The Role of Steroids in Endothelial Function in the Aging Male

Antonio Aversa, Roberto Bruzziches,, Davide Francomano, Emanuela A Greco, Silvia Migliaccio, Andrea Lenzi
US Endocrinology, 2011;7(2):145-9

Abstract

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone, cell adhesion, and the homoeostasis of clotting and fibrinolysis. The degeneration of endothelial integrity promotes adverse events leading to atherogenesis. Circulating levels of endogenous hormones decline during aging and this may contribute to the occurrence of major adverse cardiovascular events, independently of gender differences. During the last decade, more attention has been drawn to the importance of testosterone, estradiol and adrenal androgens in the pathophysiology, prevention, and treatment of male aging-associated diseases. A considerable body of literature is available indicating that steroid hormones, particularly the sex steroids, are known to modulate endothelial function in all vascular beds and that their deficiency may promote endothelial dysfunction. Testosterone decrease and increased mineralocorticoid activity in the aging male are frequent and may yield endothelial dysfunction and increased cardiovascular burden. We recommend careful hormonal investigations in men who present comorbidities such as diabetes, hypertension and dyslipidemia.
Keywords: Endothelial function, cardiovascular disease, hormones, atherosclerosis, aging
Disclosure: Antonio Aversa, MD, PhD, has received grants from Bayer Schering Pharma and Eli Lilly. Silvia Migliaccio, MD, PhD, is a consultant for Eli Lilly. The remaining authors have no conflicts of interest to declare.
Received: July 08, 2011 Accepted July 29, 2011 Citation US Endocrinology, 2011;7(2):145-9
Correspondence: Antonio Aversa, MD, PhD, Department of Medical Pathophysiology, ‘La Sapienza’ University of Rome, Viale Policlinico 155, 00161 Rome, Italy. E: antonio.aversa@uniroma1.it
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The impairment of vascular endothelium is an early event in the development of diseases that may later become clinically overt, such as local and systemic atherosclerosis, myocardial infarction, cerebral ischaemia and erectile dysfunction. Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone, cell adhesion and the homoeostasis of clotting and fibrinolysis. The degeneration of endothelial integrity promotes adverse events leading to atherogenesis, such as infiltration of the vessel wall by macrophages loaded with oxidised lipoproteins.1 The pathogenesis of endothelial dysfunction is intimately linked through increased expression and activation of endothelial nitric oxide (NO) synthase and the subsequent physiological actions of NO. Reduced biological activity of endothelium-derived NO links human atherosclerosis to cardiovascular disease (CVD) and underscores the role of altered endothelium in the pathogenesis of both conditions. Coronary artery disease (CAD) represents one of the most common and costly atherogenic diseases in the Western world. It is more common in men aged 30–50 years, compared with women of similar age, an observation that has often suggested harmful effects of steroids on the coronary circulation.2 Although endogenous hormones have an impact on CVD, their role has remained largely unknown for many years. During the last decade more attention has been drawn to the importance of testosterone, oestrogens and adrenal androgens in the pathophysiology, prevention and treatment of male CVD. A considerable body of literature is available indicating that steroid hormones, particularly the sex steroids, are able to modulate endothelial function in all vascular beds and their deficiency promotes endothelial dysfunction. These observations point to the clinical relevance of the role of steroids in vascular health, and to the treatment of patients with hormonal deficiencies and increased cardiovascular risk factors with appropriate hormone formulations with the aim of attaining physiological circulating levels. The aim of this article is to give an overview of the role of sex steroid hormones in the control of vascular tone and provide evidence that these mechanisms are involved in the atherogenic process in the ageing male.

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