surprising given that studies with both T
11
and FT
4,12
have
failed to demonstrate an association between serum levels
and symptoms. These non
f
ndings suggest that there may be
another mechanism in
fl
uencing sexual symptoms outside of T
and bioavailable testosterone levels which may include fac-
tors such as androgen receptor
e
binding af
f
nity and strength
of downstream response. Despite being validated, the ques-
tionnaires currently used in the diagnosis of hypogonadism
such as Massachusetts Male Aging Study (MMAS), ADAM,
and New England Research Institutes (NERI) have poor
speci
f
city for the diagnosis of low testosterone.
13
Our study has both strengths and limitations. We had a
relatively small sample size because we restricted our
analysis of FT to men who had
“
near-normal
”
testos-
terone levels, that is, 250-350 ng/dL. We restricted our
sample size to follow recommendations suggested by the
Endocrine Society guidelines.
2
The guidelines suggest
evaluating FT in men with equivocal T. We also included
only men who had at least 2 separate serum hormone
assessments as suggested by the guidelines, who had not
received testosterone therapy in the last 6 months, and
who presented to the men
’
s health clinic with the chief
complaint of
“
low testosterone
”
or
“
symptoms of hypo-
gonadism.
”
We did not evaluate factors such as obesity,
comorbidities, or medications that could have in
fl
uenced
T and FT levels.
In summary, we found that only T and SHBG are
positively associated with declining FT levels in men with
near-normal T levels. There is neither a clear-cut threshold
of FT nor a cluster of symptoms that identi
f
es men with
low FT levels. The true value of FT testing and evaluation
remains to be identi
f
ed in larger controlled studies.
References
1.
Moreno SA, Shyam A, Morgentaler A. Comparison of free testos-
terone results by analog radioimmunoassay and calculated free
testosterone in an ambulatory clinical population.
J Sex Med
. 2010;
7:1948-1953
.
2.
Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in
men with androgen de
f
ciency syndromes: an Endocrine Society
clinical practice guideline.
J Clin Endocrinol Metab
. 2010;95:2536-
2559
.
3.
Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of
simple methods for the estimation of free testosterone in serum.
J Clin Endocrinol Metab
. 1999;84:3666-3672
.
Table 2.
Comparison of characteristics between men with low and normal free testosterone
Patient Characteristics
FT
<
6.5 pg/mL
FT
>
6.5 pg/mL
P
Value
n
116
115
—
Age
51.08 (38.84-60.71)
37.76 (33.22-48.22)
<
.001
Total testosterone (ng/dL)
295.5 (264.25-322.25)
307 (287.5-327)
.026
Free testosterone
5.27 (4.89-6.01)
7.395 (6.72-8.21)
<
.001
Estradiol (ng/dL)
2 (2-2.5)
2 (2-3)
.674
SHBG (nmol/L)
36 (30-44)
21 (18-26)
<
.001
ADAM
32.5 (29-38)
31 (28.75-36)
.088
qADAM
4 (1-6)
4 (2-7)
.289
FT, free testosterone; Other abbreviations as in
Table 1
.
Table 3.
Univariate and multivariable analysis of hypogonadal symptoms predicting a free testosterone (analyzed as a
continuous variable)
Hypogonadal Symptoms
Beta
Standard Error
95% Con
f
dence Interval
P
Value
Univariate analysis
Age
±
0.46
0.2789
±
0.057 to
±
0.034
<
.001
Do you have decreased libido?
0.181
0.1815
±
0.175 to 0.537
.318
Do you have a lack of energy?
0.273
0.1816
±
0.083 to 0.629
.132
Do you have a decrease in strength or endurance?
0.232
0.1753
±
0.112 to 0.575
.186
Have you noticed a decreased
“
enjoyment in life
”
?
0.427
0.1801
0.074 to 0.780
.018
Are you sad and/or grumpy?
0.617
0.1794
0.265 to 0.968
.001
Are your erections less strong?
0.212
0.1822
±
0.145 to 0.569
.245
Has there been a recent deterioration in your
work performance?
0.772
0.2007
0.378 to 1.165
<
.001
Are you falling asleep after dinner?
0.246
0.1786
±
0.103 to 0.596
.167
Have you noticed a recent deterioration in your
ability to play sports?
0.092
0.1790
±
0.259 to 0.443
.607
Have you lost height?
±
0.480
0.2679
±
1.009 to 0.048
.075
Multivariable analysis
Age
±
0.040
0.0071
±
0.053 to
±
0.026
<
.001
Have you noticed a decreased
“
enjoyment in life
”
?
0.293
0.2106
±
0.119 to 0.706
.163
Are you sad and/or grumpy?
0.356
0.2137
0.775 to 2.782
.095
Has there been a deterioration in your
work performance?
0.167
0.2447
±
0.312 to 0.467
.494
Only factors that were statistically signi
f
cant (
P
<
.05) on univariate analysis were included in the multivariable analysis.
Values in bold are statistically signi
f
cant (
P
<
.05).
UROLOGY 86 (2), 2015
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