PDE-5 inhibitors show efficacy in new indications, including LUTS

April 7, 2007

The therapeutic revolution that began in 1997 when the first phosphodiesterase type-5 inhibitor was approved for erectile dysfunction is poised to expand. ED is just the first, most obvious use for PDE-5 inhibitors, said Culley Carson, MD, of the University of North Carolina, Chapel Hill.

The therapeutic revolution that began in 1997 when the first phosphodiesterase type-5 inhibitor was approved for erectile dysfunction is poised to expand. ED is just the first, most obvious use for PDE-5 inhibitors, said Culley Carson, MD, of the University of North Carolina, Chapel Hill.

"The day may be coming soon when every aging man takes an aspirin, a statin, and a PDE-5 inhibitor every day of his life," he told attendees at the Urology Congress Friday afternoon.

Most clinicians continue to use the three familiar agents, sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), to treat ED. But investigators and some clinicians are combining PDE-5 inhibitors with other ED therapies as well as with alpha-blockers to treat sexual dysfunction.

PDE-5 inhibitors are already used for pulmonary artery hypertension (PAH). Mounting evidence supports their use in hypertension, heart rate anomalies, and lower urinary tract symptoms.

More uses are expected. The 11 known PDE isoenzymes affect the central nervous system, adrenal cortex, testes, adipose tissue, liver, platelets, endocrine tissues, lung, kidney, retina, vascular smooth muscle, and other tissues, offering a variety of attractive therapeutic targets.

In ED treatment, there are growing reports of successful combinations of PDE-5 inhibitors with other treatment modalities. Patients who have failed PDE-5 inhibitors often respond well to a PDE-5 inhibitor plus testosterone therapy.

"It is important that all patients who fail PDE-5 inhibitors get a testosterone level," Dr. Carson said. "Response will clearly be enhanced with testosterone in patients with low levels."

Men who have failed both PDE-5 inhibitors and intraurethral alprostadil (MUSE) showed 100% response to combination therapy, Dr. Carson noted. PDE-5 inhibitor plus penile injection therapy produced more than 90% success in men who had previously failed both monotherapies.

Recent trials have confirmed anecdotal observations that PDE-5 inhibition reduced lower urinary tract symptoms. Patients reported reduction in irritation as well as increased voiding function.

Sildenafil is already used to increase oxygenation in PAH.

"It works with very good results in our pediatric and adult patients," Dr. Carson noted.

Evidence is also accumulating that PDE-5 inhibitors can moderate both diastolic and systolic blood pressure as well as heart rate.

"We may see PDE-5 inhibitors being used widely in the very near future," Dr. Carson said.