This Article Full Text (PDF) All Versions of this Article: 1756287209344992v1 1/4/179    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Aversa, A. Articles by Lenzi, A. Social Bookmarking                         What's this?

Testosterone and phosphodiesterase type-5 inhibitors: new strategy for preventing endothelial damage in internal and sexual medicine?

Dip.to Fisiopatologia Medica, Room 37, Viale Policlinico 155, 00161 Rome, Italy, antonio.aversa{at}uniroma1.it

Roberto Bruzziches

Department of Medical Pathophysiology, Sapienza University of Rome, Rome, Italy

Davide Francomano

Department of Medical Pathophysiology, Sapienza University of Rome, Rome, Italy

Marco Natali

Department of Medical Pathophysiology, Sapienza University of Rome, Rome, Italy

Andrea Lenzi

Department of Medical Pathophysiology, Sapienza University of Rome, Rome, Italy

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone (e.g. nitric oxide; NO), cell adhesion (e.g. endothelins, interleukins), and the homeostasis of clotting and fibrinolysis (e.g. plasminogen inhibitors, von Willebrand factor). The degeneration of endothelial integrity promotes adverse events (AEs) leading to increased atherogenesis and to the development of vascular systemic and penile end-organ disease. Testosterone (T) is an important player in the regulation of vascular tone through non-genomic actions exerted via blockade of extracellular-calcium entry or activation of potassium channels; also, adequate T concentrations are paramount for the regulation of phosphodiesterase type-5 (PDE5) expression and finally, for the actions exerted by hydrogen sulphide, a gas involved in the alternative pathway controlling vasodilator responses in penile tissue. It is known that an age-related decline of serum T is reported in approximately 20 to 30% of men whereas T deficiency is reported in up to 50% of men with metabolic syndrome or diabetes. A number of laboratory and human studies have shown the combination of T and other treatments for erectile dysfunction (ED), such as PDE5 inhibitors, to be more beneficial in patients with ED and hypogonadism, who fail monotherapy for sexual disturbances.

The aim of this review is to show evidence on the role of T and PDE5 inhibitors, alone or in combination, as potential boosters of endothelial function in internal medicine diseases associated with reduced T or NO bioavailability, i.e. metabolic syndrome, obesity, diabetes, coronary artery disease, hyperhomocysteinemia, that share common risk factors with ED. Furthermore, the possibility of such a strategy to prevent endothelial dysfunction in men at increased cardiovascular risk is discussed.

Key Words: endothelial dysfunction • erectile dysfunction • phosphodiesterase type-5 inhibitors • testosterone • cardiovascular disease • hydrogen sulphide • adenosine diphosphate

This version was published on October 1, 2009

Therapeutic Advances in Urology, Vol. 1, No. 4, 179-197 (2009)
DOI: 10.1177/1756287209344992


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?