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

Overview
Specialty Endocrinology
Date 2019 May 22
PMID 31110491
Citations 11
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Abstract

The age-related decline of serum T occurs in ~20-30% of adult men and it is today defined as late-onset hypogonadism (LOH). In the elderly, such decline becomes more prevalent (up to 60%) and shows-up with erectile dysfunction (ED) and hypoactive sexual desire. A large body of experimental evidences have shown that the combination of T replacement therapy (TRT) and phosphodiesterase type 5 inhibitors (PDE5i) is, usually, effective in restoring erectile function in patients with LOH and ED who have not responded to monotherapy for sexual disturbances. In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Meta-analytic data have recognized to PDE5i a protective role on the cardiovascular health in patients with decreased left ventricular ejection fraction. In addition, several studies have shown pleiotropic beneficial effects of these drugs throughout the body (i.e., on bones, urogenital tract and cerebral, metabolic, and cardiovascular levels). TRT itself is able to decrease endothelial dysfunction, oxidative stress and inflammation, thus lowering the cardiovascular risk. Furthermore, untreated hypogonadism could be the cause of PDE5i ineffectiveness especially in the elderly. For these reasons, aging men complaining ED who have LOH should undergo TRT before or at the moment when PDE5i treatment is started.

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References
1.
Valenti S, Cuttica C, Fazzuoli L, Giordano G, Giusti M . Biphasic effect of nitric oxide on testosterone and cyclic GMP production by purified rat Leydig cells cultured in vitro. Int J Androl. 1999; 22(5):336-41. DOI: 10.1046/j.1365-2605.1999.00189.x. View

2.
Barrett-Connor E . Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women. Diabetes Care. 2000; 23(7):912-8. DOI: 10.2337/diacare.23.7.912. View

3.
Harman S, Metter E, Tobin J, Pearson J, Blackman M . Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001; 86(2):724-31. DOI: 10.1210/jcem.86.2.7219. View

4.
Lin C, Chow S, Lau A, Tu R, Lue T . Identification and regulation of human PDE5A gene promoter. Biochem Biophys Res Commun. 2001; 280(3):684-92. DOI: 10.1006/bbrc.2000.4220. View

5.
MORELAND R, Albadawi H, Bratton C, Patton G, Goldstein I, Traish A . O2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle. Am J Physiol Heart Circ Physiol. 2001; 281(2):H552-8. DOI: 10.1152/ajpheart.2001.281.2.H552. View