© The Canadian Journal of Urology™; 19(Supplement 1); October 2012
23
Erectile dysfunction and testosterone deficiency syndrome: the “portal to men’s health”
androgens, and research is underway to try to develop
selective androgen receptor modulators (SARMs).
In men, testosterone is produced by the Leydig
cells in the testis. In the blood, only 2% of testosterone
is free, up to 40% is bound to albumin, and the rest
is bound to sex-hormone-binding globulin (SHBG).
Bioavailable testosterone (BT) is the sum of free
testosterone and albumin-bound testosterone.
29
Testosterone is metabolized into inactive products
in the liver, and, in fat tissue it can be metabolized and
converted to estradiol via aromatization. Therefore,
an obese individual may develop gynecomastia as one
of the sequelae of raising or changing the estrogen/
testosterone ratio through increased aromatization.
30
Testosterone targets the following organs and has
the following effects:
•
Skin (hair growth balding, sebum production)
•
Muscle (strength, volume, energy, reduction in
visceral fat)
•
Male sexual organs (penilegrowth, spermatogenesis,
erections, prostate growth and function)
•
Bone marrow (stimulation of stem cells)
•
Brain (libido, mood, cognition)
•
Heart (cardiovascular health)
•
Liver (protein synthesis)
•
Kidney ( stimulation of erythropoietin production)
•
Bone (strength and density)
As suggested by the many target organs for
testosterone, the clinical manifestations of TDS are
considerable.
31,32
These can include decreased libido,
decreased vitality, fatigue, mood changes, insomnia,
anemia, ejaculatory disturbance, erectile dysfunction,
hot flushes, decreasedmuscle mass, increased visceral
body fat, testicular atrophy, weakness, osteopenia/
osteoporosis, and loss of facial, axillary, and pubic hair.
Clinical disorders associated with TDS
Low levels of serum testosterone are quite common in
many clinical disorders/conditions including type 2
diabetes, metabolic syndrome, HIV-associated weight
loss, treatment with opioids, glucocorticoids or
ketoconazole, osteoporosis or low-trauma fracture at a
young age, end-stage-renal-disease and maintenance
hemodialysis, chronic obstructive pulmonary disease
(
COPD), and infertility.
33
Patients with these clinical
disorders/conditions are considered to be at high risk
for TDS and should be screened for this disorder.
34
Among men with diabetes, about 30% to 40% have
low testosterone
35
and 40% to 50% have ED.
36
Men with
higher levels of testosterone (15.6nmol/Lto21.0nmol/L)
have a 42% lower risk of developing diabetes compared
to men with normal levels of testosterone.
37
A study found that 74% of men with chronic pain
who take sustained-action oral opioids have low
levels of testosterone.
34
This opioid-induced androgen
depression (OPIAD) has a marked negative effect on
male sexual function.
A study using data from the Male Massachusetts
Aging Study,
38
found that in 17 years of follow up,
compared with men whose total serum testosterone
was 14 nmol/L to 18 nmol/L, men whose total serum
testosterone was less than 7 nmol/L had a 2-fold
higher risk of death, a 3-fold higher risk of cancer, and
a 2-fold higher risk of cardiovascular death.
39
Shores
and Matsumoto
40
used data from the Veteran’s Affairs
clinical database to assess how low testosterone is linked
with all-cause mortality. Of 858 men over age 40, 166
men (19%) had a low serum testosterone level; these
men had a mean age of 63.6. During 4.3 years of follow
up, 34.9% of men in the low-testosterone cohort died
versus 20.1% of men in the normal-testosterone cohort.
Testosterone and the prostate
Concerns about testosterone administration and its
effect on the prostate is a leading cause of reluctance
to treat patients with TDS.
In 2006, Morgentaler
41
performed a comprehensive
review of testosterone and the prostate. He found no
increase inprostate cancer in clinical trials of testosterone
supplementation in normal men or even in men at
increased risk for prostate cancer, such as those with
previouslydiagnosedhighgradeprostatic intraepithelial
neoplasia (PIN), possibly a pre-malignant lesion. He
also reported that there was no link between prostate
cancer and testosterone levels in multiple longitudinal
studies. As men aged, testosterone levels dropped, but
the incidence of prostate cancer increased. Men with
more aggressive prostate cancer had lower levels of
testosterone.
Prostate volume increases with age in normal
men but not in untreated hypogonadal men. When
hypogonadal men are treated with testosterone, their
prostate volumes may increase, but only to the size of
eugonadal men. Placebo-controlled studies showed
that the differences between men receiving TRT and
those receiving placebo were insignificant in terms
of prostate volume, PSA, and LUTS. However, the
belief that testosterone can promote the growth of an
established prostate cancer is well-established.
Diagnosing TDS
In 2010, two comprehensive publications outlining
practice guidelines for TDSwerepublished: anAmerican
