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Aging and plasma lipids and lipoproteins |
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 Top Aging and plasma lipids... References |
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In contrast, large epidemiological studies show that plasma HDL levels in elderly men are actually slightly higher than in middle-aged men (2). One explanation for this phenomenon is that individuals with lower HDL levels succumb to atherosclerotic disease earlier in life so that, by a process of elimination, men with higher levels of HDL cholesterol tend to survive to older age. Alternatively, higher HDL levels in older men could be associated with the age-related decline in circulating androgens. Again, in contrast to the pattern seen in women, LDL levels in men increase slowly but progressively from the late teenage years to the mid 50’s, at which point they become relatively constant. In the Lipid Research Prevalence study (2), mean LDL levels in women over the age of 60 were in fact slightly higher than mean levels seen in men of the same age.
Effects of T on plasma lipids and cardiovascular risk
The majority of cross-sectional studies of androgens and plasma HDL levels show a positive relationship between serum T levels and corresponding levels of HDL cholesterol (reviewed in 1). In contrast, most studies of T administration in young, hypogonadal or eugonadal men demonstrate a decrease in HDL cholesterol of 5–15% as T levels are raised (1); the magnitude of decrease has tended to be greater in subjects with higher baseline levels of HDL. In general, plasma LDL and triglyceride levels have remained unchanged in these experimental paradigms. Recent data suggest that in young men, supraphysiological levels of T may also suppress levels of lipoprotein (a) [Lp(a)], which is generally acknowledged as an independent risk factor for coronary artery disease. As with HDL, this effect is most noticeable in subjects with high baseline levels (3). Thus, the net effects of T on plasma lipids are complex and may vary from individual to individual, depending in part on that person’s baseline lipoprotein profile.
Clearly there is a discrepancy between the results of the cross-sectional and interventional studies of the association between androgens and lipids. However, both HDL cholesterol and testosterone may be influenced by multiple factors including disease states, lifestyle (for example smoking, exercise), and factors such as body mass index, fat distribution, and waist-to-hip ratio. In general, factors that decrease HDL cholesterol also decrease testosterone levels. It is therefore possible that such factors could explain the population findings that men with higher T levels also have higher levels of HDL cholesterol and lower levels of triglycerides.
It should be noted that the aforementioned changes in plasma lipids are in response to administration of aromatizable androgens such as T enanthate or T cypionate. When nonaromatizable, particularly oral, androgens such as stanozolol or methyltestosterone are administered, HDL levels decrease profoundly whereas LDL levels increase significantly (1). There are several case reports of stroke and myocardial infarction in young users of high doses of nonaromatizable androgens (4).
In addition to their effects on lipids, androgens may serve as regulators of other factors contributing to cardiac risk. In animals, androgens act as vasodilators (5), but in the human male, plasma levels of the vasoconstrictor endothelin are higher than in the female (6). Visceral fat accumulation is generally believed to increase risk for atherosclerotic disease. A few recent studies have shown that, in both young and middle-aged men, androgen administration is associated with a reduction in visceral fat accumulation in the abdomen (7, 8). In one very recent report, lower T levels were predictive of increases in abdominal fat in normal men assessed prospectively over 7.5 yr (9).
T administration and cardiovascular risk in older men
There are relatively few data regarding T effects on cardiovascular risk factors in older men. In one long-term study of a very low dose of T cypionate (25 mg im, weekly for 4 yr) HDL cholesterol levels did not change during treatment, and total and LDL cholesterol levels decreased significantly (10). Studies of higher doses of T, used for shorter periods of time, have also demonstrated significant decreases in total and LDL cholesterol levels (11, 12, 13). In these studies, HDL cholesterol levels were either unchanged or showed a nonsignificant decrease in response to the higher ambient T levels. It is presently unknown whether androgens have a different mechanism of action on plasma lipids in older men than in younger men.
Also unknown at this time is the effect of T on abdominal fat depots in older men. T administration is associated with a modest decrease in total body fat (11), but more specific studies are needed to determine whether the visceral abdominal fat depots associated with increased risk of coronary artery disease are also reduced.
Cardiovascular disease is a major cause of morbidity and mortality in older men. Before androgen replacement can be considered truly "safe" for this population, it will be important to examine the long-term effects of T replacement on plasma lipids, lipoproteins such as Lp(a), and body fat distribution, specifically in older men. It will also be important to analyze the incidence of cardiovascular events in men who receive androgens for extended periods. The available data suggest, however, that from the cardiovascular perspective, judicious administration of aromatizable forms of T is likely to be safe for the majority of older hypogonadal men.
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