Anogenital Measurements Research Articles

Associations between intrauterine exposure to polychlorinated biphenyls on neonatal ano-genital distance

Polychlorinated Biphenyls (PCBs) are widespread environmental contaminants. PCBs have endocrine disrupting properties which raises concerns regarding their effect on the developing fetus.This study aimed to examine the association between prenatal exposure to PCBs and anogenital distance (AGD) in newborns.Serum concentrations of PCB congeners -118, -138, -153 and -180 were measured in 175 pregnant women presenting to the delivery room. AGD was measured in their newborns. Regression models were used to estimate associations between maternal PCB exposure and infant anogenital measurements, controlling for possible confounding variables.Mean maternal serum concentrations were 2.95 ± 2.18 ng/g, 4.62 ± 3.54 ng/g, 7.67 ± 6.42 ng/g and 5.10 ± 3.91 ng/g for congeners -118, -138, -153 and -180, respectively. Higher maternal concentrations of PCBs were associated with reduced AGD measures in male infants. Higher maternal concentrations of PCB-138 and PCB-153 were associated with reduced ano-scrotal distances and higher maternal concentrations of all four PCB congeners were associated with reduced ano-penile distances. No significant associations were found between any PCB congener and any AGD measure in female newborns.This study demonstrates that intrauterine exposure to PCBs may be associated with reduced AGD in male newborns. More research is needed to reveal the implications for adult reproductive health.

Anogenital distance in newborn infants conceived by assisted reproduction and natural conception

Research questionDoes anogenital distance (AGD) differ in newborn infants conceived through assisted reproduction technology (ART) compared with those conceived naturally? DesignThis case–control study looked at anthropometric and anogenital measurements in 247 male and 200 female newborns born after ART (n = 121) or natural conception (n = 326), within 24 h of birth. Anogenital measurements included distance from the centre of the anus to the anterior clitoris (AGDAC) and to the posterior fourchette (AGDAF) in female infants, and from the centre of the anus to the posterior base of the scrotum (AGDAS) and to the anterior base of the penis (AGDAP) in male infants. ResultsART mothers were older, more likely to be nulliparous and delivered by Caesarean section at an earlier gestational week. AGDAS of male infants was approximately twice the AGDAF of female infants (17.6 ± 5.0 versus 9.1 ± 3.6 mm). AGDAF in female infants conceived by ART compared with those conceived naturally was not significantly different (8.8 ± 3.6 versus 9.3 ± 3.6 mm; P = 0.404). AGDAC were also comparable for both groups (27.4 ± 6.3 versus 27.7 ± 7.1 mm; P = 0.770). In male infants, no significant difference was seen between ART and natural conception groups in terms of AGDAS (17.4 ± 4.6 versus 17.7 ± 5.2 mm, P = 0.742) and AGDAP (37.5 ± 6.6 versus 38.0 ± 6.7 mm, P = 0.589). When adjusted for gestational age, weight, length and head circumference, mode of conception was not associated with differences in any of the anogenital measurements. ConclusionsAGD measurements in infants conceived by ART are no different from those of infants conceived naturally.

Normative data on penile and anogenital measurements of term male infants in Sagamu, Nigeria.

To document normative data on penile size and anogenital distances of apparently normal term male infants in Sagamu, Nigeria. This cross-sectional study was carried out on 303 term male infants within the first 72hours of life. Stretched penile length, penile width and three measures of anogenital distances were recorded: anogenital distance-1, anogenital distance-2 and anoscrotal distance. The mean (±SD) stretched penile length and penile width were 39.4±4.2mm and 11.0±1.0mm, respectively. The mean values for anogenital distance-1, anogenital distance-2 and the anoscrotal distance were 48.7±3.9mm, 42.8±4.6mm and 25.5±3.9mm, respectively. Only penile width and anogenital distance-1 significantly correlated with all the anthropometric parameters but anogenital distance-1 had the strongest correlation (p<0.01 for all). The observed mean stretched penile length was greater than previously reported. Local references are preferable in interpreting anogenital measurements in newborns to avoid diagnostic errors. There is need for a consensus on the definition of micropenis.

High Prenatal Exposure to Bisphenol A Reduces Anogenital Distance in Healthy Male Newborns.

Objective:To estimate the relationship between cord blood bisphenol A (BPA) levels and anogenital measurements in healthy newborns.Methods:Pregnancy and birth history, together with body mass and length data, anogenital measurements, penile measurements and cord blood samples were obtained from healthy newborns. Cord blood concentration of BPA was analyzed by sandwich enzyme-linked immunosorbent assays kit.Results:Among 130 healthy newborns (72 boys, 58 girls), mean anopenile distance was 45.2±6 mm and anoscrotal distance was 21.9±5.4 mm in boys; mean anoclitoral distance was 33.8±6.6 mm and mean anofourchette distance was 12.2±4.9 mm in girls. Mean cord blood BPA level was 4.75±2.18 ng/mL. 90th percentile value for cord blood BPA was 8.26 ng/mL and the analysis showed a statistically significant correlation between anoscrotal distance and cord blood BPA levels above the 90th percentile (p=0.047) in boys. The changes in anogenital distance in girls were not statistically significant.Conclusion:We showed a significant association between high cord blood BPA levels and shortened anoscrotal distance in male newborns. However, this result should be interpreted with caution since there were no significant external genital abnormalities in our study group.

Influence of race on prenatal phthalate exposure and anogenital measurements among boys and girls

BackgroundSelect phthalates have antiandrogenic activity, which raises concern for adverse developmental outcomes given widespread exposure of pregnant women. Investigators have reported associations between maternal urinary phthalates and altered anogenital distance (AGD), a marker of in utero androgen activity, among offspring. However, data assessing the impact of race on these associations is sparse. ObjectivesTo evaluate associations between prenatal phthalate exposure and AGD in a racially diverse newborn population. MethodsWe prospectively collected second trimester urine from 187 African American and 193 white mothers, and used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure eight phthalate metabolites and calculate molar sums. We measured anopenile (APD) and anoscrotal (ASD) distances of 171 boys and anoclitoral (ACD) and anofourchette (AFD) distances of 128 girls at delivery. We collected sociodemographic and clinical data from questionnaires and delivery records. ResultsWe identified a statistically significant inverse association for mono-2-ethylhexyl phthalate (MEHP) and APD in boys (B=−1.57mm, p=0.02), which was stronger for African Americans (B=−2.07mm, p=0.04) than for whites (B=−1.23mm, p=0.22), although the racial interaction was not statistically significant (p=0.56). We found a longer ASD for higher molar sums of dibutyl phthalate (∑DBP; B=0.99mm, p=0.04), with stronger associations for whites (B=1.30mm, p=0.04) than for African Americans (B=0.39mm, p=0.59), again without a statistically significant racial interaction (p=0.34). Among girls, we found inverse associations for tertiles of MEHP with AFD and ACD, and statistically significant race-based interactions, in which ACD was longer for whites and shorter for African Americans, following exposure to monoethyl phthalate (MEP; p=0.01) and ∑DBP (p=0.08). ConclusionsOur findings suggest race and sex play important roles in phthalate-associated reproductive developmental toxicity, with important implications for designing future investigations and health interventions.

Anogenital distance and the risk of prostate cancer

Study Type - Prognosis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? In animals, anogenital distance has been shown to be related to the action of fetal androgens, and exposure to chemicals such as dioxins that exhibit antiandrogenic activity results in shorter distances in male rats. In studies conducted in children, anogenital distance has been associated with endocrine disruptors such as phthalates. Studies conducted in young adults found that a shorter anoscrotal distance was a predictor of low sperm concentration, and a longer anoscrotal distance was associated with fatherhood, a higher sperm density and a higher total motile sperm count. The present study is the first to report anogenital measurements in adults in relation to the risk of cancer, showing that a phenotype reflecting normal in utero sexual development in males is associated with a lower risk of prostate cancer. There are two published studies evaluating sperm quality and fatherhood suggesting a connecting mechanism related to the disruption of androgen-mediated pathways in utero that affects reproductive potential and the risk of prostate cancer. • To measure anogenital distance in patients with prostate cancer and control subjects without cancer. • To evaluate the association of anogenital distance with prostate cancer in a case-control study in Spain. • Anogenital distances from anus to upper penis (AGDAP ) and from anus to scrotum (AGDAS ) were measured in 60 patients with prostate cancer in two hospitals in Barcelona and in 52 urological controls. • Each measurement was performed three times by the same trained examiner using a digital caliper • Patients had an ≈5 mm shorter AGDAP than controls, whereas no difference was observed for AGDAS . • A higher AGDAP was associated with a lower risk of prostate cancer, with an adjusted odds ratio per 5 mm increase in AGDAP of 0.83 (95% confidence interval, 0.70-0.99, P= 0.03). • The present study is the first to report anogenital measurements in adults in relation to the risk of cancer. • The present study showed that a phenotype reflecting normal in utero sexual development in men is associated with a lower risk of prostate cancer. • There are two published studies (Mendiola et al. Environ Health Perspect 2011; 119: 958-63; Eisenberg et al. PLoS One 2011; 6: e18973) evaluating sperm quality and fatherhood suggesting a connecting mechanism related to the disruption of androgen-mediated pathways in utero that affects reproductive potential and the risk of prostate cancer.

A pilot study of the association between genetic polymorphisms involved in estrogen signaling and infant male genital phenotypes

Single nucleotide polymorphisms (SNPs) in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance (AGD), anoscrotal distance (ASD) and penile width (PW). We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families. We used DNA from buccal smears and linear regression models to assess the relationship between anogenital measurements and SNP genotypes with adjustment for covariates. We found that the rs2077647 G allele, located in the coding region of estrogen receptor alpha (ESR1), was associated with a shorter AGD (P=0.02; -7.3 mm, 95% confidence interval (CI): -11.6 to -3.1), and the rs10475 T allele, located in the 3' untranslated region of activating transcription factor 3 (ATF3), was associated with a shorter ASD (-4.3 mm, 95% CI: -7.2 to -1.4), although this result was not significant (P=0.07) after controlling for multiple comparisons. We observed no association between PW and the SNPs tested. Minor alleles for two SNPs in genes that regulate estrogen signaling during male genital development were associated with AGD and ASD, although the significance of the association was marginal. Our findings suggest that AGD and ASD are influenced by heritable factors in genes known to be associated with frank male genital abnormalities such as hypospadias and cryptorchidism.

Anogenital Measurements in Newborns

We would like to thank Oguz Kutlu A for her close interest in our paper entitled “Anogenital Distance in Turkish Newborns”. In our study (1), we used caliper for the measurements as Oguz Kutlu A did in her study (2). We compared our anogenital measurements to those obtained in previous studies in the literature (including Oguz Kutlu’s study) according to the measurement method used, as shown in the table below. Although different measurement methods were applied, our results were similar to those from the mentioned studies. Variations in the results reported can be due to genetic and ethnic factors, as well as to the measurement methods used and the age of the newborn at the time of the measurements, as it was emphasized in the discussion section of our paper (3). However, anogenital distance measurement method used in the study by Oguz Kutlu A, was wrongly written as tape measurement instead of caliper measurement (2). We are, again, giving the original table including correct measurement technique belonging to Oguz Kutlu A. In addition, I would like to thank her for giving extra information about the genital measurements in the Letter.

Anogenital distance as a marker of in-utero hormonal exposures, and breast and prostate cancer risk. A pilot study.

Background and aims. Several lines of evidence indicate that foetal exposures may be related with adult breast and prostate cancer. Anogenital distance is a sexually dimorphic phenotype that has been shown in animals to be related to foetal androgen action and that tracks through life. Anogenital distance has been scarcely used in human studies. A single study in adults found that shorter anogenital distance was a predictor of low sperm concentration. We evaluated the association of anogenital distance with breast and prostate cancer risk in a pilot study within a large population based case-control study in Spain (MCC-Sp). Methods: Cases were identified at the Hospital del Mar, Barcelona and population controls were residents in the catchment area of the hospital. Anoclitoral (ACD: anus to clitoris) and anofourchetal distance (AFD: anus to fourchette) were measured in 46 breast cancers cases and 19 population controls. Anogenital distance (AGD: anus to upper penis), anoscrotal distance (ASD: anus to scrotum) were measured in 58 prostate cancer cases and 5 population controls. Odds ratios were adjusted for age, examiner, BMI (or weight and height) and parity (women). Results: Anogenital distances were wider in males (mean AGD=120.7mm, SD=13.0; mean ASD = 35.8mm, SD=12.4) than females (mean ACD=102.5, SD=12.8; mean AFD=28.7, SD=6.6). No differences were observed for breast cancer (Odds Ratio (OR) for AGD=0.99, 95%CI 0.93-1.05; OR for AFD=1.09, 0.97-1.23). Shorter AGD (OR=0.85, 0.74-0.98) and ASD (OR=0.92, 0.84-1.01) were associated with a lower prostate cancer risk, although based on very small numbers. Conclusions: This is the first study reporting anogenital measurements in adults in relation to cancer risk. Results are preliminary and, if confirmed, may indicate that prostate cancer is associated with lower levels of androgens in utero. The study is ongoing and results for a larger population sample will be presented.

Anogenital Distance in Turkish Newborns

Objective: Anogenital distances are considered to be a sensitive indicator of external genitalia exposure to factors such as anti-androgens, and/or endocrine distruptors during the prenatal period. Exposure to such factors can lead to changes in the anogenital measurements (AGM) of newborn infants. These measurements can be used to predict masculinization of the external genitalia in healthy newborns. The goal of this study was to determine normal values for AGM in Turkish newborns of both genders. Methods: One hundred fifteen female and 135 male term newborns with no congenital defects were included in this study. A well-trained observer measured the anogenital distance by using a sliding Caliper graduated in millimeters. Anogenital distance was measured from the center of the anus to the posterior convergence of the fourchette in females and from the center of the anus to the junction of the smooth perineal skin with the base of the scrotum in males. Results: Anogenital distance in males and females was 23±0.6 mm and 10.3±0.2 mm, respectively. There were significant differences in anogenital distance values between male and female newborns (p<0.05). Conclusion: The findings of this study provide data that can be used as reference standards with regard to AGM of the posterior genital structures in Turkish male and female newborns. These data will also serve in postnatal evaluations to determine the effects of prenatal exposures to factors affecting development of genitalia. Conflict of interest:None declared.

Comparison of the acetophenone derivative 16alpha,17alpha-dihydroxyprogesterone with other progestational steroids for masculinization of the ratfetus.

A new progestational steroid, the acetophenone derivative of 16α,17α;- dihydroxyprogesterone, was compared with several progestogens for masculinizing effects on the offspring of rats treated during pregnancy. The results were similar to those obtained with progesterone and 17α-hydroxyprogesterone caproate: this new steroid did not alter the normal male:female sex ratio and did not virilize the internal or external sex structures of the newborn. The present results confirm those of others in finding that 6α-methyl-17α-hydroxyprogesterone acetate, 17α-ethinyl-19-nortestosterone and 17aethinyl- 19-nortestosterone acetate increased the number of male and intersex offspring, as determined by ano-genital measurements and masculinization of internal and external sex organs.