A review of combination therapy in patients with benign prostatic hyperplasia.
BACKGROUND
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.


OBJECTIVE
This article reviews key trials of monotherapy and combination alpha(1)ARV5ARI therapy in the treatment and prevention of BPH-related voiding dysfunction.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
McVary
Kevin T
KT
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611-3008, USA. k-mcvary@northwestern.edu
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000009:adverse effects / Q000627:therapeutic use*; D058668:Adrenergic alpha-1 Receptor Antagonists; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016055:Urinary Retention / Q000188:drug therapy
D058668:Adrenergic alpha-1 Receptor Antagonists; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase