© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
physicians from several global regions concluded that
35% of testosterone-deficient men are not receiving
treatment.
31
An Anderson/Reuters internet survey
of men with TD, reported at the 2009 meeting of the
Endocrine Society, indicated that 36% of the men saw
two physicians before receiving a diagnosis, 19% saw
three physicians, and 9% saw four. What explains
these findings? Key barriers to recognition of TD
include:
Lack of consensus on the definition of TD.
Lack
of consensus may be a valid point with respect to
biochemical thresholds and ranges for defining TD,
but there is agreement that TD can be appropriately
identified through evaluation of both symptoms and
abnormal biochemistry.
Lack of confidence in diagnostic tests.
The Endocrine
Society acknowledges that, among other shortcomings,
assays for total testosterone vary over three orders
of magnitude depending on a patient’s age, gender,
and coexisting diseases. Most assays have adequate
sensitivity in men but are “relatively inaccurate,” and
the manner in which most assays are performed is
“decidedly unsatisfactory.”
32
Themost widely accepted
tests are the rather expensive testing performed by
mass spectrometry or equilibrium dialysis.
Non-use of screeners.
Although validated
questionnaires are available to assess clinical
manifestations of TD,
33
they are not widely used
in primary care offices. Most are too lengthy and
are used mainly in research. This practice gap is
one reason that men suffering from depression, for
example, end up being treatedwith psychotropic drugs
when the etiology of their depression is TD. Shorter,
more practical screeners for TD are continuing to be
developed.
34
Nonspecificity of signs and symptoms.
Clinicians and
patients alike may attribute TD symptoms to other
conditions, most commonly normal aging—a natural
decline. Yet, these symptoms, no matter how vague,
may be having a profound impact on the patient’s
quality-of-life and well-being, and should be explored
as part of overall health management.
Perception that TD is difficult to manage.
This
perception is based on the lingering but unsupported
belief that testosterone therapy increases the risk of
prostate cancer and must, at minimum, be intensively
monitoredwith prostate-specific antigen (PSA) testing.
Indeed, a 2007 survey of physicians worldwide found
that responders showed a “very powerful” fear of
inducing prostate cancer by way of testosterone
therapy; 68% of respondents (especially those based
in Europe) associated therapy with greater risks than
benefits.
31
While it is true that the long term outcomes
of testosterone therapy are not well defined, therapy
has never been proved to cause the development or
progression of prostate cancer. To the contrary, some
findings suggest that TD is the riskier condition with
respect to cancer. Testosterone replacement even for
men with a history of treated prostate cancer is no
longer considered unusual.
35,36
The Endocrine Society
recommends initial PSA testing and digital rectal
examination for all patients when testosterone therapy
is being considered. If all factors are normal, these
tests should be repeated at 3 months, but thereafter
they need be repeated only in accord with standard
screening recommendations.
11
While these remain a
source of controversy, we usually screen at baseline,
3-6 months, and thereafter, annually, if PSA is stable.
Primary care evaluation
Most patients who are experiencing TDwant to know
why they have the condition and where it originated.
Although it is sometimes possible for the clinician to
arrive at a definitive etiology of individual cases, more
often the cause is multifactorial and complex.
37,38
The
possible sites of origin are the testes, where testosterone
is produced; and the brain, where the production
process is regulated via the hypothalamic-pituitary-
gonadal (HPG) axis. These two sites are the basis
of a general classification scheme for TD in which
hypogonadism is considered primary if it is testicular
in origin and secondary if it results fromhypothalamic
or pituitary dysfunction, Table 3.
39,40
Each type of
hypogonadism can result from an inherited trait or
be acquired in life, and each type can occur in men
of any age. However, most cases of hypogonadism
in men aged 50-70 years are a mixed form, involving
testicular failure as well as central defects of the HPG
axis.
39,40
This form corresponds to what is often called
adult-onset or late-onset hypogonadism, or LOH.
38
Relatively few cases of TD are primary; those
that occur are usually congenital in origin, such as
Klinefelter’s syndrome, the most common primary
form.
39
Other primary causes include mumps
orchitis, cryptorchidism, chemotherapy/radiation
therapy, and testicular trauma.
40
Causes of secondary
hypogonadism include hypothalamic or pituitary
lesions, cranial trauma, hyperprolactinemia, and
Kallmann syndrome (genetic). Aging, acute illnesses,
certain medications, and chronic illnesses including
alcoholism, diabetes, cardiovascular disease, and
sickle cell disease are believed to play causative roles
in mixed hypogonadism.
40,41
Although all forms of hypogonadism involve TD,
theydiffer somewhat in their characteristicgonadotropin
43
Testosterone deficiency: myth, facts, and controversy
