Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications

Conclusions Aging leads to a progressive decrease in androgen production that, in turn, leads to the development of LOH, defined by significant low T serum levels (in the lowest quartile) in the presence of signs and symptoms of hypogonadism (51). LOH could be due to both testicular and hypothalamic-pituitary dysfunction (32), and ED is one of its main symptoms. ED in LOH is linked to increased oxidative stress, subclinical inflammation, and subsequent endothelial dysfunction (101). In elderly men, it has been shown that LOH is also linked to lower cAMP pool and to an alteration of the cGMP signaling pathway. PDE5 gene lower expression is associated to aging and hypogonadism at the corpus cavernosum level. TRT is able to restore the expression of PDE5 gene and this effect is initially attributed to a direct regulation of the gene expression by T (38). Subsequently, this hypothesis was not confirmed, and the authors hypothesized that the lower expression of PDE5 in hypogonadism was due to the decreased smooth muscle cell content in corpora cavernosa. Therefore, T could able to increase PDE5 content by reversing these anatomical changes (39). Anyway, the increased PDE5 gene expression explains the reason for the possible failure of PDE5i administration in hypogonadal patients with ED. The timing of treatment with T and PDE5is in patients with hypogonadism and ED is a matter of debate (102). The initial approach to patients with ED encompasses the use of PDE5is (72) (Figure 2...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research