The Relationship Between Anogenital Distance and Reproductive

Hormone Levels in Adult Men

Michael L. Eisenberg,* Tina K. Jensen, R. Chanc Walters, Niels E. Skakkebaek

and Larry I. Lipshultz†

From the Department of Urology, Stanford University School of Medicine, Palo Alto, California (MLE), Department of Environmental

Medicine, Institute of Public Health, University of Southern Denmark, Winsloewsparken, Odense (TKJ), and University Department of

Growth and Reproduction, Rigshospitalet, Copenhagen (NES), Denmark, and Division of Male Reproductive Medicine and Surgery,

Scott Department of Urology, Baylor College of Medicine, Houston, Texas (RCW, LIL)

Abbreviations

and Acronyms

AGD

anogenital distance

FSH

follicle-stimulating

hormone

luteinizing hormone

penile length

Submitted for publication June 3, 2011.

Study received institutional review board ap-

proval.

* Correspondence:

Department of Urology,

Stanford University School of Medicine, 300 Pasteur

Drive, Palo Alto, California 94305 (telephone: 650-

723-4537; FAX: 650-498-5346; e-mail:

eisenberg@

stanford.edu

† Financial interest and/or other relationship

with Allergan Pharmaceuticals, Auxilium Pharma-

ceuticals, AMS, Pﬁzer and Repros Therapeutics.

Purpose:

Anogenital distance is a marker for endocrine disruption in animal

studies in which decreased distance has been associated with testicular dysfunc-

tion. In this study we investigated whether anogenital distance was associated

with reproductive hormone levels in adult men.

Materials and Methods:

A total of 116 men (mean age 36.1

8.0 years) were

evaluated at an andrology clinic in Houston. Anogenital distance (the distance

from the posterior aspect of the scrotum to the anal verge) and penile length were

measured using digital calipers. Testis size was estimated by physical examina-

tion. Linear regression was used to determine correlations between genital mea-

surements and hormone levels.

Results:

Anogenital distance (r

0.20, p

0.03) and penile length (r

0.20,

0.03) were signiﬁcantly associated with serum testosterone levels while total

testis size was not (r

0.17, p

0.07). No relationship between genital length

and luteinizing hormone, follicle-stimulating hormone or estradiol was identiﬁed.

After adjusting for age the serum testosterone increased by 20.1 ng/dl (95% CI

1.8, 38.4; p

0.03) for each 1 cm increase in anogenital distance. On multivari-

able models no statistically signiﬁcant relationship existed between penile length

and testosterone levels. Moreover men with hypogonadal testosterone levels (less

than 300 ng/dl) had a signiﬁcantly shorter anogenital distance compared to men

with higher testosterone levels (31.6 vs 37.3 mm, p

0.02).

Conclusions:

Anogenital distance may provide a novel metric to assess testicular

function in men. Assuming that anogenital distance at birth predicts adult anogeni-

tal distance, our ﬁndings suggest a fetal origin for adult testicular function.

Key Words:

testosterone, hormones, genitalia, perineum

the last half century there has been

a reported decline in semen quality

and serum testosterone levels with an

increased rate in male genital abnor-

malities and testis cancers.

1–4

While

the phenomenon and etiology are un-

certain, several investigative groups

postulate an environmental factor which

disrupts normal endocrine signaling

leading to abnormal androgen action

and altered genital development.

Dur-

ing sexual development the immature

genital precursors migrate ventrally

via an androgen mediated pathway.

marker for genital development, the

AGD, has been examined in animals

and humans.

6–9

A sexually dimorphic measure, AGD

was initially used to sex animals.

6,10,11

More recently human studies have

594

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0022-5347/12/1872-0594/0

Vol. 187, 594-598, February 2012

THE JOURNAL OF UROLOGY

Printed in U.S.A.

MERICAN

ROLOGICAL

SSOCIATION

DUCATION AND

ESEARCH

DOI:10.1016/j.juro.2011.10.041