Pharmacology and perspectives in erectile dysfunction in man

Penile erection is a perfect example of microcirculation modulated by psychological factors and hormonal status. It is the result of a complex neurovascular process that involves the integrative synchronized action of vascular endothelium; smooth muscle; and psychological, neuronal, and hormonal systems. Therefore, the fine coordination of these events is essential to maintain penile flaccidity or allow erection; an alteration of these events leads to erectile dysfunction (ED). ED is defined as the consistent or recurrent inability of a man to attain and/or maintain a penile erection sufficient for sexual activity. A great boost to this research field was given by commercialization of phosphodiesterase-5 (PDE5) inhibitors. Indeed, following the discovery of sildenafil, research on the mechanisms underlying penile erection has had an enormous boost, and many preclinical and clinical papers have been published in the last 10 years. This review is structured to provide an overview of the mediators and peripheral mechanism(s) involved in penile function in men, the drugs used in therapy, and the future prospective in the management of ED. Indeed, 30% of patients affected by ED are classified as “nonresponders,” and there is still an unmet need for therapeutic alternatives. A flowchart suggesting the guidelines for ED evaluation and the ED pharmacological treatment is also provided.