Oral Agents: First-Line Therapy for Erectile Dysfunction

Oral agents are relatively non-invasive, reversible, readily administered and well tolerated; hence, they are emerging as first-line treatments for patients with erectile dysfunction. Two medications have been licensed in Europe: the dopamine agonist sublingual apomorphine, which influences central regulatory mechanisms, and the phosphodiesterase type 5 (PDE5) inhibitor sildenafil citrate, which affects local regulation of erectile function by potentiating the effects of nitric oxide. Two other potent, selective, reversible PDE5 inhibitors (tadalafil and vardenafil) are under regulatory review in Europe, the United States and other countries. In double-blind, placebo-controlled trials, these compounds significantly enhanced erectile function and increased the likelihood of successful sexual intercourse largely irrespective of etiology or severity of erectile insufficiency. Apomorphine and PDE5 inhibitors also significantly improved scores in the erectile function, orgasmic function, intercourse satisfaction and overall satisfaction domains of the International Index of Erectile Function. Oral agents were well tolerated; adverse events were generally mild or moderate, prompting premature treatment discontinuation in a small minority of patients. The chief adverse effects with apomorphine were nausea and headache, and with PDE5 inhibitors, headache, dyspepsia and flushing. Because of a potential pharmacodynamic interaction between PDE5 inhibitors and nitrates or nitric oxide donors that has been associated with hypotension, concomitant nitrate use is an absolute contraindication. However, the actual incidences of myocardial infarction in sildenafil and tadalafil patients are similar to those in placebo controls.