Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

Abstract

Objectives-Androgens are essential for the development and growth of the penis, and they regulate erectile physiology by multiple mechanisms. Our goal is to provide a concise overview of the basic research and how this knowledge can be translated into a new clinical paradigm for patient management. In addition, this new paradigm may serve as a basis for stimulating constructive debate regarding the use of testosterone in men, and to promote new, innovative basic and clinical research to further understand the underlying mechanisms of androgen action in restoring erectile physiology. Methods-A literature review was performed utilizing the US National Library of Medicine's PubMed database.Results-On the basis of evidence derived from laboratory animal studies and clinical data, we postulate that androgen insufficiency disrupts cellular-signaling pathways and produces pathologic alterations in penile tissues, leading to erectile dysfunction. In this review, we discuss androgendependent cellular, molecular, and physiologic mechanisms modulating erectile function in the animal model, and the implication of this knowledge in testosterone use in the clinical setting to treat erectile dysfunction. The new clinical paradigm incorporates many of the consensed points of view discussed in traditional consensed algorithms exclusively designed for men with androgen insufficiency. There are, however, novel and innovative differences with this new clinical paradigm. This paradigm represents a fresh effort to provide mandatory and optional management strategies for men with both androgen insufficiency and erectile dysfunction. Conclusions-The new clinical paradigm is evidence-based and represents one of the first attempts to address a logical management plan for men with concomitant hormonal and sexual health concerns.

Energy restriction ameliorates metabolic syndrome-induced cavernous tissue structural modifications in aged rats

“…These changes appear to parallel previous human observations that recently attracted more attention, not only concerning sexual performance, but in a wider context of male health. That is so because experimental research supports the point that testosterone deficiency profoundly affects angioarchitecture of cavernous tissue and impairs the erectile capacity (Tomada et al 2011;Traish et al 2007) and also because hypogonadism associates with MetS and is a risk factor for CVD (Jones 2007;Frederiksen et al 2012;Laughlin et al 2008;Vikan et al 2009). …”

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

“…Previous studies in animal models suggest that androgen deprivation reversibly alters the structure and function of the cavernous tissue (Traish and Kim 2005) and results in critical increase in the number of apoptotic trabecular SM cells, which compromise the veno-occlusive mechanism and erectile function (Shabsigh 1997;Traish et al 1999Traish et al , 2007. Nevertheless, the exact mode of androgen action in the regulation of erectile function in human remains unknown.…”

Androgens and male aging: current evidence of safety and efficacy

“…Testosterone is a determinant of glucose homeostasis and lipid metabolism [8] and plays also a significant role in the development and maintenance of bone and muscle mass. Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection [9]. The effects of phosphodiesterase type 5 (PDE5)-inhibitors are suboptimal in the presence of hypogonadal values of circulating testosterone [9].…”

“…Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection [9]. The effects of phosphodiesterase type 5 (PDE5)-inhibitors are suboptimal in the presence of hypogonadal values of circulating testosterone [9]. A relationship between lower urinary tact symptoms (LUTS) and circulating levels of testosterone has been difficult to prove but the association of LUTS with the metabolic syndrome and with ED is well established in the literature [10].…”