Anogenital distance as a measure of human male fertility

Abstract

Purpose In humans, recent studies have correlated anogenital distance (AGD) in adult men to testicular function. While studies of a group of men suggest an association, the utility of AGD in an infertility evaluation remains uncertain. We sought to determine the utility of AGD to predict male fertility. Methods Between 2010 and 2011, men were recruited at a urology clinic to participate. AGD was measured using digital calipers in men being evaluated at a urology clinic. ANOVA and ROC analyses were used to determine correlations between AGD, fatherhood status, and semen parameters. Results In all, 473 men were included in the analysis with a mean age of 43±13 years. Anogenital distance was significantly longer in men with higher sperm concentration, total sperm count, and total motile sperm count. In order to evaluate the discriminating ability of AGD, ROC curves were created comparing AGD and total testis volume. The area under the curve (AUC) was significantly larger for total testis volume compared to AGD when evaluating fertility (0.71 vs 0.63, p= 0.02). Similarly, there was a trend towards a higher AUC for testis volume compared to AGD for sperm concentration and total sperm count. Stratification of men with long/short AGD and large/small testes also did not improve the predictive value of AGD. Conclusions While AGD is associated with sperm production on a population level, at the individual level the distinction based AGD alone cannot accurately estimate the efficiency of spermatogenesis.

Anogenital distance and reproductive outcomes in 9‐ to 11‐year‐old boys: the INMA‐Granada cohort study

“…In the present study, AGD measurements (mean = 38 mm, 25–75th percentile = 30–45 mm) were at the lower end of the range (38–51 mm) described for young and middle‐aged men (≥18 years old) in the USA, Spain, and China (Eisenberg et al ., , ; Mendiola et al ., , ; Eisenberg & Lipshultz, ; Parra et al ., ; Zhou et al ., ). Reports on AGD length in male newborns and children under 3 years of age have ranged from 20 to 37 mm (Salazar‐Martinez et al ., ; Swan et al ., ; Thankamony et al ., ; Jensen et al ., ).…”

“…As a marker of early gonadal development disruption, AGD has been examined in relation to adverse reproductive outcomes in adult men. Thus, several studies in groups of volunteers or men attending andrology clinics have published evidence linking shorter AGD with worse sperm quality (Mendiola et al ., , ; Eisenberg & Lipshultz, ), reduced fertility (Eisenberg et al ., ), azoospermia (Eisenberg et al ., 2012b), and lower testosterone and estradiol levels (Eisenberg et al ., 2012a; Zhou et al ., ). In adults, a shorter AGD has been also related to the risk of prostate cancer (Castaño‐Vinyals et al ., ), while in male human fetuses, newborns, and infants, it has been associated with hypospadias, cryptorchidism, micropenis, and reduced thyroid hormone levels (Hsieh et al ., , ; Jain & Singal, ; Thankamony et al ., ; Liu et al ., ; Gilboa et al ., ).…”

Experimentally induced testicular dysgenesis syndrome originates in the masculinization programming window

“…As there is already a substantial body of similar association data in human males (Table 1), it is reasonable to propose that an MPW exists in humans, so that studies to identify potential causes of TDS disorders should focus on the presumptive MPW (~8-14 weeks' gestation). While such studies have several inherent limitations, the measurement of AGD in newborn offspring, as an indicator of androgen exposure within the presumptive MPW, will play an important role, even if interindividual variation may restrict its usefulness to population-based studies (11,25,36).…”

“…Hence, AGD could be measured at any postnatal age in rats and used to retrospectively decipher the level of fetal androgen exposure during the MPW (11,21). In human males, AGD shows similar male-female differences as in rats (11,(24)(25)(26), and lower AGD has been related to the occurrence of TDS disorders evident at birth (27)(28)(29)(30)(31)(32)(33) and, in a majority of studies, to lower sperm counts (34)(35)(36)(37) and hormone levels (38,39) in adult men, similar to rats (reviewed in ref. 11).…”

Morphometric variables of offspring of <i>Quassia amara</i> treated male rats

“…Moreover, human studies in infants have also established that boys have longer AGD than girls (4,5). It is a marker for endocrine disruption in animal studies and may be shorter in infant males with genital anomalies (6). Quassia amara is a 6-8 meters tall tree native to Suriname, Brazil, in South America and is naturally distributed in several tropical countries.…”