Hypogoadism: Diagnosis

From: www.nature.com

The prevalence of symptomatic late onset hypogonadism (SLOH) can be estimated from population
based studies. Numerous cross-sectional and longitudinal
studies have shown that there is an age-related
decline in androgen production in adult men [7, 8]. Studies
suggest a prevalence of SLOH varying from 2% to
70% [2, 16], with most trials reporting a prevalence rate
of 15–20%, while it is general higher in referral biased
studies [51].

Recently Araujo et al. [9] investigated the
prevalence of SLOH in men between the ages of 30 to
79 through the Boston Area Community Health (BACH)
survey. SLOH was defined as low total (< 300 ng/dL)
and free (< 5 ng/dL) testosterone and decreased libido,
ED, osteoporosis or fracture, or two or more following
symptoms: sleep disturbance, depressed mood, lethargy,
or diminished physical performance. Results of that
study showed that low testosterone and free testosterone
levels were present in 24% and 11% men respectively.

The prevalence of SLOH symptoms were: decreased libido
(12%), ED (16%), osteoporosis/fracture (1%) and
two or more of the non-specific symptoms (20%). The
prevalence of SLOH was 5.6%, independent of race, and
increased markedly with age [9].

5 Diagnosis of hypogonadism
The diagnosis of hypogonadism in men should based
on both the suggestive clinical picture and the biochemical
findings of low androgens. Initially a sexual, psychosocial
and medical history should be obtained. Following
this a focused physical examination should be
performed on all aging men. Patients with SLOH may
present with characteristic symptoms including decreased
sexual desire, impaired erections, poor sleep related
erections, reduced sexual pleasure, muscle atrophy,
and delayed or absent orgasm. Additionally, changes in
mood, diminished feelings of well being, loss of motivation,
fatigue, depression, anger, decrease in body hair,
osteoporosis due to decreased bone mineral density, an
increase in visceral fat are frequently observed in patients
with SLOH [2, 17]. Small and less firm testes are usually
consistent with hypogonadotrophic hypogonadism. Of
note, these findings need not all be present for the diagnosis
of SLOH. Furthermore, using screening questionnaires
as an adjunctive tool for the diagnosis of hypogonadism
can be helpful.

The ADAM scale is commonly
used, its specificity is very low in the aging male. The
Aging Male Scale (AMS) and ANDROTEST are also both
reliable in detecting the presence or absence of androgen
deficiency symptoms [51–53]. However, these validated
questionnaires should not be considered alternative
instruments, but a useful supplement to a detailed history
and proper physical examination [2, 17].
As mentioned, the diagnosis of SLOH in men is based
on the clinical picture and biochemical documentation of
androgen deficiency. Low testosterone level alone is not
an indication for administration of hormonal therapy.
Several laboratory ranges for androgens are not always
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Androgens and erectile dysfunction
http://www.asiaandro.com; aja@sibs.ac.cn
reliable and sometimes at best are a rough approximation
of the androgen status [2, 17]. Furthermore there is no
absolute threshold value of testosterone which exactly
defines the state of androgen deficiency. Because only
unbound testosterone can act within cells, it is possible
that TT measurements may be misleading. In normal
men, 2% of testosterone is free and 30–60% is bound to
SHBG with high affinity. In contrast the remaining
amount of testosterone is bound to albumin and other
serum proteins with a much lower affinity. Changes in
SHBG can increase or reduce the effective testosterone
milieu, which suggest that SHBG at least in part regulates
androgen function.

Therefore in patients who are
suspected for androgen deficiency, SHBG levels need to
be evaluated. On the other hand, some authorities suggest
that, determination of free testosterone levels delivers a
more reliable assessment about the androgen status of
adult men [2]. There are a number of biases inherent in
the methods used to determine free testosterone values.

Direct free testosterone measures using a testosterone
analogue assay do not provide reliable free testosterone
results. Although, equilibrium dialysis and ultracentrifugation
are reliable, they are not widely available and are
technically difficult. BT using ammonium sulphate precipitation
is generally used, reliable and less expensive [2].

The following provides a summary of biochemical
assessments for SLOH:
1) Measure serum TT between 8.00 and 11.00 a.m.
2) If testosterone levels are below the normal limit
(350 ng/dL) confirm the results with a second determination
together with measurement of LH, FSH and
prolactin. In the younger (< 40 years) men, low testosterone
levels concomitant with elevated gonadotrophins
indicates the presence of primary hypogonadism. In this
circumstance prolactin levels are needed to rule out hyperprolactinemia.
3) In patients with a total testosterone level less than
200 ng/dL with accompanying signs and symptoms of
hypogonadism, further calculation of free and/or BT is
not necessary. On the other hand free testosterone or
BT are required in men with SLOH who have a borderline
(200–400 ng/dL) testosterone value. In the first step, TT
(ng/dL), SHBG (nmol/L) and albumin (g/dL) concentrations
are measured. Calculation of the free testosterone
or BT levels can be performed with the help of the International
Society for the Study of the Aging Male (ISSAM)
Web page (www.issam.ch). Calculated values of free
testosterone less than 5 ng/dL is considered abnormal,
whereas values less than 110 ng/dL for BT suggests androgen
deficiency [2, 17].