Combo therapy packs double punch against LUTS, ED

July 1, 2006

Atlanta-Combining an alpha-blocker with a phosphodiesterase-5 (PDE-5) inhibitor appears to produce a greater therapeutic benefit in men with lower urinary tract symptoms than either drug alone, according to a study from Weill Cornell Medical College, New York.

After 12 weeks of treatment, International Prostate Symptom Scores (IPSS) dropped nearly five points, from 17.3 to 13.5, in men receiving combination therapy compared with a 3.2-point drop with the alpha-blocker alone and a 2.0-point drop with the PDE-5 inhibitor alone. In addition, scores on the International Index of Erectile Function (IIEF) improved 9.5 points in the combination therapy group compared with 2.9 points in the alpha-blocker group and 7.1 points in the PDE-5 inhibitor group.

The results are encouraging, but require confirmation, lead author Steven A. Kaplan, MD, professor of urology at Weill Cornell, told Urology Times. Dr. Kaplan presented the results of the study at the 2006 AUA annual meeting here.

Synergistic agents

The study involved 62 men, 50 to 76 years of age, with diagnosed but as yet untreated LUTS and erectile dysfunction. The men were randomized to receive alfuzosin hydrochloride (Uroxatral), 10 mg daily; to sildenafil citrate (Viagra), 25 mg daily; or to a combination of alfuzosin, 10 mg, and sildenafil, 25 mg daily. Eighty-two percent of the men completed the trial.

"We found, not surprisingly, that the alpha-blocker helped urination and that sildenafil also helped urination, but the best effects were achieved by combining the two," Dr. Kaplan said. "In other words, sildenafil helped the alpha-blocker's effect on voiding function and the alpha-blocker enhanced sildenafil's efficacy in erectile dysfunction."

Dr. Kaplan said the reason the combination produces what appear to be synergistic effects is unknown, but most theories rest upon the possible common mechanisms of both types of drugs.

"We know that alpha receptors are anti-erectogenic. There is speculation that if you block the blocker, the effects of the PDE-5 inhibitor are enhanced. We have used alpha-blockers as a therapy for erectile dysfunction as part of the so-called tri-mix injection therapy (papaverine, phentolamine, prostaglandin E1) and, in fact, we did a study in 1998 showing that the addition of oral alpha-blockers to intracavernosal injection therapy enhanced the effects of the therapy," he said.

Dr. Kaplan explained that prostatic smooth muscle cells display PDE-5, as well as PDE-4 and PDE-11 receptors, and that blocking those receptors may cause the muscle to relax, thereby improving symptoms.