PDE5 Inhibitors in the Treatment of LUTS

Abstract

Both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have a negative impact on patients' quality of life. The co-prescription of two active agents for these conditions will improve each condition and the addition of one drug to the other may potentiate the primary response of the first treatment and thereby improve the QoL of patients. Several epidemiological studies have indicated that the association between LUTS and ED is more than a co-incidence of age, with a possible cause and effect relationship. LUTS is more common in men with ED and there is a strong relationship between the severity of LUTS and the degree of erectile difficulty. Four pathophysiologies have been suggested to explain the relationship between LUTS and ED. There is a complex interaction between these mechanisms and there may be additional processes involved. These are: (1) alteration in nitric oxide levels; (2) autonomic hyperactivity; (3) changes in the Rho-kinase/endothelin pathway; and (4) pelvic vasculature atherosclerosis. Studies of all three easily available PDE-5 inhibitors have shown improvements in both LUTS and ED in men with significant problems in both areas without any substantial increase in side effect profile. Studies have also shown that the greatest improvements occurred with the combination of an alpha blocker and PDE-5 inhibitor when compared with either drug alone. Whilst significant improvements were seen in LUTS symptom scores, there was no significant improvement in flow rates with PDE-5 inhibitors when compared with placebo. High quality basic science studies of PDE-5 inhibitors on bladder muscle and alpha blocker agents on penile cavernosal tissue have provided several explanations for their modes of action. Even so, the mechanism of action of PDE-5 inhibitors in LUTS remains far from certain. More well-designed, placebo-controlled studies are needed to confirm the impact of these drugs, alone or in combination, on both ED and LUTS. However combination therapy appears appropriate for patients with both LUTS and ED. At present though, we should not routinely offer a combination of PDE-5 inhibitors and alpha blocker for the treatment of LUTS alone.