NATURE REVIEWS

UROLOGY

VOLUME 11

SEPTEMBER 2014

529

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;

0.012),

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

and colleagues.

In these seven studies

29–35

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

prostatectomy.

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

et al.

retro-

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

4 disease.

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.

Furthermore,

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.

Conclusions

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

patients.

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.

12–17

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

the patient.

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 (

J.M.D.

G.M.L.

M.K.

L.I.L.

Correspondence to: L.I.L.

larryl@bcm.edu

Spitzer, M., Huang, G., Basaria, S.,

Travison, T. G. & Bhasin, S. Risks and benefits

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Cancer Res.

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Morgentaler, A.

et al.

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in men with untreated prostate cancer.

J. Urol.

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et al.

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[online],

https://www.auanet.org/about/

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Eur. Urol.

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et al.

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‘‘

…no clear guidelines are

available to facilitate decision-

making regarding the use of TST

in men with prostate cancer

’’

PERSPECTIVES