A Rationale for the Use of Testosterone “Salvage” in Treatment of Men With Erectile Dysfunction Failing Phosphodiesterase Inhibitors

Abstract

An age-related decline of serum testosterone (T) is reported in approximately 20% to 30% of men. However, the evaluation of total T levels may be misleading because of an increase in sex hormone-binding globulin (SHBG). Free and bioavailable T levels seem to be a better biochemical marker. Observational studies show that T concentrations are consistently lower among men with cardiovascular disease but not with erectile dysfunction (ED), suggesting a possible preventive role that requires critical evaluation with prospective studies. Hormonal replacement therapy can induce both beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of high-density lipoprotein (HDL) cholesterol, plasminogen activator inhibitor type-1, lipoprotein (a), fibrinogen, and visceral fat mass in hypogonadal men. By contrast, the possible beneficial effects of T in cardiovascular disease include antiatherogenic and coronary vasodilator effects. Shortterm interventional studies show that T produces a modest but consistent improvement in cardiac ischemia over placebo. ED is most frequently caused by pelvic arterial insufficiency resulting from atherosclerosis, and T administration in men with arteriogenic ED produces robust vasodilator effects on the cavernous arteries. The role of T supplementation on erectile function in the era of phosphodiesterase type 5-inhibitors is discussed. (The Endocrinologist 2005;15: 99 -105) Learning Objectives • Explain the systemic vascular effects of testosterone (T) and the mechanisms by which it counters the vasorelaxant and/or vasoconstrictive changes underlying erectile dysfunction. • Describe how circulating T levels may relate to risk factors for cardiovascular disease. • Compare the possible effects of administering T with other treatments for erectile dysfunction secondary to hypogonadism.N ormal aging is associated with a decrease in total testosterone (T) levels of the order of 0.5% to 2% per year. This age-related T decline may affect either arterial reactivity or sexual function. 1 Hypogonadism in aging men, as defined by a low free testosterone index, is the result of declining testosterone production and increased sex hormone-binding globulin levels. Approximately 20% of men in their 60s and 30% of men aged 70 -79 years may have low testosterone levels. 2 Diagnosis of hypogonadism is based on clinical symptoms (eg, decreased muscle mass, fat mass ratio, bone fractures, loss of libido, and erectile dysfunction ͓ED͔) and laboratory determinations of serum testosterone, usually total T levels. Measuring bioavailable T, or free T, is expensive and time-consuming, but may more accurately detect hypogonadism. The normal range for serum total T levels in early morning hours in healthy, young men, 20 to 40 years of age, is approximatively 300 to 1000 ng/dL (10.5-35 nmol/L). Levels falling below 200 ng/dL (7 nmol/L) clearly indicate hypogonadism and the need for hormone replacement therapy (HRT). Total T levels between 200 and 400 ng/dL (7-14 nmol/L) should be repeate...

Clinical and preclinical treatment of urologic diseases with phosphodiesterase isoenzymes 5 inhibitors: an update

“…Given the important role of testosterone (T) in the sexual activity and decreased plasma level of T in unresponsive subjects, interest in T plus PDE5-Is therapy has increased in recent years. SM cell degeneration (apoptosis), adipose tissue and collagen fibers deposition in CC, and reduced expression of eNOS and neural nitric oxide synthase (nNOS) were confirmed in hypogonadism subjects by previous studies 43444546. Upregulation of CCSM contractility was also found in castrated or diabetic animal models 47484950.…”

Phosphodiesterase 5 Inhibitors in the Treatment of Erectile Dysfunction

“…The role of testosterone salvage in the setting of 'subclinical' hypogonadism of patients with ED has to be assessed again in the presence or absence of PDE5-i effectiveness [83]. Basic studies have demonstrated that androgen deprivation decreases PDE5 expression in the human penis with a related reduction in protein expression [84].…”

Testosterone and phosphodiesterase type-5 inhibitors: new strategy for preventing endothelial damage in internal and sexual medicine?

“…T circulating-levels are determinant for correct endothelial function, and tend to a stepward decrease with aging and with Therapeutic Advances in Urology 1 4the presence of numerous comorbidities [Travison et al 2007]. T plays a key role in coordinating and facilitating the delicate balance between the effect of endogenous vasoconstrictors and vasorelaxing agents of vascular tone [Aversa et al 2005;Thompson and Khalil, 2003]. This process is supported by the fact that androgen receptors (ARs) have been localized within vascular endothelium and smooth muscle-cells.…”