Androgens in Health and Disease.pdf - E Library

Chapter 13/Androgens and Body Composition 249
In summary, these studies, along with others (25), show that administration of testosterone
at supraphysiologic doses to normal men can lead to increases in lean body mass
and reductions in fat mass. Supraphysiologic testosterone administration may result in
some increases in strength, although more significant effects on strength are achieved in
the setting of a combined exercise program (23). Further studies are necessary to determine
the potential adverse effects of supraphysiologic testosterone use on the prostate
gland, hepatic function, lipids, and erythrocytosis.
The effects of testosterone on muscle mass are the result of increased muscle protein
synthesis, as determined by infusion of stable leucine isotope infusions and muscle
biopsies (24). Effects of testosterone on whole-body protein synthesis using leucine flux
experiments have been unremarkable, perhaps because of the relative low level of muscle
protein synthesis vs total-body synthesis (23,24).
ARE THERE APPLICATIONS OF TESTOSTERONE IN CHRONIC ILLNESS?
Because of the effects of testosterone in enhancing fat-free mass and muscle size, it
has been suggested that there may be a role for testosterone in promoting lean body mass
in catabolic states. In addition to aging, chronic illnesses such as HIV infection, chronic
renal failure, and chronic obstructive lung disease are associated with testosterone
deficiency, as are subjects receiving long-term supraphysiologic glucocorticoid administration
(26–28). These situations are also associated with muscle loss, suggesting a role
for testosterone administration in promoting muscle mass and, potentially, muscle function
in these situations.
Elderly Men and Sarcopenia: A Role for Testosterone?
Aging is associated with specific alterations in body composition. There is an approx
33% reduction in muscle mass between the ages of 30 and 80 yr, and this loss increases
to 1% per year after the age of 70 yr (29). This sarcopenia leads to diminished strength
and function. Isometric and dynamic maximal voluntary strength of the quadriceps
muscles decreases after the age of 50 yr and there is an approx 30% decrease in strength
between 50 and 70 yr (30). Muscle weakness is a common feature in elderly subjects who
fall, a common cause of accidental injury and fracture in the elderly (31,32). Aging is also
associated with an increase in general adiposity, with specific deposition in the central,
visceral area (33,34). Because central adiposity is associated with hyperinsulinemia and
enhanced cardiovascular risk, it is important to determine whether there are factors that
may underlie these changes in body composition that may be reversible.
Multiple studies have demonstrated a decrease in serum testosterone levels in men
with age (35–37), although others have not (38). Mean testosterone levels in men aged
80 yr are approx 60% of the level for men 25–50 yr (39). The similarity of changes in
muscle composition between castrate animals, hypogonadal men, and aging men suggests
a role for relative hypogonadism in the decline of muscle composition/performance
and the increase in adipose stores in the elderly (40). In a community-based study
of 775 older men, impaired glucose tolerance, assessed by oral glucose tolerance test
(OGTT), and fasting plasma glucose were associated with lower total-testosterone levels
(41). These data suggest that relative testosterone insufficiency in elderly men may be
associated with heightened cardiovascular risk.
There have been several studies evaluating the effects of testosterone replacement on
body composition in elderly men. These studies have included subjects with serum