Endothelial effects of drugs designed to treat erectile dysfunction.
Erectile dysfunction (ED) and endothelial dysfunction are common in individuals with multiple cardiovascular risk factors (CRFs) and are longitudinal predictors of cardiovascular events. ED is associated with systemic endothelial cell activation/dysfunction independent from CRFs or from diffuse, unrecognized vascular damage. The pathogenesis of endothelial dysfunction and ED is intimately linked through decreased expression and activation of endothelial nitric oxide (NO) synthase and the subsequent physiologic actions of NO. Furthermore, reduced biologic activity of endothelium-derived NO links atherosclerosis to ED and underscores the role of altered endothelium in the pathogenesis of both conditions. Evidence-based data suggest that daily use of phosphodiesterase type-5 inhibitors (PDE5-i) improves endothelial and erectile functions and that this benefit is lost upon drug withdrawal. Daily PDE5-i may also improve lower tract urinary symptoms related to benign prostatic hyperplasia through a reduction of adrenergic overtone. The relevance for these drugs in the prevention of complications in internal medicine diseases, i.e. cardiovascular disease, clotting disorders and autoimmune disease is uncertain. Finally, endothelial dysfunction is present in testosterone deficiency syndromes and replacement therapy is able to revert ED and to improve endothelial function. Aim of the present review is to discuss the systemic effects of drugs designed to treat ED, such as testosterone and PDE5-i, with regard to safety, unwanted effects and efficacy in improving endothelial function; finally, a goal-oriented approach to rehabilitation using daily vs. on-demand PDE5-i in difficult patients is discussed.
Aversa
Antonio
A
Internal Medicine Unit, Medical Pathophysiology Department, Sapienza University of Rome, Viale del Policlinico 155, Rome, Italy. antonio.aversa@uniroma1.it
Caprio
Massimiliano
M
Rosano
Giuseppe M C
GM
Spera
Giovanni
G
D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013739:Testosterone / Q000502:physiology
D010726:Phosphodiesterase Inhibitors; D013739:Testosterone; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5