© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
70 to 88.
25
Among men aged 50 to 91 years who were
followed for 20 years in the Rancho Bernardo Study,
testosterone levels were inversely related to weight,
body mass index, blood pressure, fasting plasma
glucose, and serum insulin. However relevant these
cofactors may have been to mortality, the men with
total testosterone below the 25
th
percentile had a 40%
higher risk of death independent of obesity, lifestyle
choices (eg, exercise, smoking), and even age.
26
In
another recent study of elderly men (69 to 80 years),
low testosterone and estradiol increased the risk of
death over a 5 year period.
27
The subject of chronic opiate use and its association
with TD has not been well examined, although there
is a documented increase in both therapeutic and
nonmedical use of opioids in the last 10 years.
21
In that time span, primary care clinicians have
become increasingly familiar with men presenting
with symptoms of TD and a history of long term
use of long-acting narcotics such as oxycodone and
morphine. Chronic pain should accordingly be
considered fairly high on the list of TD comorbidities.
The mechanism of any association with TD is unclear,
although suppression of hypothalamic function may
be involved.
Understanding symptoms
Symptoms of TD are essential to the diagnosis even
though they are individually nonspecific and may
be affected by the patient’s age, comorbid illnesses,
duration of TD, previous testosterone therapy, and
other factors. The symptoms of TD itemized in clinical
practice guidelines are shown in Table 1.
11,13
According
to the guidelines, any of these symptoms, even those
considered “less specific,” should raise suspicion of
TD and prompt the clinician to measure testosterone
levels.
Sexual symptoms are appropriately at the top of
the list of “more specific” TD symptoms. Indeed, loss
of libido is sometimes considered the hallmark of TD.
Primary care clinicians might argue that fatigue is
the most common presenting symptom, but the two
problems, fatigue and low libido, often go hand in
hand. What is true is that most patients with TD come
to the attention of physicians because of the presenting
problem of ED, a condition with implications even
beyond the obvious quality-of-life issues and well-
known to be a harbinger of cardiovascular disease.
Evidence linking ED with cardiovascular disease
is not new. In 2005, a report based on data from
the Prostate Cancer Prevention Trial described ED
as a strong predictor of cardiovascular events in
men 55 and up, and the report authors encouraged
clinicians to investigate cardiovascular disease in men
this age if ED is present.
28
Testosterone deficiency,
meanwhile, is associated with both ED and increased
cardiovascular risk.
11,17,20
Yet, in guidelines on hormonal
testing in evaluation of ED, the American College of
Physicians takes no position for or against testosterone
measurement.
29
Many expertswould disagreewith this
stance and instead recommend testing of testosterone
as a routine and indispensable part of the ED work up.
Barriers to recognition of TD/areas of
uncertainty
Judging by prescriptions for testosterone therapy,
diagnoses of TD are increasing: between 1999 and
2004, prescriptions for the most popular forms of
testosterone replacement increased by approximately
200%, most notably among men younger than age
65 but also in older men.
30
Nevertheless, many men
with TD symptoms go unrecognized or receive a
diagnosis and treatment only after multiple visits to
clinicians. Astudy of a random sample of community-
based men aged 30 to 79 years found that of those
who met the criteria for TD, only 12.2% were being
treated despite access to healthcare.
18
A survey of
TABLE 2.
Risks and comorbid illnesses associated
with testosterone deficiency
2,11,15,20,24,25,27
Metabolic syndrome
Obesity
Hyperlipidemia
Hypertension
Elevated fasting plasma glucose and serum
insulin
Elevated C-reactive protein
Diabetes mellitus (type 1 or 2)
Cardiovascular disease (including aortic atherosclerosis)
Chronic obstructive lung disease
Inflammatory arthritis
Low trauma fracture
End-stage renal disease
HIV-related weight loss
Hemochromatosis
Sellar mass, radiation to the sellar region, or other
diseases of the sellar region
Chronic pain syndrome and treatment with opioids
Treatment with glucocorticoids
Radical prostatectomy
42
Miner ET AL.
