AUA 2009: Induction of Retrograde Ejaculation an Indication of Silodosin Efficacy in BPH

Martha Kerr

April 30, 2009

April 30, 2009 (Chicago, Illinois) — Results of 2 phase 3 studies reported here yesterday during the American Urological Association (AUA) 104th Annual Scientific Meeting show that silodosin (Rapaflo, Watson Pharmaceuticals, Inc) not only reduces urinary outlet obstruction in benign prostatic hyperplasia (BPH), but induces retrograde ejaculation, which should be considered a sign of efficacy rather than an adverse effect.

Silodosin was approved for BPH by the Food and Drug Administration in October 2008 and made available in the United States on April 12, 2009.

"Silodosin, a highly selective alpha-1A-adrenoceptor antagonist, promoted rapid and significant improvement of urinary symptoms associated with BPH in the 2 US clinical studies," lead investigator Leonard S. Marks, MD, director of the Urological Sciences Research Foundation in Culver City, California and professor of urology at the University of California at Los Angeles.

The studies randomly assigned 466 men to silodosin, 8 mg daily, and 457 men to placebo for 12 weeks. Subjects were aged 50 years and older with a baseline International Prostate Symptom Score (IPSS) of at least 13.

Men were examined and questioned at baseline and at weeks 1, 2, 4, and 12.

"The difference in symptom improvement between silodosin and placebo was already statistically significant at week 0.5, the earliest postbaseline measurement," Dr. Marks told meeting attendees.

Improvement in nocturia with silodosin compared with placebo was significant at week 1 of treatment; on a 5-point scale, a decrease of 0.5 points with silodosin compared with a drop of 0.3 points with placebo was seen (P = .0091).

Not only was there improvement in irritative and obstructive symptoms of BPH, with improvements sustained over the course of the 12 weeks of study, "these improvements were statistically significant after only 3 days to 1 week of treatment."

Symptom relief was accompanied by an increase in retrograde ejaculation, which could be viewed as an indication of efficacy rather than a true adverse event, according to investigator Claus G. Roehrborn, MD, professor and chair of urology at the University of Texas, Southwestern Medical Center in Dallas.

Using the same patient pool, Dr. Roehrborn and colleagues stratified patients according to whether they reported retrograde ejaculation as an adverse event during the study.

At 12 weeks, baseline International Prostate Symptom Score (IPSS) and peak urinary flow rate (Qmax) were comparable between groups. Of the 466 patients receiving active treatment, 335 had no retrograde ejaculation while 131 did. Improvements in IPSS and Qmax were significantly greater for patients without retrograde ejaculation.

Improvements in symptoms and peak flow rate were greater in the silodosin-treated patients with retrograde ejaculation than those receiving active treatment without it. "There was a trend toward significance for Qmax," Dr. Roehrborn reported.

"Silodosin appears to relax the smooth muscles of the lower urinary tract and the genital tract enough to induce retrograde ejaculation," he proposed. This is reflected in the finding that patients with the greatest relief in lower urinary tract symptoms had a higher likelihood of retrograde ejaculation.

"The observation suggests that retrograde ejaculation is actually an indirect indicator of the relaxation of the smooth musculature that silodosin induces," AUA spokesman Steve A. Kaplan, MD, professor of urology at Weil Cornell Medical College in New York told Medscape Urology.

"For the older BPH patient who experiences retrograde ejaculation, it may be a small tradeoff for the rapid and significant relief of urinary symptoms that treatment with silodosin offers," Dr. Kaplan commented.

AUA spokesman Kevin A. McVary, MD, professor of urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois, told Medscape Urology that "it is important to try to manage these patients."

"We need treatment options that work....This shows that the drug works," he said.

The studies were sponsored by Watson Pharmaceuticals. Dr. Marks and Dr. Kaplan have financial ties with the company. Dr. McVary has disclosed no relevant financial relationships.

American Urological Association (AUA) 104th Annual Scientific Meeting: Abstracts 1921 and 1922.Presented April 29, 2009.

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