Testosterone and Erectile Dysfunction Short title – Testosterone and Erectile Dysfunction

Introduction Aging is associated with a decline in several important health factors in men, such as decreased muscle mass, muscle strength, physical performance, bone mineral density, blood and many age-related clinical features are closely associated with androgen deficiency, including erectile function. Not surprisingly, many men are reluctant to discuss erectile dysfunction with their physicians, and thus the condition remains under-diagnosed. Nevertheless, albeit a likely underestimation of the condition, experts have estimated that approximately 30 million men in the United States and 0.5 million men in the UK between the ages of 40-70 years suffer from varying forms of erectile dysfunction (ED) (Agarwal et al, 2006). The introduction of phosphodiasterase-5 (PDE-5) inhibitors for the treatment of ED made a significant impact both in terms of clinical efficacy, and increasing the awareness of the condition. Some men however, fail to respond to PDE-5 inhibitors alone. Interventional studies have demonstrated that testosterone replacement therapy, in men with sub-physiological concentrations of testosterone, improves erectile function in men who have potential of PDE5 inhibitors will only become manifest in a eugonadal state (Gooren, 2006). Indeed, recent studies have demonstrated a close relationship between testosterone and ED (Yassin and Saad, 2006a, 2007) and suggest that testosterone therapy may be a valuable option for an increasing number of affected men. Furthermore, European guidelines suggest that all men presenting with ED should have their testosterone levels measured (Wespes et al., 2006). Erectile dysfunction (ED) is defined as the inability to achieve or maintain erections sufficient for satisfactory sexual intercourse (NIH Consensus Conference, 1993). Formerly dismissed as a psychological condition, ED is now known as a treatable disorder and an important risk-marker for cardiovascular disease (Montorsi et al, 2004, Yassin and Saad JU 2007b). The physiological mechanism of normal penile erection is dependent on trapping incoming blood within the cavernosal bodies to increase pressure and volume. This physiological process, namely the veno-occlusive mechanism, depends upon the integrity of endocrine, hormonal, neurological and vascular components, as well as the fibroelastic properties of the cavernosal tissue. The penile corpus cavernosum is a vascular bed, and any alterations to its structure can produce vascular dysfunction (Krane et al, 1989). Cavernosal tissues from men with erectile dysfunction have been demonstrated to exhibit reduced lacunar spaces, reduced smooth muscle content, and a concomitant increase in connective tissue deposition (Mersdorf et al, 1991; Karadeniz et al, 1996). Indeed, changes in penile tissue structural integrity is …