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TESTOSTERONE AND METABOLIC CHANGES IN MEN WITH ABDOMINAL OBESITY
Stefan Arver
Centre for Andrology and Sexual Medicine, M52, Karolinska University
Hospital, Se-14186 Stockholm. arver@medhs.ki.se
Central or visceral obesity is recognised as a main risk factor for
cardiovascular disease and type II diabetes mellitus. The co-existence
of visceral obesity, increased blood lipid levels, hypertension
and impaired glucose tolerance defines the metabolic syndrome that
today is widely recognised as one of the prime factors behind cardiovascular
morbidity and mortality. Apart from a general imbalance in energy
intake and expenditure, specific mechanisms seem to enhance or suppress
accretion of abdominal fat. Endocrine messages transmitted by catabolic
i.e. corticosteroids and anabolic signals i.e. androgens, growth
hormone -IGF and to some extent estradiol play an important role
in regulating abdominal obesity. Epidemiological studies have in
fact implicated that it's not overweight but rather the amount of
intra abdominal adipose tissue that causes an increased morbidity
and mortality. The primary event that triggers the initial development
of visceral obesity is not known and it seem of great importance
to understand the series of mechanisms that control the process
from recruitment of stem cells to adipogenic commitment, and further
the maintenance mechanism that impacts on continued accretion if
lipids into matured adipocytes. It is well known that glucocorticosteroids
favour relocation of fat from peripheral pools to the abdominal
cavity - a mechanism that make sense in life threatening caloric
compromised situation, as abdominal fat is more readily mobilised.
In a state of normal or excessive nutrition, abdominal fat seem
on the other hand to act as a disease facilitating factor,
Testosterone in men has a key role in the regulation of body composition
and stimulates muscle accretion and suppresses fat accumulation.
The complete mechanism behind this is not known though some important
observations have been made recently. From a series of reports it
seem clear that treatment of men with testosterone deficiency decreases
fat mass (both subcutaneous and intra abdominal fat) and increase
lean mass i.e. muscle mass. Other studies have indicated that a
decrease in testosterone levels, commonly seen in middle age and
elderly men, either coincides with an increase in BMI or increase
the tendency to accumulate abdominal fat.. Thus there might be factors
associated with the loss of testosterone action that cause a susceptibility
to abdominal fat accretion as well as factors associated with increased
BMI and increased abdominal fat that suppresses testosterone levels.
Taken together these two mechanism may form a viscous circle placing
the afflicted man in a point of no or difficult return. The question
of the hen and the egg may not be crucial as there is a scenario
that develops whichever entrance to further development of abdominal
fat that puts the subject into the viscous circle.
A key mechanism triggered by increased abdominal fat mass is a state
of insulin resistance. This cause hyperglycemia and a series of
other metabolic derangements. From an androgen perspective insulin
resistance hampers testosterone secretion by depressing Leydig cell
responsiveness to gonadotropins and further decreased testosterone
amplifies insulin resistance. Central mechanism may also be involved
that suppresses gonadotropin signalling and it has been suggested
that increased activity in the CRF-ACTH-Cortisol axis by various
stress signals depresses the gonadotropin and gonadal axis. Lowering
testosterone also impacts on insulin, and probably on other mechanism
that decreases insulin sensitivity.
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