20 / 111
M
artits
AM
et
al
.
408
R
ev
A
ssoc
M
ed
B
ras
2014; 60(5):404-414
in hypogonadal patients with T2DM, reducing the car-
diovascular risk (
A
).
36
Recommendation
There is no evidence that TRT per se increases cardiovas-
cular risk. It is recommendable to maintain serum tes-
tosterone levels within the normal range so that cardio-
vascular risk factors such as polycythemia and insulin
resistance are minimized, thereby reducing overall car-
diovascular risk.
W
hat
is
the
risk
of
polycythemia
on
ART?
Secondary polycythemia is a major adverse event of TRT.
Several authors have demonstrated its occurrence, and it
is related to the maintenance of high serum levels of tes-
tosterone, regardless of the treatment time (
B
).
31,34,35
The-
refore, the evidence available so far indicates that the
maintenance of serum testosterone levels within the nor-
mal average does not lead to polycythemia (
B
).
37
Recommendation
The appearance of polycythemia is directly related to su-
praphysiological serum testosterone levels. It is recom-
mended to monitor hemoglobin and hematocrit in all
patients on TRT and to maintain serum testosterone le-
vels within the normal range to minimize the risk of
polycythemia.
W
hat
is
the
hepatotoxicity
of
ART?
Hepatotoxicity due to TRT is a rare event limited almost
exclusively to the use of oral 17
a
-alkylated preparations
such as fluoxymesterone and methyltestosterone, which
are highly hepatotoxic and can cause the development of
hepatocellular adenomas, liver carcinomas, cholestasis
and hemorrhagic cysts of the liver (
A
).
1
The long term
use of other testosterone preparations does not lead to a
change in hepatic function among men with late-onset
hypogonadism (
B
).
31,35
Recommendation
17
a
-alkylated oral preparations such as methyltestoste-
rone and fluoxymesterone present hepatotoxicity. It is
not recommended to monitor the liver function of pa-
tients on TRT with any other pharmaceutical form.
W
hat
is
the
effect
of
ART
on
sleep
apnea
? A
re
there
other
side
effects
?
Testosterone replacement has been associated with the
onset or worsening of sleep apnea in men treated with
high doses of testosterone (
A
).
1
The administration of
testosterone in patients with sleep apnea and erectile dys-
function associated with low testosterone improves se-
xual symptoms and does not worsen sleep apnea (
C
).
38
Gynecomastia is a benign, infrequent and generally
reversible complication, a result of the aromatization of
testosterone into estradiol in peripheral tissues. Inferti-
lity and decreased testicular volume are related to supra-
physiological doses of testosterone. Sodium and water
retention may occur during replacement and generally
present clinical significance in patients with cardiac de-
compensation, hypertension or renal failure. Skin reac-
tions such as erythema and itching are common with the
use of patches. Intramuscular injections may cause lo-
cal pain, lumps, rashes and boils. Acne, oily skin, increa-
sed body hair and skin “flushing” are benign and reversi-
ble complications that do not cause major concern (
A
).
1
Recommendation
The side effects of TRT, such as worsening or onset of
sleep apnea, gynecomastia, infertility, fluid retention and
skin changes are directly related to supraphysiological le-
vels of serum testosterone. It is strongly recommended
to maintain serum testosterone levels within the average
normal range to minimize the occurrence of these side
effects.
W
hat
is
the
role
of
ART
in metabolic
syndrome
?
The maintenance of serum testosterone levels within the
normal range leads to improvements in the markers of
metabolic syndrome, such as waist circumference, and
increased levels of HDL without causing polycythemia
or changes in prostatic parameters. This improvement is
not as significant when testosterone levels are maintai-
ned at the lower limit of normality (
B
).
37
TRT does not
depend on the pharmaceutical form of testosterone used
or the route of administration and is effective to impro-
ve metabolic syndrome parameters; when testosterone le-
vels are maintained within a normal range, however, the
improvement is more significant (
B
).
39
In T2DM patients,
TRT reduces insulin resistance, improves glycemic con-
trol, and reduces visceral adiposity and total cholesterol,
which are all components of metabolic syndrome (
A
).
36
The beneficial effects of ART on metabolic syndrome
components appear to be specific to testosterone, given
that chronic replacement with DHEA does not improve
the secretion or action of insulin and postprandial glyce-
mia in women and elderly men (
B
).
40