Pathophysiology of erectile dysfunction: the contributions of trabecular structure to function and the role of functional antagonism

Erectile dysfunction (ED) is estimated to impact more than 150 million men this year worldwide, An understanding of the pathophysiology of ED both fur thers the basic scientific knowledge of disease processes and provides a ra tional design of pharmacotherapy, At present, there are two major views reg arding the pathophysiology of ED. In the first hypothesis, the oxygen tensi on-dependent changes in the penis during erection are proposed to impact co rpus cavernosum structure by inducing various cytokines, vasoactive factors and growth factors at the two different oxygen tensions (flaccidity and er ection) which, in turn, alter smooth muscle metabolism and connective tissu e synthesis. Decreases in the corpus cavernosum smooth muscle/connective ti ssue ratio have been correlated with an increased likelihood of diffuse Ven ous leak and a failure of the veno-occlusive mechanism in prospective patie nt studies. Evidence for such a hypothesis incorporates nocturnal penile tu mescence and circadian changes in oxygenation as important in maintaining e rectile health. The alternate hypothesis proposes that ED is the result of a metabolic imbalance between relaxatory and contractile processes within t he trabecular smooth muscle such that contractile processes predominate. Ba sed on this hypothesis, therapy can be accomplished via drugs which shift t his balance towards vasodilatation, or by gene therapy approaches to supple ment the deficient components favoring smooth muscle relaxation. Both of th ese hypotheses predict a management strategy for ED that impacts pharmacoth erapeutics. In this review of the pathophysiology of ED, each hypothesis wi ll be examined and a synthesis devised incorporating both views. The future of research in this area as well as pharmacotherapy in ED in terms of path ophysiology is discussed including the merits and drawbacks of prophylaxis and prevention of ED.