Are Declining Testosterone Levels A Major Risk Factor for Ill-Health in Aging Men?

B. B. Yeap


April 08, 2009

In This Article

Testosterone, Cardiovascular Risk and Mortality in Aging Men

Erectile dysfunction is a marker for impaired endothelial function and underlying vascular disease and its presence predicts increased incidence of subsequent cardiovascular disease events[96,97,98] (Table 3). This association between erectile dysfunction and cardiovascular risk is complex as erectile dysfunction commonly coexists with conditions that are associated with increased risk of cardiovascular disease, namely obesity, metabolic syndrome and Type II diabetes, which are also associated with lower testosterone levels.[80,81,97,99] Thus, lower testosterone levels are associated with higher body mass index (BMI), and with increased prevalence and incidence of metabolic syndrome and Type II diabetes in middle-aged and older men.[10,11,13,14,19,100,101,102,103,104,105,106,107] In addition, lower testosterone levels are associated with surrogate markers for cardiovascular disease, including less favorable carotid intima medial thickness,[108,109,110] ankle/brachial index as a measure of peripheral arterial disease[111] and calcific aortic atheroma.[112] Thus, lower testosterone levels, erectile dysfunction and conditions associated with higher cardiovascular risk appear to be interrelated.[113,114] The direction of causation is debatable as marked obesity predisposes to type II diabetes and atherosclerosis, and may reduce LH pulse amplitude and testicular responses to LH.[115,116] However, testosterone therapy increases lean body mass and reduces fat mass, thus modulating insulin resistance and risk of metabolic syndrome.[66,117,118] Testosterone may also exhibit antiatherogenic effects at the tissue level, whether mediated by classical or nonclassical pathways.[119,127,128] The key question is whether testosterone therapy reduces the risk of cardiovascular disease distinct from any effects on erectile dysfunction. Trials of testosterone therapy generally have not been designed or adequately powered to detect effects on clinically significant cardiovascular events.[16,64,65,66,119,120] Although randomized controlled trial data are lacking, there are observational data which support a relationship between low testosterone and fatal cardiovascular events. Lower testosterone levels have been associated with increased overall and cardiovascular-related mortality in middle-aged and older men.[121,122,123] However, other studies have not shown a clear relationship between lower testosterone and higher mortality.[124,125] In the Caerphilly study, a higher ratio of cortisol to testosterone was associated with ischemic heart disease but this was attenuated after adjustment for components of the insulin-resistance syndrome.[124] By contrast, in the Massachusetts Male Aging Study, higher free testosterone was significantly associated with ischemic heart disease mortality.[125] Finally, data are lacking as to whether higher testosterone levels predict reduced incidence of combined nonfatal and fatal major cardiovascular events.[126] Thus, although lower testosterone levels are associated with higher cardiovascular risk and to an extent with mortality in aging men, randomized controlled clinical trials of adequate size and duration are needed to determine whether testosterone therapy will reduce morbidity and mortality from cardiovascular disease in hypogonadal or eugonadal men.