© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
of Ageing Male (ISSAM), European Association of
Urology (EAU), European Academy of Andrology
(EAA), and American Society of Andrology (ASA)
also define TD as a clinical and biochemical syndrome
associated with advancing age and characterized by
symptoms and a deficiency in serum testosterone
levels.
13
Although there is general agreement among
guidelines on the common symptoms of TD, Table 1,
consensus is lacking regarding biochemical parameters
to confirm the diagnosis.
The Endocrine Society suggests that symptoms
of TD correspond to the lower limit of normal for
young men, or < 300 ng/dL, and that this may
be an appropriate defining point for TD.
11,12
The
American Association of Clinical Endocrinologists
(AACE) proposes a TT level of 200 ng/dL as lower
limit of normal.
14
The ISA/ISSAM/EAU/EAA/ASA
recommendations propose 230 ng/dL as the point
below which patients will usually benefit from
testosterone repletion,
13
and consider those men with
levels above 230 ng/dL but less than 350 ng/dL as
deserving a trial of TRT if they include symptoms.
Consensus is also lacking on parameters for free
testosterone, which guidelines say should bemeasured
when total testosterone is nondiagnostic.
Prevalence of testosterone deficiency
While key studies have arrived at different numerical
conclusions, they present an overall picture of
TD increasing with age and in association with
comorbidities including diabetes and metabolic
syndrome.
The Hypogonadism in Males (HIM) study
15
is an
example of a biochemical prevalence study. This was
a cross-sectional study of 2162 men aged 45 years and
older who had visited a primary care office for any
reason, not necessarily for TD-associated complaints,
in 2003 and 2004. Thirty-nine percent of the men
were defined as being hypogonadal based on total
testosterone of < 300 ng/dL; for every 10 year increase
in age, the risk of hypogonadism increased by 17%,
Figure 1. By extrapolating to national census data,
the HIM authors estimated that 13.8 million men
(39%) aged 45 and above who visit a primary care
physician in the United States might have biochemical
testosterone deficiency, which may or may not be
associated with clinical symptoms.
15
Prevalence was much lower in the Massachusetts
Male Aging Study (MMAS), which assessed both TD
symptoms and biochemistry in a population-based
randomsample of 40 to-70 year-oldmen.
16
In this study,
testosterone deficiency was defined by the presence of
at least three signs or symptoms of TD plus a TT level
of < 200 ng/dL; or signs/symptoms plus TT of 200
ng/dL-400 ng/dL plus free testosterone < 8.91 ng/dL.
The prevalence of TD was estimated to be between 6%
and 12%.
17
An analysis of Boston Area Community
Health (BACH) data (2000 to 2005) used a somewhat
stricter definition of symptomatic TD and estimated
its prevalence at 5.6% among men aged 30 to 79 years
and furthermore noted that 87% were symptomatic
and untreated.
18
The European Male Aging Study (EMAS) took
a uniquely stringent approach to defining TD in a
random sample of 3369 men aged 40 to 79 years.
19
The
list of qualifying TD symptoms was whittled down
based on the strength of each symptom’s association
with low levels of total testosterone (< 317 ng/dL) and
free testosterone (< 6.34 ng/dL). The three symptoms
that made the final cut were sexual: poor morning
erection, low sexual desire, and erectile dysfunction
(ED). Defined by these symptoms and biochemical
evidence, the prevalence of hypogonadism was
estimated at 2.1% overall,
19
increasing from as little
as 0.1% in men aged 40 to 49 to 5% in men aged 70 to
79. Prevalence also rose in line with increasing body
mass index and increasing number of comorbidities.
Wu (EMAS) as in the HIM study noted higher
TABLE 1.
Symptoms and signs suggestive of
testosterone deficiency in men
11,13,14
More specific signs and symptoms
Reduced libido
Erectile dysfunction
Osteoporosis or low bone mineral density
Decreased spontaneous erection
Reduced intensity of orgasm and genital sensation
Oligospermia or azoospermia
Very small or shrinking testes
Hot flushes, sweats
Breast discomfort, gynecomastia
Loss of pubic and axillary hair, reduced shaving
Less specific signs and symptoms
Decreased energy or vitality; increased fatigue
Depressed mood
Reduced muscle mass and strength
Poor concentration and memory
Sleep disturbance; increased sleepiness
Mild anemia
Increased body fat, body mass index
Diminished physical or work performance
40
Miner ET AL.
