© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
metabolites, including estradiol, a sex hormone with
major influence on male bone density.
53
Improvements inTRT formulations and refinements
in delivery systems allow more individualization of
TRT. In particular, the availability of higher-potency,
lower-volume transdermal formulations address the
important problemof skin-to-skin transfer of hormone.
Yet patients must be cautioned about this risk prior to
beginning a topical testosterone formulation.
However, long termcontrolleddatadocumenting the
benefits and risks of TRT aremissing, and uncertainties
still surround the nature of key associations, such
as TRT and cardiovascular disease. Clinicians and
patients might ultimately decide not to use TRT, but
for those who choose treatment, available knowledge
and improved treatment options should enable them
to proceed with greater confidence that the effort will
be safe and beneficial.
Lifestyle interventions
TRT is only the pharmacologic component of TD
therapy. Positive health behaviors, such as exercise,
diet, and avoidance of smoking, are considered ameans
of preventing TD, and they correlate significantly with
higher testosterone levels over time in population-
based research.
54
In a small but compelling study
of men with TD along with newly diagnosed type
2 diabetes and metabolic syndrome, intervention
with supervised diet and exercise improved not just
testosterone levels but glucose parameters, lipid levels,
and waist circumference. For men randomly assigned
to receive both lifestyle therapy and TRT (in the
form of a gel, 50 mg/day), these improvements were
significantly greater versus lifestyle changes alone.
All of the subjects receiving lifestyle + TRT achieved
current targets for glycemic control—without the use
of antihyperglycemic medications before or during
the 52-week trial.
55
More studies of this combination
would be helpful to further define its impact, but at
present there are no arguments to be made against the
use of both lifestyle change and TRTwhen intervening
in hypogonadism.
Benefits and risks of TRT
The purpose of TRT is to alleviate hypogonadal
symptoms, but the broader goal is to give the patient
a better quality-of-life, reduce major morbidity and
disability, and “add life to years.”
43
Yet, of course there
is no evidence that this is true. Therapy is also not
recommended generally for menwith low testosterone
but without symptoms of hypogonadism. However,
accumulating evidence and clinical experience suggest
that for men with unequivocal TD, biochemical and
symptoms, therapy can achieve clear symptomatic
improvements with a low risk of side effects. Evidence
about the greater goals of TRT, particularly the impact
of therapy on cardiovascular disease and prostate
cancer, remains limited but encouraging.
Benefits
TRT is associatedwith improvements inmany domains
of sexual function, including sexual desire, sexual
activity, and sleep-related erections.
11,56-58
ED itself
may not respond as well to TRT if vascular disease is
also present, a more common finding in older men.
59
However, in hypogonadal men aged 18-80 years, the
addition of TRT to sildenafil has significantly improved
erectile function that was unresponsive to sildenafil
alone.
60
Testosterone replacement also improves bone
mineral density, chiefly in the spine and femoral neck,
especially at years 2-3.
61,62
Some experts point out that
effects on bone are moderate;
11
others say the effects are
marked enough to serve as a measure of TRT efficacy.
63
Unfortunately, studies have not been large enough to
examine the key question of whether TRT can reduce
fracture risk alongwithbonedensity improvements.
43,56,63
TABLE 4.
Biochemical definitions of hypogonadism
11,13,14,44
Society guidelines
Total testosterone
ng/mL
ng/dL
nmol/L
EAA, ISA, ISSAM
< 3.40
< 340
< 12 (mild)
EAU, ASA, ISSM
< 2.31
< 231
< 8 (severe)
ES
< 3.00
< 300
< 10.4
AACE
< 2.00
< 200
7
EAA = European Academy of Andrology; ISA = International Society of Andrology; ISSAM = International Society for the
Study of theAgingMale; EAU = EuropeanAssociation of Urology; ASA=American Society of Andrology; ISSM= International
Society for Sexual Medicine; ES = Endocrine Society; AACE = American Association of Clinical Endocrinologists
47
Testosterone deficiency: myth, facts, and controversy
