vs either monotherapy). In addition, there are data from a subgroup analysis of MTOPS suggesting that the presence of prostatic inflammation may indicate a greater likelihood of treatment efficacy with combination alpha(1)ARA/5ARI therapy.
The available data suggest that combination alpha(1)ARA/5ARI therapy is beneficial in the treatment of BPH and the associated symptoms. The greatest efficacy was evident in patients with an enlarged prostate, more severe symptoms, and higher PSA levels. There are limited data suggesting that the presence of prostatic inflammation may indicate a greater likelihood of treatment efficacy with combination therapy.
α1肾上腺素能受体拮抗剂（α1ARAs）和5α还原酶抑制剂（5ARIs）的单药治疗试验发现，前一类药物在短期和长期治疗中均能有效管理良性前列腺增生（BPH）相关的下尿路症状（LUTS）并提高最大尿流率，无论前列腺大小如何；而后一类药物在长期治疗中能有效缩小前列腺体积并预防疾病进展。这两类药物不同的作用机制和疗效领域使其成为联合治疗的有前景的候选药物。
本文综述了α1ARV5ARI单药治疗和联合治疗在治疗和预防BPH相关排尿功能障碍方面的关键试验。
在MEDLINE（1976 - 2006年）和Cochrane对照试验中央注册库（1976 - 2006年）中检索相关临床试验和综述，使用的检索词有良性前列腺增生、下尿路症状、LUTS、α肾上腺素能受体拮抗剂、α阻滞剂、5α还原酶抑制剂、联合治疗、MTOPS、SMART、PREDICT、不良事件、阿夫唑嗪、多沙唑嗪、坦索罗辛、特拉唑嗪、度他雄胺和非那雄胺。还查阅了选定专业会议的摘要。
先前三项α1ARA/5ARI治疗试验发现联合治疗相对于单药治疗无治疗益处，但其结论在一定程度上受到设计限制，尤其是治疗持续时间。然而，前列腺症状医学治疗（MTOPS）研究的数据表明，长期使用α1ARA/5ARI治疗有潜在作用，特别是对于基线时症状更严重（美国泌尿外科学会症状指数平均评分为17分）、前列腺体积更大（平均32克）和前列腺特异性抗原（PSA）水平更高（>1.5 ng/mL）的患者。在MTOPS研究中，α1ARA多沙唑嗪和5ARI非那雄胺联合治疗在减轻BPH相关症状方面比单独使用任何一种成分都显著更有效（与多沙唑嗪单药治疗相比，P = 0.006；与非那雄胺单药治疗相比，P < 0.001），并降低总体临床进展率（与任何一种单药治疗相比，P < 0.001）。此外，MTOPS的亚组分析数据表明，前列腺炎症的存在可能表明α1ARA/5ARI联合治疗更有可能产生治疗效果。
现有数据表明，α(1)ARA/5ARI联合治疗对BPH及其相关症状的治疗有益。在前列腺肿大、症状更严重和PSA水平更高的患者中疗效最为明显。有限的数据表明，前列腺炎症的存在可能表明联合治疗更有可能产生治疗效果。
