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M
artits
AM
et
al
.
412
R
ev
A
ssoc
M
ed
B
ras
2014; 60(5):404-414
to maintain physiological and stable levels of serum testos-
terone and DHT (
B
)
59
and have similar effectiveness and sa-
fety as other injectable forms (
B
)
58,63
(
D
).
64
The advantage of
TUD is that with only 4-5 injections per year testosterone
levels can be maintained at physiological levels (
B
).
15
TUD appears to have a role in the treatment of me-
tabolic syndrome. A follow-up of patients with metabo-
lic syndrome and ADAM using TUD for a period of one
year showed that testosterone levels were restored to the
normal average value. There was a significant improve-
ment in sexual symptoms, metabolic syndrome parame-
ters and body composition. There was no change in PSA,
blood glucose and liver function, and the levels of hemo-
globin and hematocrit did not exceed the upper limit of
a normal range (
A
)
36
(
B
)
38
(
C
).
16
The increase in blood pressure, hematocrit > 50% and
worsening lipid profile that may occur in a small number
of patients were related to the number of CAG repeats of
the androgen receptor and the presence of obesity (
B
).
57
ART with long acting TU proved to be safe for a period
of 24 months of treatment.
Recommendation
The main role of long acting testosterone is maintenance of
physiological serum testosterone levels with a lower number
of applications and consequently lower rate of side effects.
I
s
there
a
difference
in
absorption
between
the many
pharmacological
preparations
?
Each formulation has a distinct characteristic, depending
on the presentation, dose and pharmacokinetics. The tes-
tosterone esters used in short acting injectable formula-
tions are derived from fatty acids and depend on the es-
ters being releases from the oily vehicle and the
hydrolysis of these esters in order to release of testoste-
rone into the circulation. The pharmacokinetics are de-
termined in part by the size of the side chain, hence the
wide variation in the use of different esters modulates the
level of circulating testosterone (
D
).
41
The testosterone levels obtained with short acting in-
jectable forms are unstable (
B
),
55,61
whereas long acting
injectable forms provide more stable levels.
In the oral formulations, absorption is variable and
bioavailability is generally poor due to the effect of first
passing through the liver. Oral testosterone undecanoate
is preferentially absorbed by chylomicrons, avoiding the
liver. However, the testosterone level is sub-optimal and
it must be taken various times per day (
D
).
41
The oral mucosa patches and sublingual formula-
tion are not often used. The first seems to have a good
absorption similar to that of gels, but a shorter half-li-
fe, requiring use twice per day
(
B
).
43
Transdermal pat-
ches are presented in formulations that vary in size and
thus the dose of testosterone. Studies indicate that ab-
sorption is efficient and reaches equilibrium in 48 hours
(
B
).
44
The absorption of scrotal patches is more efficient
because the skin is thinner and increased production of
DHT occurs because the amount of 5 alpha reductase
in that region is higher
(
D
).
41
The evening application
of the patch produces serum testosterone mimicking
the circadian rhythm of healthy men, while the appli-
cation of the gel in the morning produces physiological
and stable serum testosterone levels (
B
),
15,46,55,61
which
shows the different absorption mechanisms between
the two formulations.
Recommendation
The differences in absorption between the various phar-
maceutical forms depend on the presentation, dose and
pharmacokinetics. Testosterone levels obtained by short
acting injectable forms and oral forms are more unstable
and less physiological. On the other hand, the levels ob-
tained by means of injection and for long acting trans-
dermal forms are stable and physiological. The only phar-
maceutical form that mimics the circadian rhythm is that
of scrotal patch. The preferential use of the long acting
injectable form or transdermal forms is recommended
for ART.
W
hat
are
the
contraindications
for
ART?
An increased risk of cardiovascular events has been ob-
served in elderly patients with ADAM associated with
other chronic diseases.
The administration of testosterone is contraindica-
ted in men with prostate or breast cancer, in men with
palpable prostate nodules or PSA greater than 4 ng/mL
or 3 ng/mL in high risk patients (
D
).
41,48
ART is recommended to be applied with caution in
men with benign prostate hypertrophy and mild or mo-
derate urinary symptoms, while men with severe urinary
symptoms should undergo urologic evaluation before
starting treatment.
Testosterone should not be used in men with hema-
tocrit > 50% or patients with grade III or IV CHF. Men
with moderate or severe obstructive sleep apnea should
be evaluated by a specialist before starting ART (
D
).
48