Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management

Abstract

Benign prostatic hyperplasia (BPH) is a complex disease that is progressive in many men. BPH is commonly associated with bothersome lower urinary tract symptoms; progressive disease can also result in complications such as acute urinary retention (AUR) and BPH-related surgery. It is therefore important to identify men at increased risk of BPH progression to optimise therapy. Several factors are associated with progression, including age and prostate volume (PV). Serum prostate-specific antigen level is closely correlated with PV, making it useful for determining the risk of BPH progression. Medical therapy is the most frequently used treatment for BPH. 5-alpha-reductase inhibitors impact the underlying disease and decrease PV; this results in improved symptoms, urinary flow and quality of life, and a reduced risk of AUR and BPH-related surgery. Alpha-blockers achieve rapid symptom relief but do not reduce the overall risk of AUR or BPH-related surgery, presumably because they have no effect on PV. Combination therapy provides greater and more durable benefits than either monotherapy and is a recommended option in treatment guidelines. The Combination of Avodart and Tamsulosin (CombAT) study is currently evaluating the combination of dutasteride with tamsulosin over 4 years in a population of men at increased risk of BPH progression. A preplanned 2-year analysis has shown sustained symptom improvement with combination therapy, significantly greater than with either monotherapy. CombAT is also the first study to show benefit in improving BPH symptoms for combination therapy over the alpha-blocker, tamsulosin, from 9 months of treatment.

Figure 1

The role of 5-alpha-reductase (5αR) and dihydrotestosterone (DHT) in prostate growth

Figure 2

Effect of finasteride or placebo on symptom scores (on the Quasi-American Urological Association Symptom Scale) in the Proscar Long-term Efficacy and Safety Study. Reproduced from Ref. (18) with permission from the Massachusetts Medical Society. Values are mean (±SE) changes from baseline

Figure 3

Mean change in American Urological Association Symptom Index scores from baseline over 48 months. Reproduced from Ref. (49) with permission from Elsevier. *p < 0.001 between treatment groups; †p < 0.001 for differences for both treatment groups from month 24

Figure 4

Change in International Prostate Symptom Score following treatment with dutasteride, tamsulosin or dutasteride/tamsulosin in combination. Reproduced from Ref. (60) with permission from Elsevier. *p < 0.001 for combination vs. dutasteride; †p < 0.001 for combination vs. tamsulosin; ‡p = 0.18 for combination vs. tamsulosin; §p = 0.032 for combination vs. tamsulosin

Figure 5

Proposed algorithm for medical therapy of benign prostatic hyperplasia. Adapted from Ref. (64) with permission from Macmillan Publishers Ltd