ORIGINAL ARTICLE

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

Introduction

A sexually dimorphic measure of genital development

under hormonal inFuence, AGD was initially used to sex

animals (Marois, 1968; Greenham & Greenham, 1977;

Hsieh

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-

no-Andrade

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

Keywords:

azoospermia, genitalia, humans, perineum

Correspondence:

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

doi:10.1111/j.1365-2605.2012.01275.x

Summary

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

726

International Journal of Andrology

2012 European Academy of Andrology