The relationship between anogenital distance and
azoospermia in adult men
Michael L. Eisenberg,* Michael Shy,
R. Chanc Walters
and Larry I. Lipshultz
*Department of Urology, Stanford University School of Medicine, Palo Alto, CA, USA and
Division of Male Reproductive Medicine and Surgery,
Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA
A sexually dimorphic measure of genital development
under hormonal inFuence, AGD was initially used to sex
animals (Marois, 1968; Greenham & Greenham, 1977;
et al.
, 2008). More recently, human studies have
also shown that boys have longer perineal lengths than
girls (Salazar-Martinez
et al.
, 2004; Torres-Sanchez
et al.
2008; Thankamony
et al.
, 2009; Sathyanarayana
et al.
2010). Investigators have also used AGD to show that
agents which disrupt androgen signaling in animal models
can lead to abnormal genital lengths and even altered
testicular function as measured by testosterone and sperm
production (±oster
et al.
, 2001; Scott
et al.
, 2008; Marti-
et al.
, 2009; Cowin
et al.
, 2010). Human
studies have also linked adult testicular function, as
assessed by sperm and testosterone production, to ano-
genital distance (Eisenberg
et al.
, 2011, 2012; Mendiola
et al.
, 2011). However, the clinical utility of such mea-
surements remains unclear.
Azoospermia is responsible for approximately 5–20%
of male infertility in the USA (Kolettis, 2002). While the
etiologies can be diverse, they generally are categorized as
obstructive or nonobstructive when treatment options are
being considered. The classi²cation usually relies on phys-
ical examination and hormone pro²le. However, the
distinction between obstructive and nonobstructive azoo-
spermia is uncertain and occasionally warrants a testicular
biopsy to con²rm a diagnosis. As measurement of ano-
genital distance may provide a noninvasive method to
assess male reproductive potential and testicular function,
we sought to determine if AGD could be used to differen-
tiate obstructive from nonobstructive azoospermia.
Materials and methods
The methods of collection and cohort assembly have been
reported previously (Eisenberg
et al.
, 2011, 2012). BrieFy,
after Institutional Review Board approval was obtained
from Baylor College of Medicine, eligible patients were
azoospermia, genitalia, humans, perineum
Michael L. Eisenberg, Department of Urology,
Stanford University School of Medicine, 300
Pasteur Drive, Stanford, CA 94305-5118,
USA. E-mail: eisenberg@stanford.edu
Received 27 December 2011; revised 5 March
2012; accepted 10 March 2012
Anogenital distance (AGD) is a marker for endocrine disruption in animal
studies in which decreased male AGD has been associated with testicular dys-
function. The objective of the study was to investigate whether anogenital dis-
tance could distinguish men with obstructive azoospermia (OA) from those
with nonobstructive azoospermia (NOA). To accomplish this, azoospermic
men were recruited and evaluated at a men’s reproductive health clinic in
Houston, TX. Anogenital distance (the distance from the posterior aspect of
the scrotum to the anal verge) and penile length (PL) were measured using
digital calipers. Testis size was estimated by physical examination. Logistic
regression was used to compare AGD lengths in men with OA and men with
NOA. A total of 69 OA men (mean age: 44.2 ³ 9.2) and 29 NOA men (mean
age: 32.8 ³ 4.8) were recruited. The NOA men possessed signi²cantly shorter
mean AGD than the men with OA (AGD: 36.3 vs. 41.9 mm,
= 0.01). An
AGD of less than 30 mm, had a 91% speci²city in accurately classifying NOA.
Moreover, after adjustment for age, race, and BMI, an AGD of less than
30 mm yielded a signi²cantly increased odds of NOA compared to OA (OR
5.6, 95% CI 1.0, 30.7). In summary, AGD may provide a novel metric for
assessing testicular function in men and in distinguishing OA from NOA.
international journal of andrology ISSN 0105-6263
International Journal of Andrology
, 2012,
, 726–730
2012 The Authors
International Journal of Andrology
2012 European Academy of Andrology