recruited from August 2010 through November 2010
from a urology clinic specializing in reproductive medi-
cine. Men with a history of infertility, sexual dysfunction,
hypogonadism, fecundity anxiety, or vasectomy and age
18 or older were eligible. Men with a history of orchiec-
tomy, testicular torsion, prior malignancy, prior testoster-
one use, or prior chemotherapy exposure were excluded.
Within the cohort of men who had anogenital distance
measured, we searched for men who were also azoosper-
mic deFned as an absence of sperm in the ejaculate. The
distinction between OA and NOA was made based on
history (e.g. previous vasectomy), physical examination
(e.g. testicular size), laboratory, and surgical Fndings (e.g.
testicular biopsy) (Schoor
et al.
, 2002). In all, 98 men
were azoospermic. Mean age was 36.1 ± 8.0. Of the
cohort, 58.6% were white, 13.8% were Hispanic, and
13.8% were African American. All men provided written
consent for participation.
Genital measurements
The methods of genital measurement have been previ-
ously described. Brie²y, in the supine, frog-legged posi-
tion with the legs abducted allowing the soles of the feet
to meet, the distance from the posterior aspect of the
scrotum to the anal verge was measured using a digital
caliper (Neiko USA, Model No. 01407A). It is important
to note that others have deFned the anogenital distance
(AGD) from the anus to the anterior base of the penis
and the distance from the posterior scrotum to the anus
(as was measured in this study) as the anoscrotal distance
(ASD) (Swan
et al.
, 2005; Hsieh
et al.
, 2008; Sathyanara-
et al.
, 2010). The inter-rater reliability of our mea-
surements were 0.91 for anogenital measurements at our
institution. Given the age of the patients measured, the
posterior scrotum was measured as the anterior border as
it was felt to be a more comfortable, reliable, and repro-
ducible measure.
³rom the same position, the stretched penile length
(PL) was measured from the base of the dorsal surface of
the penis to the tip of the glans. Testicular volume was
estimated at physical examination by one investigator
(LIL) in a room at approximately 25–27
C. Total testicu-
lar volume represents the sum of the right and left testes.
Hormone analysis
experienced laboratory (Laboratory for Male Reproduc-
tive Research and Testing, Baylor College of Medi-
6.9–34.7 nmol
L), LH (reference range: 6–19 mIU
and ³SH (reference range: 4–10 mIU
mL) values were
assessed using an automated, one-step competitive bind-
ing assay with the Beckman Coulter Access II Immuno-
assay system (Beckman Coulter, Inc., Brea, CA). The
assays were recalibrated everyday with controls that
spanned the normal range for all hormones.
Statistical analysis
Comparisons were made using
for most continu-
ous variables and Chi-squared for categorical variables.
Given the nonparametric distribution of the genital mea-
sures (i.e. AGD and PL), the nonparametric Mann–
-test was used for comparisons. To assess the
performance of AGD length to predict the etiology of
azoospermia, the data were stratiFed on the basis of AGD
length. Multivariable logistic regression was used to deter-
mine the relationship between AGD length and etiology
of azoospermia. Bivariable regression coefFcient between
genital measures, anthropomorphic variables (height,
weight, BMI), and the etiology of azoospermia were
determined, and relationships with a
value < 0.2 were
included in the multivariable models. Receiver operating
characteristic (ROC) curves were generated using maxi-
mum likelihood estimation to Ft a binomial ROC curve
to either continuously distributed data or ordinal category
data. All
values were two-sided. Analyses were per-
formed using Stata 10 (StataCorp LP, College Station,
In all, 98 men were azoospermic and available for analysis
– 69 men had obstructive azoospermia (OA) and 29 men
had nonobstructive azoospermia (NOA). Of the OA men,
63 had previously undergone vasectomy, 4 had CBAVD
(congenital bilateral absence of the vas deferens), and 2
had idiopathic epididymal obstruction. Mean age was
44.2 for OA men and 32.8 for NOA men. Other demo-
graphic and anthropomorphic characteristics of the OA
and NOA men were similar (Table 1). Of the NOA men,
20 had karyotypes, of which 17 were normal, and 2
showed XXY and 1 showed a Y chromosome inversion.
Seventeen NOA men had a Y chromosome microdeletion
assessment with 3 men showing abnormalities.
Men with OA had signiFcantly longer AGD than those
with NOA (mean: 41.9 vs. 36.3 mm; median 40 vs.
31.2 mm;
= 0.01). Men with OA also had signiFcantly
larger total testis size than did those with NOA (mean:
41.7 vs. 26.4 mL, median: 44 vs. 20 ml;
< 0.01). In con-
trast, there were no signiFcant differences between penile
length in men with OA and those with NOA (mean:
125.4 vs. 123.0 mm; median: 127 vs. 121 mm;
= 0.2,
Table 2).
M. L. Eisenberg
et al.
The relationship between anogenital distance and azoospermia in adult men
2012 The Authors
International Journal of Andrology
, 2012,
, 726–730
International Journal of Andrology
2012 European Academy of Andrology