Monotherapy versus combination drug therapy for the treatment of benign prostatic hyperplasia.

BACKGROUND: 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.

OBJECTIVE: This review presents published trials evaluating alpha-blockers or 5alpha-reductase inhibitors used alone or in combination for the treatment of BPH.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.