Logan Youlanda T, Belgeri Myra T
Department of Pharmacy Practice, Hampton University School of Pharmacy, Hampton, Virginia 23668, USA.
Am J Geriatr Pharmacother. 2005 Jun;3(2):103-14. doi: 10.1016/s1543-5946(05)00031-0.
Benign prostatic hyperplasia (BPH) is a medical condition occurring in older men (ie, those aged >60 years) resulting from enlargement of the prostate gland. Consequently, affected men may experience bother-some urinary tract symptoms and diminished quality of life. The risk of lower urinary tract symptoms and complications such as acute urinary retention (AUR) may increase if BPH is untreated. Currently, 2 classes of drugs-alpha-adrenergic blockers (alpha-blockers) and 5alpha-reductase inhibitors-are indicated for the treatment of BPH. Although the 2 classes are commonly used in combination, the evidence has frequently not been supportive of this practice. Results from the Medical Therapy of Prostatic Symptoms (MTOPS) trial, the largest and longest clinical trial on this topic to date, revisited the role of combination therapy in the treatment of BPH.
This review presents published trials evaluating alpha-blockers or 5alpha-reductase inhibitors used alone or in combination for the treatment of BPH.
A MEDLINE search was conducted (December 1974 to November 2004) using the MeSH term prostatic hyperplasia limited to the subheading of drug therapy. These results were cross-referenced with the MeSH term combination drug therapy. An additional search was conducted using the MeSH terms finasteride and adrenergic alpha-antagonists limited to adverse effects and therapeutic uses. These results were cross-referenced with prostatic hyperplasia and combination drug therapy. Review articles and meta-analyses were also used.
The Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group and the Prospective European Doxazosin and Combination Therapy studies were well-designed trials that failed to support the theory that combination therapy is preferred over alpha-blockers alone. Finasteride was also shown to be no better than placebo for the outcomes of symptom score and peak urinary flow rates. Other trials suggested that combination therapy (which included finasteride) was more effective at reducing symptom scores in men with enlarged prostates at 1 year and that alpha-blockers may be successfully discontinued once patients are stabilized on finasteride. Although it was a prespecified secondary end point, the incidence of surgery or AUR was reduced by 51% using finasteride over placebo. The additive benefit finasteride provides in reducing symptoms, risk of AUR, and invasive surgery was observed within the first year of treatment and correlated with larger prostate sizes (mean [SD], approximately 55 [26] mL). The MTOPS trial further demonstrated a relative risk reduction of 66% in clinical progression rates for the combination-therapy group versus 39% for the doxazosin group compared with placebo (P < 0.001); the doxazosin group was not statistically different from the finasteride monotherapy group. Improvements in symptom scores were greater in the combination-therapy group versus the doxazosin (P = 0.006) and finasteride monotherapy (P < 0.001) groups.
Based on the literature, combination therapy has been proven to relieve symptoms and delay progression of BPH in men with moderate to severe symptoms and moderately enlarged prostate glands.
良性前列腺增生（BPH）是一种发生于老年男性（即年龄>60岁者）的病症，由前列腺增大所致。因此，患病男性可能会出现令人烦恼的尿路症状，生活质量下降。若BPH未得到治疗，下尿路症状及诸如急性尿潴留（AUR）等并发症的风险可能会增加。目前，两类药物——α-肾上腺素能阻滞剂（α-阻滞剂）和5α-还原酶抑制剂——被用于治疗BPH。尽管这两类药物常联合使用，但证据往往并不支持这种做法。前列腺症状医学治疗（MTOPS）试验是迄今为止关于该主题规模最大、历时最长的临床试验，重新审视了联合治疗在BPH治疗中的作用。
本综述介绍已发表的评估单独使用或联合使用α-阻滞剂或5α-还原酶抑制剂治疗BPH的试验。
利用医学主题词（MeSH）“前列腺增生”进行MEDLINE检索（1974年12月至2004年11月），限定于药物治疗副标题。这些结果与MeSH词“联合药物治疗”交叉参照。另外利用MeSH词“非那雄胺”和“肾上腺素能α拮抗剂”进行检索，限定于不良反应和治疗用途。这些结果与“前列腺增生”和“联合药物治疗”交叉参照。还使用了综述文章和荟萃分析。
退伍军人事务部协作研究良性前列腺增生研究组以及前瞻性欧洲多沙唑嗪与联合治疗研究是设计良好的试验，但未能支持联合治疗优于单独使用α-阻滞剂这一理论。对于症状评分和最大尿流率结果，非那雄胺也未显示出比安慰剂更好的效果。其他试验表明，联合治疗（包括非那雄胺）在降低前列腺增大男性1年时的症状评分方面更有效，并且一旦患者在非那雄胺治疗下病情稳定，α-阻滞剂可能可以成功停用。尽管这是一个预先设定的次要终点，但与安慰剂相比，使用非那雄胺可使手术或AUR的发生率降低51%。在治疗的第一年就观察到非那雄胺在减轻症状、降低AUR风险和减少侵入性手术方面的附加益处，且与更大的前列腺体积（平均[标准差]，约55[26]mL）相关。MTOPS试验进一步证明，与安慰剂相比，联合治疗组的临床进展率相对风险降低66%，多沙唑嗪组为39%（P<0.001）；多沙唑嗪组与非那雄胺单药治疗组在统计学上无差异。联合治疗组的症状评分改善程度大于多沙唑嗪组（P = 0.006）和非那雄胺单药治疗组（P<0.001）。
基于文献，联合治疗已被证明可缓解中度至重度症状且前列腺中度增大男性的BPH症状并延缓其进展。
