Low Serum Testosterone and Mortality - Part 2

Low Serum Testosterone

In the industrialized world, men experience an earlier onset of cardiovascular disease and a life expectancy 5 to 10 years shorter than women.  Another study evaluated 4152 men and women, the evaluating “Low testosterone concentrations in men contribute to the gender gap in cardiovascular morbidity and mortality”.

The results indicated that men were uniformly at higher risk of incidence for cardiovascular morbidity, including being overweight, hypertension, high cholesterol, metabolic syndrome, and type II diabetes than women.

One particular study examined the association between serum testosterone and estradiol and all-cause mortality in elderly men.  In the conclusion of this study, which included a mean follow-up of 4.5 years, 383 deaths occurred.  Risk of death nearly doubled in subjects with low levels of both testosterone and estradiol compared with other subjects.  In conclusion, it was noted that elderly men with low serum testosterone and estradiol have increased risk of mortality.

The study noted that circulating estradiol levels in older men are low but measurable, exceeding the levels found in postmenopausal women.  It was noted that approximately 80% of circulating estradiol in men derived from androgens and therefore serum levels of estradiol and testosterone were significantly associated.  Studies investigating aromatase or estrogen receptor deficiency in males demonstrated that estradiol had important physiological effects on bone maturation and peak bone mass in younger men.  The role of estradiol in a Swedish Osteoporotic study revealed that low serum estradiol was associated with an increased risk of fracture.

In this study testosterone levels as well as estradiol levels in men were assessed.  Low levels of both testosterone and estradiol independently predicted all-cause mortality in these models.  In subjects with low levels of both testosterone and estradiol, risk of death approximately doubled when adjusted for age, BMI, physical activity and smoking.

The result of the study indicated that risk of death increased in elderly men in the lowest quartile of both testosterone and estradiol levels.  It was also noted that testosterone and estradiol predicted death independently of each other, and risk for death nearly doubled (96% increase) in subjects with both low testosterone and low estradiol compared with subjects within other quartiles of both hormones.

Two major hypotheses regarding the association between low sex steroid levels and mortality were put forward:

± Low sex steroid levels caused or worsened disease and thereby caused death.

± Low sex steroid levels are a result of disease and therefore associated with death.

In this case the second hypothesis, that is the low testosterone/low estradiol levels, is supported by evidence that both acute and chronic illnesses reduce testosterone production.  In acute illness, testosterone is often profoundly depressed at the testicular level and indirectly through gonadotropin suppression.  Therefore, low serum sex steroids may be considered a general marker of poor health and associated with increased mortality risk.

In this study, the association between estradiol/testosterone and mortality remained significant even after deaths were excluded that had occurred within the first 3 years of follow-up, thus arguing against a substantial role of prevalent diseases that otherwise might have been observed during observation.  Therefore, low testosterone levels contribute to frailty that affects the individual’s capability to recover after any disease and thereby affects survival.

In conclusion, low serum testosterone and estradiol were associated with increased risk of death in older Swedish men.  Subjects with low testosterone and estradiol were found to have an increased risk of mortality. Thus, both low testosterone and low estradiol may serve as markers of mortality risk in elderly men.

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