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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
in comorbidities, baseline demographic characteristics,
or medication use compared to patients in other trials
who hadmore severe ED. This suggests that evenmild
ED is a risk factor for diseases associated with ED.
19
These studies highlight the importance of assessing
patients for potential ED as part of their routine
clinical evaluation, because ED can be an indicator of
other potential comorbidities such as cardiovascular
disease, high cholesterol, or diabetes. Physicians may
consider referringmenwith evenmild ED for a cardiac
evaluation to rule out underlying cardiovascular
disease.
Hypogonadism
In addition to providing information about ED, the
Massachusetts Male Aging Study also provided
information about changes in testosterone that occur
with aging. The key findings were that free testosterone
declined by 2.8%per year, total testosterone declined by
1.6%per year, albumin-bound testosterone declined by
2.5% per year, and testosterone bound by sex hormone
binding globulin (SHBG) increased by 1.3% per year.
2
A healthy man produces about 5 mg to 7 mg
testosterone each day. Only 1% to 2% of testosterone is
free or “bioavailable” to tissues, however, and the rest
is bound to plasma proteins. Around 35% is bound to
albumin and around 65% is bound to SHBG.
2
In women, menopause, occurs around age 50 and
has a fairly abrupt onset with the complete cessation
of reproductive hormone production. All women
undergo menopause, and it is manifested clinically.
In men, testosterone deficiency syndrome can begin
around age 40, and it occurs as a gradual decrease
in testosterone production, where blood levels of
testosterone drop but never fall to zero. Not all men
have a decrease in testosterone, and not all men are
affected in the same way by a decrease in testosterone.
In some men, testosterone levels may drop from the
upper end to the middle or lower end of the normal
range, which can still result in noticeable symptoms.
20
Testosterone is vital for normal functioning
throughout a man’s life. Signs and symptoms of
testosterone deficiency include diminished levels of
energy, sense of vitality, or sense of well-being, or
increased fatigue, aswell as depression, reducedmuscle
mass and strength, reduced bone density, anemia,
frailty, and sexual symptoms such as diminished libido,
ED, difficulty achieving orgasm, diminished intensity
of the experience of orgasm, and diminished penile
sensation.
3
Testosterone deficiency is a common comorbidity in
manymedical conditions including diabetes, metabolic
syndrome, depression, and obesity. Testosterone
production and metabolism are affected by tumors
or other disease in the sellar region, HIV-associated
weight loss, end-stage renal disease and maintenance
hemodialysis, moderate to severe chronic obstructive
lung disease, radiation to the sellar region, and certain
medications.
21
It is important for physicians to look
for low testosterone in patients who have these
comorbidities or are receiving these treatments.
The Androgen Deficiency in Aging Men (ADAM)
questionnaire, developed by John Morley, MD, at
the Saint Louis University School of Medicine, in
Missouri, is a useful, validated questionnaire, when
investigating whether a patient may have biochemical
hypogonadism.
20
If the patients’ history and clinical
assessment (including the ADAM questionnaire)
suggest potential hypogonadism, the subsequent
recommended diagnostic evaluation includes
laboratory tests to determine total testosterone and
other markers.
21
Studies have shown that men with diabetes have
lower total testosterone levels that also correlate with
increased SHBG levels.
22-24
Loughlin and colleagues examined the relationship
between low testosterone, metabolic syndrome, and
mortality in a prospective study of 794 men aged 50 to
90 years.
25
They reported that close to one-third of the
men (29%) had low testosterone (< 8.7 nmol/L). Men
with low testosterone had a 1.33-fold greater risk of
death (confidence interval [CI] 1.10-1.62). Testosterone
levels were inversely related to interleukin-6 (IL-6)
and high-sensitivity C-reactive protein (hsCRP) levels.
Men who had metabolic syndrome had a 3.05-fold
increased risk of low testosterone (CI 1.88-4.95).
In men, metabolic syndrome is strongly associated
with low testosterone levels and significant health
risks. Total and bioavailable testosterone are inversely
associated with body mass index (BMI).
24
Testosterone replacement therapy
Many studies have confirmed the association between
hypogonadism and other morbidities such as
depression, osteoporosis, decreased muscle strength,
and lipid abnormalities. Testosterone replacement
therapy is expected to benefit patients by affecting
these comorbidities.
Potential benefits of testosterone replacement
therapy include increases in overall health and
survival,
25
strength,
26
sexual desire,
27
energy,
28
emotional
well-being,
28-30
cognition,
29
bone mineral density,
31
glycemic control,
32
cardiovascular health,
33-35
and
erectile function,
36,37
improvement in some metabolic
5
Erectile dysfunction and hypogonadism (low testosterone)