© The Canadian Journal of Urology™; 21(Supplement 2); June 2014
the presence of a microadenoma. If such an adenoma
is found, then referral is made to an endocrinologist
for the appropriate therapy with a dopamine agonist.
Therefore, in the case TD, in this algorithm the use
of serum LH is of value since the level of this hormone
indicates where the failure is located: in the testes if
the serum LH is high (primary TD), or at the level of
the hypothalamus or pituitary if the serum LH is low
or normal (secondary TD). Secondary TD necessitates
the measurement of a serum prolactin because if T
< 150 ng/dL, as it may result fromhyperprolactinemia,
a condition often associated with curable diseases like
pituitary tumor. MRI is required as above as proposed
by the Endocrine Society if T is below this threshold
[< 5.2 nmol/L; 150 ng/dL]. This was based on as single
study of 159menwith EDwho had T levels < 8 nmol/L
and non-elevated LH. Eleven potentially serious
hypothalamic or pituitary lesions were identified
(6.7%).
48
Secondary TD may also require screening
for hemochromatosis withmeasurement of transferrin
saturation and serum ferritin.
Key learning points:
There are no generally accepted lower limits of
normal TT.
There is, however, general agreement that:
• TT > 12 nmol/L(3.5 ng/mLor 350 ng/dL)
doesnot usually require substitution
• Based on the data of young hypogonadal
men,menwithTT < 8 nmol/L(2.3 ng/mLor
230 ng/dL) usually benefit fromT treatment
Between these levels:
• Measuring FT by equilibrium dialysis or
calculating it from TT and SHBG levels may
be helpful in case of TT between 8 nmol/L
and 12nmol/L. Alower limitof 225pmol/L
(65 pg/mL) is accepted by many.
• A T trial for 3-6 months may be envisaged
in those patientswho are symptomatic, while
alternative causes of the symptoms have
been excluded. Beyondthattime,Ttherapy
wouldbecontinuedonlyincaseofsubstantial
benefit
Measuring testosterone: what do the values
mean?
Different thresholds exist for treatment according to
specific guidelines and thus vary in regard to the lower
level for therapy, Table 4. Total testosterone (TT) has
been the traditional measure for use in corroboration
of hypogonadism. Testosterone levels in healthy
men follow a circadian rhythm, with levels peaking
in the morning. Accordingly, guidelines recommend
measurement of TT in a blood sample taken during
morning hours, preferably after the patient has fasted.
A positive finding should be repeated, especially if
borderline.
11,42
It is generally agreed that a TT level of > 350 ng/dL
doesnot require treatment andsuggestsnon-testosterone
sources of symptoms. Otherwise, the recommendation
is to consider treating men with “unequivocally low”
testosterone along with symptoms. Clinicians should
be aware that TT measurements do not necessarily
correspond with the patient’s clinical presentation.
Some research supports symptom-specific levels of TT
below which the prevalence of the symptom starts to
increase.
49
Other research finds no symptom-specific
thresholds but further evidence that the severity of
symptoms increases with decreasing testosterone level,
especially the severity of psychological symptoms.
50
TT represents the total of free testosterone plus
hormone bound to sex hormone-binding globulin
(SHBG) and albumin. TT levels are subject to
alterations in SHBG that occur in association with
obesity, old age, diabetes, medications, and other
confounders.
11
Measurement of free testosterone can
be of diagnostic value in cases where TT does not
correspond with the clinical picture. However, this
practice is limited by the availability of assays and,
again, a lack of consensus on threshold values. Many
clinicians who regularly see men with TD suggest
a threshold of 8 ng/dL to define hypogonadism by
calculated free testosterone. For measurement via the
analog free testosterone assay, values < 1.5 ng/dLhave
been proposed as a lower limit of normal.
51
Treatment
The goal of TRT is to safely restore testosterone to
normal physiologic levels, thereby ameliorating
symptoms associated with TD and improving
patient health and well-being. At the biochemical
level, the goal is to raise total testosterone to a range
considered normal for healthy youngmen, 300 ng/dL-
1050 ng/dL.
11,38,39,40
The Endocrine Society specifies
a mid-range goal of 400 ng/dL-700 ng/dL for
repletion. Note that these are physiologic (eugonadal)
testosterone levels, not supraphysiologic levels; there
is no basis for recommending TRT dose escalations
in pursuit of greater efficacy, and the practice may
increase the risk of treatment side effects.
52
TRT should
also achieve physiologic levels of key testosterone
46
Miner ET AL.
