Biochemical and genetic markers of erectile dysfunction

Erectile dysfunction (ED) is a very common pathology, affecting over 150 million men worldwide. The pathogenesis is typically multifactorial, involving a kaleidoscope of organic, endocrine, and psychogenic factors. In general, ED is divided into organic and psychogenic impotence, but most men with organic etiologies have an associated psychogenic component. Given the high frequency of this pathology, the identification of biochemical and genetic correlates and/or markers is of pivotal interest not only for treating preciously these patients and preventing serious psychological consequences but also for the high risk for occult cardiovascular disease (CVD) that often accompanies or follows this pathology. A variety of cardiovascular risk factors have been associated with both the onset and the severity of ED, including markers of endothelial function, thrombosis, and especially dyslipidemia, so that their measurement should now be considered as an important part of the increased global cardiometabolic risk profile in patients with ED. While nitric oxide (NO), asymmetric dimethylarginine (ADMA), and endothelin (ET) hold some promises as biochemical markers of both CVD and ED, there are several technical and clinical drawbacks that make their measurement overall meaningless in the clinical practice. As regards genetic polymorphisms, controversial results have been provided so far. Although some genetic markers were consistently associated with ED, other studies failed to demonstrate significant associations, highlighting a substantial bias in standardization of methodologies and patient enrolment. Nevertheless, further research in this area should be encouraged, since the first promising evidence that gene therapy might be effective to restore the decline in ED has been provided in the animal model.