Testosterone replacement therapy in the setting of prostate cancer
treated with radiation
AW Pastuszak
, AM Pearlman
, G Godoy
, BJ Miles
, LI Lipshultz
and M Khera
A lack of consensus and few data support testosterone replacement therapy (TRT) in hypogonadal men who have been treated
for prostate cancer (CaP), particularly those who have received radiation therapy. We performed retrospective review of 13
hypogonadal men with CaP, treated with brachytherapy or external beam radiotherapy who were subsequently treated with
testosterone (T) between 2006 and 2011. Serum T, free T (FT), estrogen (E), sex hormone-binding globulin (SHBG), prostate-speci±c
antigen (PSA), hemoglobin (Hgb) and hematocrit (Hct) values were evaluated approximately every 3 months after TRT initiation up
to 67 months of follow-up. Prostate biopsies demonstrated four men with Gleason (Gl) 6, 7 with Gl 7 and 2 with Gl 8 disease.
Median (interquartile range) age at TRT initiation was 68.0 (62.0–77.0) years, initial T 178.0 (88.0–263.5) ng dl
, FT 10.1 (5.7–15.0)
pg ml
and PSA 0.30 (0.06–0.95) ng ml
. Median follow-up after TRT initiation was 29.7 months (range 2.3–67.3 months).
At median follow-up, a signi±cant increase in mean T (368.0 (281.3–591.0) ng dl
0.012) and SHBG were observed, with no
signi±cant increases in Hgb, Hct, E, FT, or PSA (0.66 (0.16–1.35) ng ml
0.345). No signi±cant increases in PSA or CaP
recurrences were observed at any follow-up interval. TRT in the setting of CaP after treatment with radiation therapy results in a rise
in serum T levels and improvement in hypogonadal symptoms without evidence of CaP recurrence or progression.
International Journal of Impotence Research
24–28; doi:10.1038/ijir.2012.29; published online 13 September 2012
hypogonadism; prostate cancer; radiation therapy; testosterone replacement
Late-onset hypogonadism (LOH) is present in up to 7% of men
70 years old and in up to 18.4% of men
70 years old.
men over the age of 65 years currently account for 5.6% of the
US population, this age group is growing 2–3 times faster
than men
65 years old, suggesting that the prevalence of
LOH will only continue to increase.
Characterized by low
serum testosterone (T), as well as symptoms of androgen
de±ciency, which include loss of libido, erectile dysfunction,
depression, lethargy, concentration dif±culties, sleep distur-
bance, osteoporosis and loss of muscle strength, LOH has
widespread implications on men’s health and has been asso-
ciated with cardiovascular disease, insulin resistance, type II
diabetes and metabolic syndrome.
Treatment with testosterone replacement therapy (TRT) ame-
liorates the symptoms of hypogonadism, but is controversial in
the setting of prostate cancer (CaP) due to the belief that T can
stimulate its growth. A study by Huggins and Hudges
in 1941
demonstrated CaP regression in men with metastatic disease after
surgical castration and subsequent
in vitro
studies showed CaP cell
growth after treatment with T, further supporting the CaP–androgen
Despite these early ±ndings, there remains a dearth
of clinical evidence supporting a link between high serum T and
increased CaP risk. Thus, in the light of mounting evidence sug-
gesting worse health outcomes in men diagnosed with hypogo-
nadism, together with the lack of data supporting a clinical
association between T and CaP growth, TRT has been initiated in
hypogonadal men with CaP.
Most studies examining hypogonadal men receiving TRT after
radical prostatectomy (RP) have described no cases of biochemical
recurrence or evidence of CaP progression in the setting of
localized disease.
Similarly, studies of patients with CaP treated
with brachytherapy and/or external beam radiotherapy (EBRT) and
on TRT have reported transient rises in prostate-speci±c antigen
(PSA), but no patients with CaP recurrence or progression
prompting TRT cessation.
Furthermore, no evidence of bone
metastasis or local recurrence has been observed in hypogonadal
patients with locally advanced CaP who underwent surgical
castration followed by intermittent TRT, nor have there been
signi±cant rises in PSA or evidence of CaP progression in patients
with CaP on active surveillance treated with TRT.
In one study
examining 96 men on TRT after RP, radiation therapy, or
intermittent androgen deprivation, with 8 men demonstrating
evidence of distant metastasis prior to TRT initiation, TRT was
stopped in 60% of men due to rising PSA.
The above small studies overall support the use of TRT in
patients with CaP, irrespective of CaP treatment modality, in the
setting of vigilant follow-up, as does a recent review of the pub-
lished literature, particularly given the known effects of exogenous
T on prostate cell growth
in vitro
However, no published data
from randomized controlled trials studying outcomes of TRT in
treated CaP patients are currently available, and the data from
retrospective studies are limited. In this retrospective study, we
assess the ef±cacy and safety of TRT in a cohort of men with CaP
treated with radiation, with the goal of adding to the literature
describing TRT in men with CaP.
Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA;
Baylor College of Medicine, Houston, TX, USA and
Methodist Urology Associates, The Methodist
Hospital, Houston, TX, USA. Correspondence: M Khera, Scott Department of Urology, Baylor College of Medicine, 6620 Main Street, Suite 1325, Houston, TX 77030, USA.
E-mail: mkhera@bcm.edu
These authors contributed equally to this work.
Received 23 January 2012; revised 5 June 2012; accepted 13 July 2012; published online 13 September 2012
International Journal of Impotence Research (2013) 25, 24–28
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