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L
ate
-
onset
hypogonadism
or
ADAM:
treatment
R
ev
A
ssoc
M
ed
B
ras
2014; 60(5):404-414
407
cer. Short-term studies with few patients suggest that after 1
year of treatment TRT can commence if the patient is cured.
The data available in the literature indicate that:
1.
The incidence of prostate cancer in men with late-on-
set hypogonadism on TRT is no greater than the po-
pulation in general (
B
);
31
2.
TRT in older men with late-onset hypogonadism
seems to have a slight effect on prostate tissue (
A
);
32
3.
In patients with prostate cancer treated using radi-
cal prostatectomy, brachytherapy or radiotherapy,
TRT can be used with caution, and patients should
be constantly monitored (
C
);
27,28
4.
High doses of testosterone, even if associated with
5-alpha-reductase inhibitors, cause a significant in-
crease in PSA (
B
).
30
The greatest risk of prostate cancer has been observed in
men with higher estrone levels (
A
);
33
however, studies with
a higher number of patients should be conducted to con-
firm this observation.
Recommendation
Maintaining testosterone at physiological levels increa-
ses PSA levels, but does not increase the incidence of pros-
tate cancer. Men successfully treated for prostate cancer
and diagnosed with hypogonadism are candidates for
TRT after a prudent interval for observation, and there
is no clinical or laboratory evidence of recurrence of the
disease. The risks and benefits of TRT should be clearly
understood by the patient and treatment should be care-
fully monitored. The safety data in this clinical situation
are still limited. Maintaining physiological serum levels
of testosterone and monitoring PSA in all patients on tes-
tosterone replacement is recommended.
W
hat
is
the
role
of
ART
in
the
increased
risk
of
cardiovascular
disease
?
The effects of TRT on cardiovascular risk appear to be as-
sociated with the adverse effects on polycythemia, lipid
profile and sleep apnea. On the other hand, TRT leads to
a decrease in BMI and improves the lipid profile, provi-
ding cardiovascular benefit (
B
).
31
The maintenance of se-
rum testosterone levels within the normal range does not
lead to significant changes in hemoglobin and lipid pro-
files, decreasing the risk of developing polycythemia and
consequently cardiovascular and vascular events (
B
).
34,35
Hyperinsulinemia and insulin resistance (IR) are es-
sential components of metabolic syndrome, which in
turn is associated with an increased cardiovascular risk.
TRT improves the components of metabolic syndrome
metabolic syndrome can lead to (yet unproven) benefits
for their metabolic state (
B
).
2
There is speculation about the role of the age-related
decrease in DHEA on the metabolism of carbohydrates.
The few studies that have addressed this issue suggest that
DHEA has no effect on the metabolism of carbohydra-
tes (
B
).
25
Recommendation
The effects and benefits of testosterone replacement on
the metabolism of carbohydrates and lipids are still con-
troversial. Testosterone replacement is recommended
in men with ADAM and metabolic syndrome as an ad-
junctive to improve the metabolic profile of such pa-
tients.
W
hat
is
the
risk
of
ART
in
relation
to
exacerbating
prostate
disease
?
Unfortunately, to date there is no consensus on the res-
ponse pattern of PSA to testosterone therapy. It has been
argued that a significant increase in PSA after beginning
testosterone replacement can be a sign of prostate can-
cer. However, most studies do not support this argument.
Historically, TRT has been absolutely contraindica-
ted in men with a suspected or confirmed diagnosis of
prostate cancer. There is evidence that TRT can stimula-
te growth and aggravate the symptoms of prostate can-
cer in men with active disease.
TRT causes a mild increase in PSA in most patients
without prostatic changes and such increase does not
depend on patient age, mode of replacement, or baseli-
ne PSA levels and total free testosterone (
B
).
26
In intra-
-prostatic cancer patients with normalization of PSA af-
ter permanent brachytherapy or external beam radiation
therapy who developed hypogonadism, testosterone treat-
ment determined a slight increase in PSA with no signs of
recurrence or progression of the cancer (
C
),
27,28
while in
those submitted to radical prostatectomy, PSA levels did
not change (
B
).
29
In all these studies, testosterone levels
were maintained within the normal range. On the other
hand, when serum testosterone levels are kept above the
normal values in patients previously treated for prostate
cancer, even with the association of 5
-
a
-
reductase inhi-
bitors, PSA levels rise significantly (
B
).
30
In patients who received curative treatment for low risk lo-
calized prostate cancer with the radical prostatectomy and/or
radiotherapy, with no evidence of active disease, the risks
and benefits of TRT should be assessed. There is no con-
sensus on the moment for determining consolidated hea-
ling treatments with this intention in localized prostate can-