TST and prostate cancer risk
In men without prostate cancer
If elevated testosterone levels are associ-
ated with an increased risk of prostate
cancer, analysis of data from clinical trials
performed to evaluate the efficacy of TST
should provide useful insight into the
relationship between TST and the incidence
of prostate cancer among men at histori-
cally average risk of this disease. With this
in mind, a meta-analysis of 19 placebo-
controlled TST studies in men with low
or low–normal serum testosterone levels
found no statistically significant difference
in prostate cancer incidence, PSA levels, or
urinary symptom scores in men treated with
TST, compared with placebo.
Pooled mean
testosterone levels for the men included in
these studies before therapy were 344 ng/dl
and 320 ng/dl for placebo and testosterone
treated groups, respectively;
after treat-
ment, mean testosterone levels were
339 ng/dl and 536 ng/dl, respectively.
both groups, the initial serum PSA level
was 1.3 ng/dl, and men in the TST cohorts
of the studies analysed had an increase in
PSA of only 0.3 ng/dl, on average, after
This meta-analysis demon-
strated a pooled event rate for the diagno-
sis of prostate cancer of 8.3 and 9.2 events
per 1,000 patient-years for patients treated
with placebo and testosterone, respectively
(OR 1.09, 95% CI 0.48–2.49).
In addition,
events constituting either an increase in
serum PSA of ≥1.5 ng/ml or achievement
of a PSA level >4 ng/ml was identified at
a frequency of 41.6 and 57.1 events per
1,000 patient-years for the placebo-treated
and testosterone-treated patients, respec-
tively (OR 1.19, 95% CI 0.67–2.09). In
addition, a review of seven published trials
evaluating TST found the rate of prostate
cancer in testosterone-treated patients to be
similar to the rate observed in population-
screening trials.
Together, these findings
suggest that TST therapy has a limited, if
any, clinically relevant effect on prostate-
cancer risk in individuals with low–normal
baseline testosterone levels.
In men at risk of prostate cancer
Patients with HGPIN detected in a single
sextant prostate biopsy sample have a
25–30% chance of a prostate cancer diag-
nosis upon subsequent biopsies. García-
et al.
prospectively analysed 82
men diagnosed with HGPIN, and found
a signifi cant positive correlation of both
low bioavailable—unbound or albumin-
bound (that is, testosterone not bound to
high-affinity testosterone-binding proteins
such as sex hormone-binding globulin)
—testosterone and low free serum testos-
terone levels in serum with a subsequent
prostate-cancer diagnosis (
0.04 for both
free and bioavailable testosterone). This
finding provides further evidence indicat-
ing that low serum testosterone, rather than
high testosterone levels, might be a risk
factor for prostate cancer.
Additionally, Rhoden
et al.
75 hypogonadal men treated with TST for
12 months; all the men included underwent
a prostate biopsy before beginning TST, and
20 men had HGPIN based on this initial
After a 1-year follow-up period,
the investigators found no statistically
signifi cant change in PSA levels in men
with normal biopsy results versus men with
evidence of HGPIN in the initial biopsy
One patient with HGPIN was
later found to have prostate cancer based
on an abnormal DRE.
The authors con-
cluded that hypogonadal men with HGPIN
on biopsy did not have an increased risk
of prostate cancer after TST compared to
men with a normal prostate biopsy.
data suggest that TST does not increase the
incidence of prostate cancer, even among
individuals with a high-risk of developing
the disease.
In men treated for prostate cancer
Much controversy regarding TST is focused
on concerns over the safety of testosterone
administration in men who have previ-
ously been treated for prostate cancer.
Considering the demographical similari-
ties between patients with prostate cancer
and hypogonadal men, that some men
have both conditions is not surprising.
Traditionally, patients with prostate cancer
have been considered ineligible for TST,
but studies published over the past decade
suggest that TST for hypogonadism can be
safe when given to carefully selected and
monitored patients.
Men can receive definitive treatment for
prostate cancer with radical prostatectomy,
or with brachytherapy or external beam
radiation therapy (EBRT). With regard to
patients treated with radical prostatectomy,
et al.
retrospectively reviewed
103 hypogonadal patients who received
transdermal TST after surgical treatment
of prostate cancer between 2003 and 2011.
The authors also included 49 eugonadal
patients also treated with radical prosta-
tectomy, but not with TST, as a reference
group, and categorized all patients as being
at high risk or low risk of postoperative
prostate-cancer recurrence.
High risk
of recurrence was defined as postsurgical
pathology findings of one or more of the
following: Gleason score ≥8, positive sur-
gical margins, or positive lymph nodes.
Overall, the TST and eugonadal control
populations had similar proportions of
high-risk patients (25% versus 30%).
hypogonadal patients had an initial median
serum testosterone level of 261 ng/dl, which
increased to 460 ng/dl during the course of
After a median follow-up duration of
27.5 months, a small increase in serum PSA
of 0.003 ng/dl (
<0.001) was detected in the
hypogonadal patients as a whole, with no
increase in PSA levels in the eugonadal ref-
erence group.
In the hypogonadal cohort,
four cases of biochemical recurrence were
observed, compared with eight cases in the
reference group of eugonadal men.
TST in men who have previously received
definitive brachytherapy for prostate cancer
has been evaluated by Sarosdy.
author studied 31 men with serum testos-
terone levels of <300 ng/dl and symptoms
of hypogonadism, in whom TST was ini-
tiated at least 6 months after brachyther-
apy, with most patients receiving weekly
200 mg injections of testosterone cypio-
Patients were followed for a median
of 5 years (range 1.5–9.0 years), with serum
testosterone levels increasing from a median
of 188 ng/dl before TST to 498 ng/dl at
follow-up assessment.
One patient dem-
onstrated a single rise in serum PSA, which
was followed by a decline in PSA.
signs of cancer recurrence were observed
in this patient group and, therefore, no
patients stopped TST because of possible
or confirmed cancer recurrence.
In addition, Pastuszak
et al.
tively studied data from three men who
were treated with brachytherapy for pros-
tate cancer, as well as 10 men who were
treated with EBRT. All the men had symp-
toms of hypogonadism and serum testos-
terone levels of <300 ng/dl, and 12 were
sub sequently treated with transdermal
testosterone whereas the remaining patient
received testosterone pellets.
At a median
These data suggest that TST
does not increase the incidence
of prostate cancer, even among
individuals with a high-risk of
developing the disease
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