follow-up period of 29.7 months after initia-
tion of TST, a significant increase in serum
testosterone was observed in the cohort
(from 178.0 ng/dl to 368.0 ng/dl;
but no statistically significant increases
in PSA and no cases of prostate-cancer
recurrence were detected.
To date, seven studies involving TST in
men previously treated for prostate cancer
have been published, as reviewed by Khera
In these seven studies
a pooled sample of 226 men received TST
after undergoing treatment for prostate
cancer, among whom four subsequent
biochemical failures were documented.
This represents a biochemical-failure
rate of 1.8%, which is lower than the rate
observed in a published series of patients
with prostate cancer and favourable disease
parameters who were treated with radical
Overall, these findings
suggest that TST for hypo gonadism is
safe in men previously treated for prostate
cancer, and does not increase the risk of
prostate cancer recurrence.
TST in untreated prostate cancer
The use of TST might be most controver-
sial among patients with untreated prostate
cancer, owing to concerns that exposure
to exogenous testosterone might exacer-
bate this androgen-dependent malignancy.
However, preliminary data from small case
series suggest that TST can be safe even in
such patients, provided administration of
testosterone is restricted to appropriately
selected men, under careful supervision.
Possible selection criteria could include:
consideration of the severity of the hypo-
gonadal symptoms; patient preference after
explanation of the relative potential risks
and benefits; Gleason score; the trajec-
tory and rate of changes in PSA levels;
treatment type; surgical-margin and lymph-
node status; and timing since treatment of
prostate cancer. Morgentaler
spectively evaluated 13 men who elected
for active surveillance of prostate cancer
and also received TST; 12 men had Gleason
6 disease, and one man had Gleason grade
After a mean duration of TST
of 23.5 months, with all patients receiv-
ing a minimum of 9 months of therapy, no
statistically significant change in serum
PSA levels, no change in prostate volume,
and no cancer progression was observed in
any of the 13 men studied.
upon follow-up biopsies, no evidence of
cancer was seen in 54% of specimens.
The body of literature on TST in men with
untreated prostate cancer remains limited,
however, and a smaller study by Morales
that revealed a more variable PSA response
after TST among seven patients with pros-
tate cancer who were undergoing active
surveillance reinforces the importance of
close monitoring of such patients.
Studies published over the past decade
provide strong evidence in opposition to
the generations of urological dogma sug-
gesting that testosterone supplementation
causes prostate cancer to progress. Founded
in the prostate-saturation model, data
accrued in the contemporary era of PSA
testing support the concept that the pros-
tate ARs are saturated at serum testoster-
one levels between 150 ng/dl and 200 ng/dl,
and that additional serum testosterone has
limited, if any, effect within the prostate.
Indeed, a wealth of studies indicates that
TST does not affect prostate size, intrapros-
tatic testosterone levels or prostate-cancer
progression, provided that a patient’s base-
line serum testosterone is >150–200 ng/dl.
TST does not seem to have a marked impact
on serum PSA levels beyond an increase of
0.3 ng/dl over baseline levels in the first
year after TST.
Moreover, no evidence is
available that suggest TST promotes the
initiation of prostate cancer in hypogonadal
men, even those with concomitant HGPIN,
who are at high-risk of prostate cancer. In
addition, 226 men who received some form
of TST following prostate-cancer treatment
have been reported in the literature to date,
and a low prostate cancer recurrence rate
of 1.8% was demonstrated among these
Together, these observations
suggest that TST neither causes nor exacer-
bates prostate cancer, in most cases; some
findings even suggest the contrary: that low
serum testosterone might be a risk factor
for development of prostate cancer.
Nevertheless, it should be recognized that
the literature on this subject is based on a
relatively small group of patients, and TST
in patients with prostate cancer should only
be administered in the setting of carefully
monitoring and after a thorough discus-
sion of the potential risks and benefits with
In summary, no clear guidelines are avail-
able to facilitate decision-making regarding
the use of TST in men with prostate cancer.
However, we believe that consideration of
the severity of the patient’s hypogonadal
symptoms, the impact of this condition
on quality of life, and the potential risks
and benefits of treatment is important.
Additional factors to consider in allocating
TST are Gleason score, PSA trajectory, treat-
ment type, surgical-margin and lymph-node
status, as well as the timing since treatment
of prostate cancer. With regard to timing
since prostate-cancer treatment, we prefer to
wait until at least 6 months after local treat-
ment to allow for stabilization of PSA trends
and convalescence in surgical patients. We
do consider TST in men on active surveil-
lance for prostate cancer, as long as the
patients have a thorough understanding
of the risks and benefits of this approach.
Importantly, all patients with prostate cancer
receiving TST should be evaluated regularly
for monitoring of treatment effectiveness,
adverse effects of therapy, and cancer status.
Scott Department of Urology, Baylor College
of Medicine, 6624 Fannin Street, Houston,
TX 77030, USA (
Correspondence to: L.I.L.
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…no clear guidelines are
available to facilitate decision-
making regarding the use of TST
in men with prostate cancer
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