Erectile Dysfunction Ageing and Erectile Dysfunction Carla Costa,1 Ronald Virag2 and Pedro Vendeira3


1. Invited Professor, Department of Biochemistry and Laboratory for Molecular Cell Biology, Faculty of Medicine, University of Porto; 2. Medical Director, Centre d’Explorations et Traitements de l’Impuissance (CETI), Paris; 3. Urologist, Department of Urology, S João Central Hospital, Porto, and Invited Professor of Molecular Cell Biology and Urology, Faculty of Medicine, University of Porto


Abstract


As average life expectancy is rising, a corresponding increase in the number of men reporting erectile dysfunction (ED) should be expected. Vasculogenic ED is recognised as the most prevalent aetiology in the ageing male and is closely associated with the development of endothelial dysfunction (EDys) and atherosclerosis. In fact, in advancing age ED may often constitute the first manifestation of systemic vasculopathy and is considered to be a harbinger and possible marker of clinically undiagnosed vascular disorder. The concomitant presence of vascular risk factors (VRFs), the decline in androgens and a disruption of vascular repair mechanisms are thought to further aggravate endothelium and erectile malfunction. Therefore, prevention measures with changes in lifestyle to control VRFs in the elderly are a mainstay in ED management, being accountable for an increased responsiveness to available ED therapies. In this article we review currently available data on ageing ED pathophysiology, EDys, alterations in vascular repair processes and the management, prevention and therapy of ED in the elderly.


Keywords


Ageing, erectile dysfunction (ED), vascular risk factors (VFRs), endothelial dysfunction (EDys), testosterone, angiogenesis, vasculogenesis, phopshodiesterase type-5 inhibitors, intracavernous injections


Disclosure: The authors have no conflicts of interest to declare. Received: 26 May 2010 Accepted: 5 July 2010 Citation: European Urological Review, 2010;5(1):44–50 Correspondence: Carla Costa, Laboratory for Molecular Cell Biology, Faculty of Medicine of the University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal. E: carcosta@med.up.pt


Pathophysiology of Erectile Dysfunction in the Elderly Man Erectile Tissue


Erectile tissue is composed of cavernous sinusoidal spaces lined with vascular endothelial cells (ECs) separated by the trabecula with bundles of smooth-muscle cells (SMCs), several autonomic nerves and an extracellular matrix (ECM) formed by collagen, elastic fibres and fibroblasts.1,2


of arterial blood.5,6


This initial inflow of blood increases shear stress and stimulates the production of endothelial NO (eNO) and the release of prostanoids and endothelium-derived hyperpolarising factors (EDHFs).9


Penile erection is a neurovascular phenomenon under psychological control that requires intact neural innervation, viable SM tissue and functional ECs. All of these cellular components play essential roles in physiological erections. They control the production/release of neurotransmitters that initiate the erectile process, and of vasorelaxation mediators that further regulate SMC relaxation and EC vasodilation, crucial for the maintenance of an erection.3


The interaction between these corporeal compartments is essential for the erectile process and any cellular and/or molecular impairment may result in erectile dysfunction (ED).


Physiological Erection – What Changes with Ageing? During sexual arousal an initial stimulus starting from supraspinal centres travels through the spinal cord, reaches the corpora cavernosa (CC) and, ultimately, travels along the cavernosal nerves. Terminal branches of the cavernosal nerves release neural nitric oxide (nNO), initiating the erectile process.4


nNO is diffused into the


adjacent corporeal SM, activating multiple intracellular signalling cascades that promote SMC relaxation and an nNO-mediated inflow


44


These events result in the arterial engorgement of sinusoidal spaces and an increase in intracavernous pressure with the subsequent compression of the subalbugineal venous plexus, activating the veno-occlusive mechanism.3


With ageing, all of these


erectile components and molecular and haemodynamic events may be affected, resulting in the impairment of erectogenesis and ED.


In the aged man, alterations of erectile function have been associated with neurogenic failure and arteriogenic/venous malfunction compromising the initiation and/or maintenance of an erection.10 Although recognising the relevance of all of these cellular interactions, vasculogenic ED was recognised as the most common aetiology in the elderly, promoted by occlusive disease of the pudendal–cavernosal–helicine arterial tree through the development of atherosclerosis.11,12


In fact, the geriatric man commonly presents


several vascular risk factors (VRFs) that predispose him to the development of atherosclerotic lesions as a consequence of endothelial dysfunction (EDys). This condition refers to the disruption of endothelium functional integrity, in which the ability of ECs to respond to vasodilation/vasoconstriction stimuli is impaired.13


In © TOUCH BRIEFINGS 2010


Effective SMC relaxation may also be achieved through the action of vasoactive intestinal peptide (VIP), acetylcholine, calcitonin-related peptide and prostaglandin E1 (PGE1).6–8


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