Phosphodiesterase-5 Inhibitors Don't Help Everyone With Erectile Dysfunction

By Will Boggs MD

March 31, 2020

NEW YORK (Reuters Health) - Phosphodiesterase 5 (PDE5) inhibitors do not appear to benefit certain subgroups of men with erectile dysfunction (ED), according to a systematic review and meta-analysis.

"It is important to acknowledge the main factors underlying ED in a particular individual," Alexander Stridh of Karolinska Institute, in Solna, Sweden, told Reuters Health by email. "Some patients might benefit more from a nonpharmacological intervention, e.g., psychotherapy, and some patients might benefit more from a medication."

ED can result from numerous physical causes, but it can also be of psychogenic origin. Numerous trials have demonstrated the benefits of PDE5 inhibitors in men with ED, but there has been little analysis of placebo effects.

Stridh and colleagues evaluated the change in erectile function, as measured by the erectile function domain of the International Index of Erectile Function (IIEF-EF) questionnaire, among patients in the placebo arm of randomized clinical trials of PDE5 inhibitors.

Their analysis included 63 studies with a total of more than 12,000 men with ED. The mean study duration was 14 weeks (range, 4-104 weeks).

The overall effect size in the treatment arm of the 59 studies that did not follow prostate-cancer treatment was large (Hedges g, 1.25), whereas the effect size in the placebo arm showed a small to moderate improvement of erectile function (Hedges g, 0.35), with a large difference in favor of active drug (Hedges g, 1.04), the researchers report in JAMA Network Open.

In patients with posttraumatic stress disorder (PTSD), there were large responses in both the treatment arm (Hedges g, 1.12) and the placebo arm (Hedges g, 0.77), with only a moderate effect size in favor of the PDE5 inhibitor (Hedges g, 0.40).

"The results seen for the PTSD-related ED trials might indicate that ED caused by mainly psychogenic factors might be subjected to a larger influence by the placebo effect," Stridh said. "It would be interesting to see what the effect size would be in the placebo arm in a clinical trial with younger patients who would have mainly performance-anxiety-related reasons for ED."

In contrast, there was no significant difference in effect size between PDE5 inhibitors and placebo in the recovery of erectile function after prostate surgery or radiotherapy.]

"PDE5 inhibitors are very effective in many patients, but they also have side effects, which in rare cases can be serious, and it is important to consider what would be the best treatment option for each individual patient," Stridh said. "I suspect that particularly younger patients without significant comorbidities could benefit well from nonpharmacological treatment options."

"I would also like to see that the practice with daily PDE5 inhibitors for recovery of nerve function after surgery or radiotherapy is put into more question, since it does not seem to be backed by strong evidence," he said.

Stridh added, "I would like to emphasize that Viagra and other PDE5 inhibitors showed a much larger effect than placebo in many of the trials included in our analysis and that these drugs are very effective in many patients beyond a potential placebo component."

The study did not have commercial funding, and none of the researchers reports conflicts of interest.

SOURCE: JAMA Network Open, online March 20, 2020.