5-alpha reductase inhibitor improves lower urinary tract symptoms, regardless of gland size


Long-term treatment with finasteride resulted in consistent, clinically significant reductions in total prostate volume regardless of baseline volume.

Key Points

Whether patients received finasteride alone or in combination with the alpha-blocker doxazosin (Cardura), total prostate volume decreased significantly over 4 or more years of treatment, Steven A. Kaplan, MD, reported at the AUA annual meeting.

"The previous finding in MTOPS that combination treatment is the best overall therapy remains true," said Dr. Kaplan, professor of urology at Weill Cornell Medical College, New York. "However, these findings open up the possibility that we can look at a 5-alpha-reductase inhibitor [5-ARI] such as dutasteride [Avodart] and it might actually work in men with smaller prostates."

A previous analysis of MTOPS data showed that the combination of finasteride and doxazosin was effective across the range of prostate volumes from 25 to 40 grams (J Urol 2006; 175:217-20). These findings led MTOPS investigators to consider whether finasteride alone might also be effective in smaller prostates.

MTOPS involved 3,047 men with lower urinary tract symptoms randomized to placebo, doxazosin, finasteride, or the combination of doxazosin and finasteride. Total prostate volume was assessed by transrectal ultrasound in all randomized patients. The study had a mean follow-up of 4.5 years, and the primary endpoint was clinical progression of BPH.

Participants averaged 62.6 years of age, and they had a mean AUA symptom score of 16.9, mean peak urinary flow of 10.5 mL/second, mean postvoid residual volume of 68.1 mL, and mean PSA level of 2.4 ng/mL. Median total prostate volume was 31 cc.

The analysis revealed a 20% to 25% reduction in total prostate volume in men with a baseline prostate volume <25 cc, 25 cc to 30 cc, 30 cc to 40 cc, and >40 cc. The shrinkage with finasteride alone was equivalent to or better than that of combination therapy, suggesting the superior results with combination therapy versus doxazosin in MTOPS "was likely due to the significant finasteride-induced total prostate volume reduction that occurred in the combination therapy group."

"This is somewhat of a new and novel finding because we have always been under the impression that 5-alpha-reductase inhibitors seem to work better in larger prostates, but that doesn't necessarily mean they don't work in smaller prostates," Dr. Kaplan said.

"These data suggest that perhaps we should reconsider which patients with LUTS or BPH are 'right' for combination medical therapy."

Dr. Kaplan has been a consultant/adviser and investigator for Astellas Pharma, Pfizer, and Merck; he has been employed by Pfizer.

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