Injection therapy salvages 25% of PDE-5 failures

June 1, 2008

About one-quarter of men who fail to respond to phosphodiesterase type-5 (PDE-5) inhibitors for treatment of erectile dysfunction will respond to the drug on rechallenge if they are first exposed to a short-term course of intracavernosal injection (ICI) therapy.

Key Points

Sixty-eight of the 76 patients (89%) who failed an initial course of sildenafil citrate (Viagra) were able to achieve penetration with ICI. Of those 68, 18 were later able to have intercourse, using sildenafil alone, a salvage rate of 24%.

"Even though you may be committing a patient who failed a pill to injections, it's not unreasonable to challenge the patient with pills 6 months after injections begin, providing the patient has a good response to [ICI]," said John P. Mulhall, MD, director of sexual medicine programs and associate professor of urology at Weill-Cornell Medical College, Cornell University.

Mean patient age in the study was 52±31 years, with a mean duration of erectile dysfunction of 2.6±1.2 years. One-third of the men had hypertension. Other conditions in the comorbidity profile included body mass index >25 (35%), cigarette smoking history (current or past, 25%), radical prostatectomy (22%), hyperlipidemia (18%), diabetes (14%), and coronary artery disease (12%).

All patients had failed a course of sildenafil, defined as failure to achieve penetration with 100 mg of the drug taken preprandially on at least four occasions. Subjects completed International Index of Erectile Function (IIEF) questionnaires and a global efficacy question prior to trying sildenafil, while on sildenafil, and while on ICI.

Mean pre- and post-sildenafil erectile function domain scores were 17±6 and 22±4, respectively. That score rose to 28±3.5 during ICI therapy.

Most notable, however, was the fact that the men who responded to sildenafil on rechallenge, after at least 3 months on ICI, saw their mean erectile function score increase from 21±3 to 27±2.

"There hasn't been evidence of this published previously, but our experience was that we would put people on injections and a portion would come back and say, 'I've tried the pills again and they're working,'" Dr. Mulhall said at the European Association of Urology annual congress.

"We were actually surprised that 24% of these patients who met rigorous criteria for failure had become responders."

Success still unexplained

Explaining the post-ICI rechallenge phenomenon is difficult, Dr. Mulhall said. It could come down to psychological reasons, physiologic factors, or a combination of the two.

"Does it work because we're restoring confidence and taking care of some secondary psychological component?" he asked. "Men who go significant periods of time without good erections have an erosion of confidence. Maybe once that stress or adrenaline level drops, they're more likely to respond to pills.

"It's also possible that we're doing something for these patients' vasculature. Maybe we're 'repriming the pump,' or the endothelial function of the penis. We can't say for sure."

Dr. Mulhall noted a controversial 2007 paper from the University Medical Center Hamburg-Eppendorf in Germany that suggested that 1 year of sildenafil treatment may improve blood flow in the penis (Asian J Androl 2007; 9:134-41).

The idea that ICI and sildenafil rechallenge may have positive physiologic effects is supported by the fact that the most reliable predictors of failure in the study were diabetes, cigarette smoking, BMI >30, and radical prostatectomy.

"Those four groups have the greatest organic components, so it may be that even if a psychological component exists, we still may not be able to overcome it in men who exhibit these factors," Dr. Mulhall suggested.

Dr. Mulhall is a consultant/adviser and lecturer for Pfizer and Eli Lilly.