unique symptom pro
les associated with endogenously low
serum TT and free testosterone levels.
Patients and Methods
After approval by the Institutional Review Board at Baylor
College of Medicine (Houston, TX, USA), we evaluated 352
men (aged
40 years) seen consecutively between May 2013
and March 2014. These men presented with a chief
complaint of
low testosterone
. Men using testosterone or
other androgenic anabolic steroids (AAS) either at, or
6 months prior to, the time of the survey were excluded.
We also excluded men who had presented with a primary
diagnosis of infertility, Kleinfelter
s syndrome, or secondary
hypogonadism after appropriate assessment of history and
endocrine evaluation with gonadotrophins. All men
answered the Androgen De
ciency in the Aging Male
(ADAM) questionnaire [9,10] and on the same day their
testosterone levels were measured. The ADAM
questionnaire consists of 10
questions about
symptoms, although not all of them necessarily indicate
treatable symptoms of testosterone de
ciency. All venous
blood samples were obtained under standardised conditions
before 10:00 h from fasting patients. Serum or plasma were
separated at 800
. Serum TT and sex hormone binding
globulin measurements were done using the
radioimmunoassay Beckman Access II platform (Beckman
Coulter, Fullerton, CA, USA). TT levels were
tted on a
scatter plot to determine in
ection points and threshold
levels. Data was analysed using Microsoft Excel (Microsoft,
Redmond, WA, USA) and
(SPSS Inc., Chicago, IL,
USA). Chi-squared tests were used to compare percentages
and the Student
-test was used to compare means. The
Q test was used to verify that the variables were
continuously distributed. Univariate and multivariable
analysis was performed for age and the 10 symptoms
ed on the ADAM questionnaire. Variables that were
statistically signi
cant on the univariate analysis were
included in the multivariable analysis. All values are
reported as the mean (
) and
-tests were used to evaluate
differences in means between groups. A
0.05 was
considered to indicate statistical signi
Of the 352 men aged
40 years, 210 men had a TT level of
300 ng/dL; 67 men had levels of 300
400 ng/dL; and 75
men had levels of
400 ng/dL. The mean (
) age of the 352
men was 33.2 (4.2) years, and the mean (
; range) TT level
was 308 (170; 0.86
1537) ng/dL. Of the 10 hypogonadal
symptoms, the probability of having
ve symptoms decreased
0.05) in men with testosterone levels of
400 ng/dL
(Table 1 and Fig. 1). These
ve symptoms included two
psychological (
decreased energy
feeling sad
), and three
physical (
decreased strength and endurance
ability to play sports
, and
deterioration in work
). The probabilities of having the 10
hypogonadal symptoms that are part of the ADAM
questionnaire, were similar in men with TT levels of
300 ng/dL and men whose levels were between 300 and
400 ng/dL (Fig. 1). On a univariate analysis, the presence of
the same
ve symptoms predicted a testosterone level of
400 ng/dL. On multivariable analysis, only
lack of energy
predicted a testosterone level of
400 ng/dL. Of note, sexual
symptoms (libido and erectile function) commonly thought to
be associated with low testosterone did not identify men with
testosterone levels of
400 ng/dL. In addition, none of the 10
symptoms evaluated predicted a testosterone level of
300 ng/dL.
Hypogonadism is caused by insuf
cient concentrations of
testosterone in the blood, resulting in symptoms of androgen
ciency. The reference range for most assays of TT is 300
800 ng/dL [11,12], meaning that only 2.5% of healthy men
have concentrations of
300 ng/dL. A clinical threshold of
300 ng/dL is often cited in the literature as the biochemical
nition of hypogonadism [2]. One argument for using
300 ng/dL as the threshold for diagnosing male
hypogonadism is that there is a functional correlation with
erectile dysfunction (ED). This relationship was determined
in a study of 162 elderly (mean age 64.1 years) men with ED
(mean duration 45.6 months), where a Korean group
reported that hypogonadism (serum TT level of
300 ng/dL)
was among the strongest independent predictors of a poor
response to sildena
100 mg for 8 weeks [13]. The
threshold TT level below which signs and symptoms of
androgen de
ciency occur and testosterone replacement is
cial is not known and varies among individuals
depending on age and comorbid conditions, and among
affected target organs. Therefore, there is no absolute value of
the TT level below which clinical androgen de
ciency or
hypogonadism can be con
rmed in all patients, especially in
young men. Consequently, we evaluated the association
between hypogonadal symptoms and serum TT levels in men
who came to our outpatient men
s health clinic with a chief
complaint of
low testosterone
We identi
ed a serum TT level threshold of 400 ng/dL by
evaluating probabilities of the different hypogonadal
symptoms across various TT levels. Most previous studies
have identi
ed an association of low testosterone with sexual
symptoms, such as poor erectile function [7,14,15] and low
libido [16]. However, in our present study we found that
physical and psychological symptoms were most often closely
associated with testosterone levels of
400 ng/dL.
Interestingly, only
lack of energy
remained statistically
cant on a multivariable analysis. None of the sexual
2014 The Authors
BJU International
2014 BJU International
Hypogonadal symptoms in young men with TT
400 ng/dL