AUA: ED Drugs May Have Role in Treatment of BPH and LUTS

ANAHEIM, Calif., May 25 -- Treatments for erectile dysfunction may prove effective against benign prostatic hyperplasia and lower urinary tract symptoms, possibly because they share a common etiologic pathway.

Studies involving all three of the currently available type 5 phosphodiesterase (PDE5) inhibitors showed improvement in BPH and urinary symptoms, regardless of whether the patients had concomitant erectile dysfunction. The three studies, two from the U.S. and one from Germany, were reported at the American Urological Association meeting.

The data reinforce an emerging theoretical and scientific framework that posits a common pathway for development of erectile dysfunction, benign prostatic hyperplasia, and lower urinary tract symptoms, and, the research suggests, possibly overactive bladder, researchers said.

The larger of the two prospective, randomized trials was conducted by Kevin McVary, M.D., of Northwestern University, and colleagues. It involved 369 men who had erectile dysfunction and concomitant lower urinary tract symptoms.

The patients, whose mean age was 60, had about a six-year history of erectile dysfunction and a five-year history of BPH and lower urinary tract symptoms. They were randomized to placebo or to 50 mg of sildenafil (Viagra) taken nightly before bedtime or 1 hour before sexual activity.

Treatment continued for 12 weeks. The primary endpoints were change in the erectile function (EF) domain score of the International Index of Erectile Function, change in the International Prostate Symptom Score (IPSS), and change in maximum urinary flow (Q_max).

Overall, patients treated with sildenafil had a 6.32-point improvement in the IPSS compared to 1.93 for the placebo group (P<0.001). EF domain scores improved by an average of 9.17 in the sildenafil group and 1.86 in the placebo group (P<0.001). Q_max did not differ between groups at baseline or at the end of the study.

Stratification of the data by baseline severity showed that patients with severe (IPSS ?20) lower urinary tract symptoms improved substantially more compared with placebo than did those with moderate (IPSS 8-19) symptoms (P=0.0619). Among men with severe symptoms at baseline (54% of the cohort), substantially more had mild (16% vs. 4%) or moderate (57% vs. 36%) symptoms compared with placebo at the end of the study, the researchers found.

"The improvement in IPSS correlated with the IIEF changes," said Dr. McVary said. "Patients with more severe symptoms had more improvement, in a sense because they have more room for change."

He noted, however, that the researchers were surprised to find that the improvement did not correspond with the flow rate. "Although we didn't have an active comparator, the improvement looks to be comparable to what we might expect when giving alpha-blockers or a five-alpha reductase inhibitor," he said.

Asked to speculate about the lack of correlation between symptom improvement and flow rate, Dr. McVary said he and his colleagues initially suspected a predominance of urgency symptoms as opposed to obstruction. However, the data showed that both types of symptoms improved to a similar degree.

With respect to potential mechanisms involved in the co-existence of lower urinary tract symptoms and erectile dysfunction and the lack of flow improvement, Dr. McVary said that a pelvic deficiency in nitric oxide remains a viable explanation.

Other possibilities, he said, include an effect on bladder compliance, modulation of potential PDE5 effects on sensory innervation, and perhaps a change in pelvic flow affecting ischemia.

German investigators prospectively evaluated vardenafil (Levitra) as treatment for BPH in a randomized placebo-controlled study involving 222 men with moderate or severe symptoms.

The patients were randomized to placebo or vardenafil 10 mg BID for eight weeks, and the primary endpoints were change in IPSS, UROLIFE (a BPH quality-of-life questionnaire), and the EF domain of the IIEF.

The mean baseline IPSS was 16.8 in both groups. At the end of the study, vardenafil patients had a mean improvement of 5.9 compared with 3.6 for the placebo group (P=0.0013), reported Christian Stief, M.D., of Ludwig-Maximilians University in Munich.

Vardenafil also led to significantly greater improvement in the IPSS subscales for obstructive symptoms (3.2 vs. 1.9, P=0.0081) and irritative symptoms (2.6 vs. 1.7, P=0.0017).

The vardenafil group had significantly greater improvement on the UROLIFE questionnaire (P<0.0001 compared to placebo) and in the subscales for activity and perceived sexual life. IIEF scores improved by an average of 7.5 with vardenafil and 1.5 with placebo (P=0.0001).

The third study, a post hoc analysis of 156 men with erectile dysfunction and concomitant lower urinary tract symptoms showed that tadalafil (Cialis) significantly improved erectile function compared to placebo after 12 weeks of randomized therapy, reported Marc C. Gittelman, M.D., of South Florida Medical Research in Aventura, and colleagues.

Patients randomized to tadalafil started treatment at 5 mg/day for six weeks, followed by dose escalation to 20 mg/day over an additional six weeks.

Baseline IIEF scores averaged 13 to 14 in the placebo and tadalafil groups. The data were stratified by baseline urinary symptom severity.

Among patients with moderate symptoms, the erectile function score had improved by 6.8 points with tadalafil at six weeks versus 0.8 with placebo. At 12 weeks the tadalafil patients had a mean improvement of 8.3 compared with 1.7 in the placebo group.

In patients with severe symptoms, the EF domain score improved by 4.5 with tadalafil after six weeks compared to no change in the placebo group. At 12 weeks tadalafil patients had a mean improvement of 6.7 in the EF score compared with 0.7 in the placebo patients.

For all comparisons, tadalafil demonstrated a significant advantage over placebo (P<0.001). The magnitude of the tadalafil benefit did not differ between patients with moderate or severe lower urinary tract symptoms.

Multiple lines of evidence suggest a common pathophysiology for erectile dysfunction and BPH/lower urinary tract symptoms, said Dr. Kaplan. Such findings point toward the attractive possibility of treating the conditions with a single agent.