Discussion

The current study demonstrated that men with nonob-

structive azoospermia have a shorter AGD than do men

with obstructive azoospermia. Moreover, as a single mea-

sure, an AGD cutoff of 30 mm displayed a 91% speciFc-

ity for men with NOA. The relationship persisted even

after adjustment for anthropomorphic and demographic

variables. However, men with severe oligospermia seem to

have a shorter AGD compared to men with NOA.

During sexual development the immature genital pre-

cursors migrate ventrally via an androgen mediated path-

way (Larson, 1997). The anogenital distance has been

used to sex animals, because males have longer lengths

than females (Marois, 1968; Greenham & Greenham,

1977; Hsieh

et al.

, 2008). Moreover, human studies in

infants have established that boys have longer perineal

lengths than girls (Salazar-Martinez

et al.

, 2004; Torres-

Sanchez

et al.

, 2008). Hsieh

et al.

demonstrated shorter

anogenital distances in boys with genital anomalies (i.e.

hypospadias and cryptorchidism), establishing a link

between normal genital development and perineal length

in humans (Hsieh

et al.

, 2008). Recent data has demon-

strated that AGD is also related to fatherhood, fertility

and adult sperm production (Eisenberg

et al.

, 2011;

Mendiola

et al.

, 2011). To our knowledge, the current

report represents the Frst demonstration of the utility of

assessing AGD in clinical practice to aid patient care.

While testicular size is an excellent predictor of the eti-

ology of azoospermia (a fact demonstrated in the current

report), men with azoospermia with a normal genital

examination and a normal volume ejaculate are often

offered testicular biopsy with the option for testicular

sperm extraction or genital reconstruction. Other investi-

gators have reported using testicular size coupled with

±SH or testicular MRI to assist with the diagnosis of OA

vs. NOA (Schoor

et al.

, 2002; Aaronson

et al.

, 2010).

While the current report was not powered to compare

available tests, it does support the value of AGD to assist

in determining the etiology of azoospermia. While testic-

ular size does appear to be a better discriminant to deter-

mine the etiology of azoospermia, the current data

suggests that AGD may provide the urologist with addi-

tional information for patient counseling regarding the

etiology of azoospermia in equivocal cases. However, it is

important to note that as the AGD increases, its ability to

discriminate OA from NOA diminishes. Indeed, at

35 mm, the speciFcity to identify NOA men is only 71%

compared to 91% at 30 mm.

It is interesting to note that there appears to be a

J shaped relationship between AGD and TMC whereby

men with severe oligospermia have the shortest AGD.

The pathophysiology of NOA is likely multifactorial and

complex

with

androgen

fetal

insults

likely

accounting for a fraction of cases. Indeed, current data

demonstrate that genetic mutations in meiosis or germ

cell development comprise some portion of the NOA

phenotype which may not re²ect in utero androgen sig-

naling (Oates, 2008). Among the patients studied, how-

ever, those with genetic abnormalities (i.e. abnormal

karyotypes or Y chromosome microdeletions) had the

Table 4

Anogenital distances stratifed by total motile sperm count

(TMC) quintiles. The TMC range For each quintile is listed

TMC

quintile

Total motile sperm

count (millions)

AGD (mm)

Median (95% CI)

Mean (SD)

Median (range)

0 (0,0)

32.4 (12.4)

30 (13, 56)

0.93 (0.05, 1.9)

29.0 (8.1)

29.9 (13, 44.5)

5.6 (2.1, 10)

32.9 (14.4)

28 (14, 82.8)

16.4 (11.6, 30.7)

37.6 (10.4)

36 (22.9, 55.9)

55 (31.7, 147.7)

39.2 (12.4)

39.3 (19.8, 78.6)

Figure 1

Boxplot showing the interquartile range (IQR) oF the AGD

stratifed by total motile sperm count quintiles. Median values

denoted by horizontal bar. Whiskers designate 1.5

IQR.

Table 5.

Anogenital distance and total testis sizes stratifed by OA,

NOA – normal genetics (i.e. normal karyotype and Y chromosome),

NOA – abnormal genetics (i.e. abnormal karyotype or Y chromosome)

AGD

Total testis size

Group

Mean

(SD)

Median

(95% CI)

Mean

(SD)

Median

(95% CI)

69 41.9 (11.3) 40 (28.6, 60.2) 41.7 (6.2) 44 (30, 50)

NOA

Normal genetics

23 39.0 (16.8) 34 (20.7, 62)

27.7 (7.0) 28 (16, 36)

NOA

Abnormal genetics

6 26.1 (9.4)

24 (17.9, 44)

21.7 (5.4) 21 (16, 28)

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

729