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Shanna H Swan - One of the best experts on this subject based on the ideXlab platform.

  • digit ratio a proposed marker of the prenatal hormone environment is not associated with prenatal sex steroids Anogenital Distance or gender typed play behavior in preschool age children
    Journal of Developmental Origins of Health and Disease, 2020
    Co-Authors: Emily S Barrett, Sheela Sathyanarayana, Ruby H N Nguyen, Christina Wang, Sally W Thurston, Donald Harrington, Nicole R Bush, Alexis Zavez, Shanna H Swan
    Abstract:

    Prenatal hormones have been proposed as key factors impacting child development as well as long-term health and disease. Digit ratio (the ratio of the lengths of the second to fourth digits; 2D:4D) has been proposed as a sexually dimorphic, noninvasive marker of prenatal androgen exposure that can be reliably measured in children and adults. To date, few longitudinal pregnancy cohort studies have examined childhood digit ratio in relation to other relevant measures including prenatal hormones and androgen-sensitive outcomes. To augment the current literature on this topic, we measured right-hand digit ratio in 4-year-old children participating in The Infant Development and the Environment Study, a multicenter longitudinal cohort study that has been following mother-child dyads since the first trimester of pregnancy (n = 321). We assessed sex differences in digit ratio and fit multivariable linear regression models to examine digit ratio in relation to: (1) child sex; (2) maternal sex steroid hormone concentrations in early pregnancy; (3) newborn Anogenital Distance, another proposed measure of sensitivity to prenatal androgens; and (4) gender-typical play behavior as measured by the Preschool Activities Inventory (PSAI) at age 4. We observed no sex difference in digit ratio; the mean 2D:4D was 0.97 ± 0.05 mm in both sexes. Furthermore, digit ratio was not associated with maternal sex steroid concentrations in early pregnancy, Anogenital Distance in either sex, or PSAI scores in either sex in covariate-adjusted models. In conclusion, we observed no evidence that early childhood digit ratio was associated with child sex or hormone-sensitive measures in this cohort.

  • Anogenital Distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure
    Journal of Developmental Origins of Health and Disease, 2018
    Co-Authors: Emily S Barrett, Sheela Sathyanarayana, Ruby H N Nguyen, J B Redmon, Kathleen M Hoeger, David H Abbott, Shanna H Swan
    Abstract:

    Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, Anogenital Distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette Distance (AGD-AF) and anoclitoral Distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls' AGD. In total, 300 mother-daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

  • prenatal exposure to antifungal medication may change Anogenital Distance in male offspring a preliminary study
    Environmental Health, 2017
    Co-Authors: Djamilla Madelung Mogensen, Niels E Skakkebaek, Shanna H Swan, Henriette Boye Kyhl, David Mobjerg Kristensen, Maria Bergkvist Pihl, Helle Raun Andersen, Anders Juul, Marianne Andersen, Dorte Vesterholm Lind
    Abstract:

    Vaginal candidiasis is frequent among pregnant women and it is treated with anti-fungal medication (conazoles). Conazoles have anti-androgenic properties and prenatal exposure in rodents is associated with a shorter (less masculine) Anogenital Distance (AGD) in male offspring. To our knowledge this has never been studied in humans. In the Odense Child Cohort pregnant women residing in Odense municipality, Denmark, were recruited at gestational age 8–16 weeks between 2010 and 2012. Of the eligible 2421 mother-child pairs, 812 mother-son pairs were included. Questionnaire data on medicine use were collected in first and third trimester and physical examination at age 3 month was performed. Ano-scrotal Distance; measured from the centre of anus to the posterior base of scrotum (AGDas). Ano-cephalad Distance; measured from the centre of anus to the cephalad insertion of the penis (AGDap) and penile width; measured at the base of the penis. Eighty seven women had used antifungal medicine during pregnancy. Maternal use of oral fluconazole (n = 4) was associated with a 6.4 mm shorter AGDas (95% CI: -11.9;-0.9) in the male offspring. Use of antifungal vaginal tablets (n = 21), was associated with a non-significantly shorter AGDas (−1.9 mm; 95% CI: -4.3; 0.5) whereas exposure to vaginal cream (n = 23) was not associated to AGDas. Use of antifungal medicine in the window of genital development between 8 and 14 weeks of gestation was associated with a larger reduction in AGDas than exposure outside this window. Antifungal medicine intake was not associated with AGDap and penil width. Our preliminary findings prompted us to hypothesize that maternal use of conazole antifungal medication during pregnancy may affect the masculinization of male offspring. If confirmed, pregnant women should be advised to use antifungal medicine with caution.

  • manipulation of pre and postnatal androgen environments and Anogenital Distance in rats
    Toxicology, 2016
    Co-Authors: Diogo Henrique Kita, Shanna H Swan, Katlyn Barp Meyer, Amanda Caroline Venturelli, Rafaella Adams, Daria Louise Barbosa Machado, Rosana Nogueira De Morais, Chris Gennings, Anderson Joel Martinoandrade
    Abstract:

    Abstract We examined the Anogenital Distance (AGD) plasticity in rats through the manipulation of the androgen environment in utero and during puberty. Dams were treated from gestation days 13–20 with vehicle, flutamide (20 mg/kg/day), di-(2-ethylhexyl) phthalate (DEHP, 750 mg/kg/day), or testosterone (1.0 mg/kg/day). After weaning, male pups were randomly assigned to one of four postnatal groups, which received the same treatments given prenatally. Sixteen treatment groups were established based on the combination of pre- and postnatal exposures. The postnatal treatments were conducted from postnatal days 23–53. In utero flutamide and DEHP exposure significantly shortened male AGD, although this effect was more pronounced in flutamide-exposed rats. Postnatal flutamide, DEHP, and testosterone induced slight but significant reductions in male AGD. Our study indicates that AGD is a stable anatomical landmark that reflects the androgen action in utero , although it can also be slightly responsive to changes in the androgen environment following pubertal exposure.

  • comparability and reproducibility of adult male Anogenital Distance measurements for two different methods
    Journal of Andrology, 2016
    Co-Authors: Jaime Mendiola, Michael L Eisenberg, Julian Onateceldran, Paula Sampermateo, Julian J Arensegonzalo, Marcos Torresroca, C Sanchezrodriguez, Damian Garciaescudero, L O Fontanacompiano, Shanna H Swan
    Abstract:

    Summary The Distance from the genitals to the anus, Anogenital Distance, reflects androgen concentration during prenatal development in mammals. The use of Anogenital Distance in human studies is still very limited and the quality and consistency of measurements is an important methodological issue. The aim of this study was to assess the feasibility and reproducibility of adult male Anogenital Distance measurements by two different methods. All men were attending an outpatient clinic at a university hospital and underwent an andrological examination and completed a brief questionnaire. Two variants of Anogenital Distance [from the anus to the posterior base of the scrotum (AGDAS) and to the cephalad insertion of the penis (AGDAP)] by two methods (lithotomy or frog-legged position) were assessed in 70 men. Within and between coefficient of variations, intra-class correlation coefficients, two-way repeated-measures analysis of variance, and scatter and Bland–Altman plots were calculated. The two methods produced similar values for AGDAP but different estimates for AGDAS. Nonetheless, the overall agreement (ICC ≥ 0.80) was acceptable for both measures. Therefore, both methods are internally consistent and adequate for epidemiological studies, and may be used depending on the available medical resources, clinical setting, and populations.

Michael L Eisenberg - One of the best experts on this subject based on the ideXlab platform.

  • comparability and reproducibility of adult male Anogenital Distance measurements for two different methods
    Journal of Andrology, 2016
    Co-Authors: Jaime Mendiola, Michael L Eisenberg, Julian Onateceldran, Paula Sampermateo, Julian J Arensegonzalo, Marcos Torresroca, C Sanchezrodriguez, Damian Garciaescudero, L O Fontanacompiano, Shanna H Swan
    Abstract:

    Summary The Distance from the genitals to the anus, Anogenital Distance, reflects androgen concentration during prenatal development in mammals. The use of Anogenital Distance in human studies is still very limited and the quality and consistency of measurements is an important methodological issue. The aim of this study was to assess the feasibility and reproducibility of adult male Anogenital Distance measurements by two different methods. All men were attending an outpatient clinic at a university hospital and underwent an andrological examination and completed a brief questionnaire. Two variants of Anogenital Distance [from the anus to the posterior base of the scrotum (AGDAS) and to the cephalad insertion of the penis (AGDAP)] by two methods (lithotomy or frog-legged position) were assessed in 70 men. Within and between coefficient of variations, intra-class correlation coefficients, two-way repeated-measures analysis of variance, and scatter and Bland–Altman plots were calculated. The two methods produced similar values for AGDAP but different estimates for AGDAS. Nonetheless, the overall agreement (ICC ≥ 0.80) was acceptable for both measures. Therefore, both methods are internally consistent and adequate for epidemiological studies, and may be used depending on the available medical resources, clinical setting, and populations.

  • Anogenital Distance as a measure of human male fertility
    Journal of Assisted Reproduction and Genetics, 2015
    Co-Authors: Michael L Eisenberg, Larry I. Lipshultz
    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.

  • the relationship between Anogenital Distance and the androgen receptor cag repeat length
    Asian Journal of Andrology, 2013
    Co-Authors: Michael L Eisenberg, Tungchin Hsieh, Rustin C Walters, Alexander W Pastuszak, Matthew G Mcintyre, Dolores J Lamb, Larry I. Lipshultz
    Abstract:

    Anogenital Distance (AGD) is used to define degree of virilization of genital development, with shorter length being associated with feminization and male infertility. The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine–adenine–guanine (CAG) repeats, with longer CAG repeat lengths being associated with decreased receptor function. We sought to determine if there is an association between AGD and AR CAG repeat length. A cross-sectional, prospective cohort of men evaluated at a urology clinic at a single institution was recruited. AGD (the Distance from the posterior scrotum to the anal verge) and penile length (PL) were measured. Sanger DNA sequence analysis was used to define CAG repeat length. AGD and CAG repeat lengths in 195 men were determined. On unadjusted analysis, there was no linear relationship between CAG repeat length and PL (P=0.17) or AGD (P=0.31). However, on sub-population analyses, those men with longer CAG repeat lengths (>26) had significantly shorter AGDs compared to men with shorter CAG repeat lengths. For example, the mean AGD was 41.9 vs. 32.4 mm with a CAG repeat length ≤26 vs. >26 (P=0.01). In addition, when stratifying the cohort based on AGD, those with AGD less than the median (i.e. 40 mm) had a longer CAG repeat length compared to men with an AGD >40 mm (P=0.02). In summary, no linear relationship was found between AGD and AR CAG repeat length overall.

  • the relationship between Anogenital Distance and age
    Journal of Andrology, 2013
    Co-Authors: Michael L Eisenberg, Tungchin Hsieh, Larry I. Lipshultz
    Abstract:

    In humans, recent studies have correlated Anogenital Distance (AGD) in adult men to intrinsic testicular function. Although rodent studies suggest that AGD is determined in utero and remains constant in adult life, it is not certain if AGD remains constant across a man's adult life. We sought to determine if adult male AGD varies based on age. A cross-sectional study of men being evaluated at a men's health clinic. Anogenital Distance (the Distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital callipers. anova and linear regression were used to determine correlations between AGD, fatherhood status and age. In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. The mean AGD for the group was 39 ± 13 mm. Anogenital Distance did not vary between age categories for the entire group, for fathers, and for childless men. Moreover, penile length also remained constant across age categories. On adjusted analyses stratified by fatherhood status, there was no relationship between AGDp and age. The current cross-sectional study demonstrates that Anogenital Distance, defined as the Distance from the posterior scrotum to the anal verge, is similar for men of different ages. As such, AGD may provide a measure for genital development and function throughout adult life. However, confirmation with longitudinal studies is needed.

  • the relationship between Anogenital Distance and azoospermia in adult men
    International Journal of Andrology, 2012
    Co-Authors: Michael L Eisenberg, Chanc R Walters, Michael E Shy, Larry I. Lipshultz
    Abstract:

    Anogenital Distance (AGD) is a marker for endocrine disruption in animal studies in which decreased male AGD has been associated with testicular dysfunction. The objective of the study was to investigate whether Anogenital Distance 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 ± 9.2) and 29 NOA men (mean age: 32.8 ± 4.8) were recruited. The NOA men possessed significantly shorter mean AGD than the men with OA (AGD: 36.3 vs. 41.9 mm, p = 0.01). An AGD of less than 30 mm, had a 91% specificity in accurately classifying NOA. Moreover, after adjustment for age, race, and BMI, an AGD of less than 30 mm yielded a significantly 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.

Larry I. Lipshultz - One of the best experts on this subject based on the ideXlab platform.

  • Anogenital Distance as a measure of human male fertility
    Journal of Assisted Reproduction and Genetics, 2015
    Co-Authors: Michael L Eisenberg, Larry I. Lipshultz
    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.

  • the relationship between Anogenital Distance and the androgen receptor cag repeat length
    Asian Journal of Andrology, 2013
    Co-Authors: Michael L Eisenberg, Tungchin Hsieh, Rustin C Walters, Alexander W Pastuszak, Matthew G Mcintyre, Dolores J Lamb, Larry I. Lipshultz
    Abstract:

    Anogenital Distance (AGD) is used to define degree of virilization of genital development, with shorter length being associated with feminization and male infertility. The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine–adenine–guanine (CAG) repeats, with longer CAG repeat lengths being associated with decreased receptor function. We sought to determine if there is an association between AGD and AR CAG repeat length. A cross-sectional, prospective cohort of men evaluated at a urology clinic at a single institution was recruited. AGD (the Distance from the posterior scrotum to the anal verge) and penile length (PL) were measured. Sanger DNA sequence analysis was used to define CAG repeat length. AGD and CAG repeat lengths in 195 men were determined. On unadjusted analysis, there was no linear relationship between CAG repeat length and PL (P=0.17) or AGD (P=0.31). However, on sub-population analyses, those men with longer CAG repeat lengths (>26) had significantly shorter AGDs compared to men with shorter CAG repeat lengths. For example, the mean AGD was 41.9 vs. 32.4 mm with a CAG repeat length ≤26 vs. >26 (P=0.01). In addition, when stratifying the cohort based on AGD, those with AGD less than the median (i.e. 40 mm) had a longer CAG repeat length compared to men with an AGD >40 mm (P=0.02). In summary, no linear relationship was found between AGD and AR CAG repeat length overall.

  • the relationship between Anogenital Distance and age
    Journal of Andrology, 2013
    Co-Authors: Michael L Eisenberg, Tungchin Hsieh, Larry I. Lipshultz
    Abstract:

    In humans, recent studies have correlated Anogenital Distance (AGD) in adult men to intrinsic testicular function. Although rodent studies suggest that AGD is determined in utero and remains constant in adult life, it is not certain if AGD remains constant across a man's adult life. We sought to determine if adult male AGD varies based on age. A cross-sectional study of men being evaluated at a men's health clinic. Anogenital Distance (the Distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital callipers. anova and linear regression were used to determine correlations between AGD, fatherhood status and age. In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. The mean AGD for the group was 39 ± 13 mm. Anogenital Distance did not vary between age categories for the entire group, for fathers, and for childless men. Moreover, penile length also remained constant across age categories. On adjusted analyses stratified by fatherhood status, there was no relationship between AGDp and age. The current cross-sectional study demonstrates that Anogenital Distance, defined as the Distance from the posterior scrotum to the anal verge, is similar for men of different ages. As such, AGD may provide a measure for genital development and function throughout adult life. However, confirmation with longitudinal studies is needed.

  • the relationship between Anogenital Distance and azoospermia in adult men
    International Journal of Andrology, 2012
    Co-Authors: Michael L Eisenberg, Chanc R Walters, Michael E Shy, Larry I. Lipshultz
    Abstract:

    Anogenital Distance (AGD) is a marker for endocrine disruption in animal studies in which decreased male AGD has been associated with testicular dysfunction. The objective of the study was to investigate whether Anogenital Distance 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 ± 9.2) and 29 NOA men (mean age: 32.8 ± 4.8) were recruited. The NOA men possessed significantly shorter mean AGD than the men with OA (AGD: 36.3 vs. 41.9 mm, p = 0.01). An AGD of less than 30 mm, had a 91% specificity in accurately classifying NOA. Moreover, after adjustment for age, race, and BMI, an AGD of less than 30 mm yielded a significantly 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.

  • the relationship between Anogenital Distance and reproductive hormone levels in adult men
    The Journal of Urology, 2012
    Co-Authors: Michael L Eisenberg, Chanc R Walters, Niels E Skakkebaek, Tina Kold Jensen, Larry I. Lipshultz
    Abstract:

    Purpose: Anogenital Distance is a marker for endocrine disruption in animal studies in which decreased Distance has been associated with testicular dysfunction. 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 examination. Linear regression was used to determine correlations between genital measurements and hormone levels.Results: Anogenital Distance (r = 0.20, p = 0.03) and penile length (r = 0.20, p = 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 iden...

Sheela Sathyanarayana - One of the best experts on this subject based on the ideXlab platform.

  • maternal urinary levels of glyphosate during pregnancy and Anogenital Distance in newborns in a us multicenter pregnancy cohort
    Environmental Pollution, 2021
    Co-Authors: Corina Lesseur, Emily S Barrett, Ruby H N Nguyen, Patrick Pirrotte, Khyatiben V Pathak, Fabiana Manservisi, Daniele Mandrioli, Fiorella Belpoggi, Simona Panzacchi, Sheela Sathyanarayana
    Abstract:

    Abstract Human exposure to glyphosate has become ubiquitous because of its increasing agricultural use. Recent studies suggest endocrine disrupting effects of glyphosate. Specifically, in our work in rodents, low-dose early-life exposure to Roundup® (glyphosate-based herbicide) lengthened Anogenital Distance (AGD) in male and female offspring. AGD is a marker of the prenatal hormone milieu in rodents and humans. The relationship between glyphosate exposure and AGD has not been studied in humans. We conducted a pilot study in 94 mother-infant pairs (45 female and 49 male) from The Infant Development and the Environment Study (TIDES). For each infant, two AGD measurements were collected after birth; the anopenile (AGD-AP) and anoscrotal (AGD-AS) Distances for males, and anoclitoral (AGD-AC) and anofourchette Distances (AGD-AF) for females. We measured levels of glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in 2nd trimester maternal urine samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. We assessed the relationship between exposure and AGD using sex-stratified multivariable linear regression models. Glyphosate and AMPA were detected in 95% and 93% of the samples (median 0.22 ng/mL and 0.14 ng/mL, respectively). Their concentrations were moderately correlated (r = 0.55, p = 5.7 × 10−9). In female infants, high maternal urinary glyphosate (above the median) was associated with longer AGD-AC (β = 1.48, 95%CI (−0.01, 3.0), p = 0.05), but this was not significant after covariate adjustment. Increased AMPA was associated with longer AGD-AF (β = 1.96, 95%CI (0.44, 3.5), p = 0.01) after adjusting for infant size and age at AGD exam. No associations were detected in male offspring. These preliminary findings partially reproduce our previous results in rodents and suggest that glyphosate is a sex-specific endocrine disruptor with androgenic effects in humans. Given the increasing glyphosate exposures in the US population, larger studies should evaluate potential developmental effects on endocrine and reproductive systems.

  • digit ratio a proposed marker of the prenatal hormone environment is not associated with prenatal sex steroids Anogenital Distance or gender typed play behavior in preschool age children
    Journal of Developmental Origins of Health and Disease, 2020
    Co-Authors: Emily S Barrett, Sheela Sathyanarayana, Ruby H N Nguyen, Christina Wang, Sally W Thurston, Donald Harrington, Nicole R Bush, Alexis Zavez, Shanna H Swan
    Abstract:

    Prenatal hormones have been proposed as key factors impacting child development as well as long-term health and disease. Digit ratio (the ratio of the lengths of the second to fourth digits; 2D:4D) has been proposed as a sexually dimorphic, noninvasive marker of prenatal androgen exposure that can be reliably measured in children and adults. To date, few longitudinal pregnancy cohort studies have examined childhood digit ratio in relation to other relevant measures including prenatal hormones and androgen-sensitive outcomes. To augment the current literature on this topic, we measured right-hand digit ratio in 4-year-old children participating in The Infant Development and the Environment Study, a multicenter longitudinal cohort study that has been following mother-child dyads since the first trimester of pregnancy (n = 321). We assessed sex differences in digit ratio and fit multivariable linear regression models to examine digit ratio in relation to: (1) child sex; (2) maternal sex steroid hormone concentrations in early pregnancy; (3) newborn Anogenital Distance, another proposed measure of sensitivity to prenatal androgens; and (4) gender-typical play behavior as measured by the Preschool Activities Inventory (PSAI) at age 4. We observed no sex difference in digit ratio; the mean 2D:4D was 0.97 ± 0.05 mm in both sexes. Furthermore, digit ratio was not associated with maternal sex steroid concentrations in early pregnancy, Anogenital Distance in either sex, or PSAI scores in either sex in covariate-adjusted models. In conclusion, we observed no evidence that early childhood digit ratio was associated with child sex or hormone-sensitive measures in this cohort.

  • prenatal perfluoroalkyl substances and newborn Anogenital Distance in a canadian cohort
    Reproductive Toxicology, 2020
    Co-Authors: Tye E Arbuckle, Sheela Sathyanarayana, Susan Macpherson, Warren G Foster, Mandy Fisher, Patricia Monnier, Bruce P Lanphear, Gina Muckle, William D Fraser
    Abstract:

    Exposure to the man-made chemicals perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) is widespread. These perfluoroalkyl substances (PFASs) have been associated with androgenic endocrine-disrupting properties; however, the evidence is equivocal and few human studies have examined the association between prenatal exposure to PFASs and markers of androgenic endocrine disruption such as changes in Anogenital Distance (AGD). In the MIREC cohort, PFOA, PFOS and PFHxS were analyzed in first trimester maternal plasma. AGD was measured in 205 male and 196 female newborns. The change in estimate procedure was used to identify confounders by sex and AGD in multiple linear regression models. Geometric mean plasma concentrations (95% CI) for PFOA, PFOS and PFHxS were 1.71 (1.61, 1.81), 4.40 (4.18, 4.64) and 1.15 (1.06, 1.25) μg/L, respectively. A one-unit increase in natural log transformed PFOA was associated with a 1.36 mm (95% CI 0.30, 2.41) increase in anoscrotal Distance, adjusting for household income, active smoking status during pregnancy and gestational age. However, when examined by quartiles, a non-monotonic pattern was observed with wide confidence intervals. No consistent patterns were observed between maternal PFAS concentrations and female AGDs. This study found no clear evidence that maternal plasma concentrations of PFOS, PFOA or PFHxS were associated with shorter infant Anogenital Distance in males or any change in AGD in females. Whether the positive association observed between longer anoscrotal Distance and PFOA is real or would have any long-lasting effect on the reproductive health of males is unknown and needs to be investigated further.

  • do stressful life events during pregnancy modify associations between phthalates and Anogenital Distance in newborns
    Environmental Research, 2019
    Co-Authors: Tye E Arbuckle, Emily S Barrett, Sheela Sathyanarayana, Susan Macpherson, Warren G Foster, Mandy Fisher, Gina Muckle, Jean R Seguin, Linda Dodds, Amisha Agarwal
    Abstract:

    Anogenital Distance (AGD) has been used as a marker of fetal androgen action to identify endocrine disrupting chemicals. A US study (TIDES) has reported that the association between some phthalates and reduced AGD in males was only apparent in sons of mothers reporting no stressful life events (SLEs) during pregnancy. The objective of the current study was to examine the potential modifying effect of SLEs and their subjective impact on associations between prenatal phthalates and AGD. First trimester urines from the MIREC Study were analysed for phthalate metabolites and AGD was measured in neonates. Post-delivery, the women answered questions on SLEs during the pregnancy. Women reporting 1 or more SLEs during pregnancy were considered a "higher stressor" group, whereas women reporting no SLEs or who reported a SLE that was perceived as not at all stressful were considered a "lower stressor" group. Multivariable linear regression models were fit stratified by stressor group. Maternal stressor, AGD and phthalates results were available for 153 females and 147 males. A summary measure of androgen-disrupting phthalates (Σ AD) was associated with significantly longer AGDs in females from the higher stressor group. These effect sizes were increased when the perceived impact was restricted to moderately or very much stressful. In males, all phthalates were associated with longer anopenile Distance (APD), regardless of stressor group; however, higher Σ AD was associated with significantly longer APD in the lower stressor group. In contrast to the TIDES study, we did not observe shorter AGDs in male infants prenatally exposed to di-(2-ethylhexyl) phthalates, regardless of maternal stressor level. In conclusion, we were unable to replicate the findings of the TIDES study, but did find some evidence that prenatal SLEs may modify associations between phthalates and female AGD. Further research with other populations and measures of prenatal stress may shed more light on whether prenatal stress is an important effect modifier of associations between phthalates (or other chemicals) and Anogenital Distance.

  • Anogenital Distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure
    Journal of Developmental Origins of Health and Disease, 2018
    Co-Authors: Emily S Barrett, Sheela Sathyanarayana, Ruby H N Nguyen, J B Redmon, Kathleen M Hoeger, David H Abbott, Shanna H Swan
    Abstract:

    Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, Anogenital Distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette Distance (AGD-AF) and anoclitoral Distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls' AGD. In total, 300 mother-daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

Emily S Barrett - One of the best experts on this subject based on the ideXlab platform.

  • maternal urinary levels of glyphosate during pregnancy and Anogenital Distance in newborns in a us multicenter pregnancy cohort
    Environmental Pollution, 2021
    Co-Authors: Corina Lesseur, Emily S Barrett, Ruby H N Nguyen, Patrick Pirrotte, Khyatiben V Pathak, Fabiana Manservisi, Daniele Mandrioli, Fiorella Belpoggi, Simona Panzacchi, Sheela Sathyanarayana
    Abstract:

    Abstract Human exposure to glyphosate has become ubiquitous because of its increasing agricultural use. Recent studies suggest endocrine disrupting effects of glyphosate. Specifically, in our work in rodents, low-dose early-life exposure to Roundup® (glyphosate-based herbicide) lengthened Anogenital Distance (AGD) in male and female offspring. AGD is a marker of the prenatal hormone milieu in rodents and humans. The relationship between glyphosate exposure and AGD has not been studied in humans. We conducted a pilot study in 94 mother-infant pairs (45 female and 49 male) from The Infant Development and the Environment Study (TIDES). For each infant, two AGD measurements were collected after birth; the anopenile (AGD-AP) and anoscrotal (AGD-AS) Distances for males, and anoclitoral (AGD-AC) and anofourchette Distances (AGD-AF) for females. We measured levels of glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in 2nd trimester maternal urine samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. We assessed the relationship between exposure and AGD using sex-stratified multivariable linear regression models. Glyphosate and AMPA were detected in 95% and 93% of the samples (median 0.22 ng/mL and 0.14 ng/mL, respectively). Their concentrations were moderately correlated (r = 0.55, p = 5.7 × 10−9). In female infants, high maternal urinary glyphosate (above the median) was associated with longer AGD-AC (β = 1.48, 95%CI (−0.01, 3.0), p = 0.05), but this was not significant after covariate adjustment. Increased AMPA was associated with longer AGD-AF (β = 1.96, 95%CI (0.44, 3.5), p = 0.01) after adjusting for infant size and age at AGD exam. No associations were detected in male offspring. These preliminary findings partially reproduce our previous results in rodents and suggest that glyphosate is a sex-specific endocrine disruptor with androgenic effects in humans. Given the increasing glyphosate exposures in the US population, larger studies should evaluate potential developmental effects on endocrine and reproductive systems.

  • digit ratio a proposed marker of the prenatal hormone environment is not associated with prenatal sex steroids Anogenital Distance or gender typed play behavior in preschool age children
    Journal of Developmental Origins of Health and Disease, 2020
    Co-Authors: Emily S Barrett, Sheela Sathyanarayana, Ruby H N Nguyen, Christina Wang, Sally W Thurston, Donald Harrington, Nicole R Bush, Alexis Zavez, Shanna H Swan
    Abstract:

    Prenatal hormones have been proposed as key factors impacting child development as well as long-term health and disease. Digit ratio (the ratio of the lengths of the second to fourth digits; 2D:4D) has been proposed as a sexually dimorphic, noninvasive marker of prenatal androgen exposure that can be reliably measured in children and adults. To date, few longitudinal pregnancy cohort studies have examined childhood digit ratio in relation to other relevant measures including prenatal hormones and androgen-sensitive outcomes. To augment the current literature on this topic, we measured right-hand digit ratio in 4-year-old children participating in The Infant Development and the Environment Study, a multicenter longitudinal cohort study that has been following mother-child dyads since the first trimester of pregnancy (n = 321). We assessed sex differences in digit ratio and fit multivariable linear regression models to examine digit ratio in relation to: (1) child sex; (2) maternal sex steroid hormone concentrations in early pregnancy; (3) newborn Anogenital Distance, another proposed measure of sensitivity to prenatal androgens; and (4) gender-typical play behavior as measured by the Preschool Activities Inventory (PSAI) at age 4. We observed no sex difference in digit ratio; the mean 2D:4D was 0.97 ± 0.05 mm in both sexes. Furthermore, digit ratio was not associated with maternal sex steroid concentrations in early pregnancy, Anogenital Distance in either sex, or PSAI scores in either sex in covariate-adjusted models. In conclusion, we observed no evidence that early childhood digit ratio was associated with child sex or hormone-sensitive measures in this cohort.

  • do stressful life events during pregnancy modify associations between phthalates and Anogenital Distance in newborns
    Environmental Research, 2019
    Co-Authors: Tye E Arbuckle, Emily S Barrett, Sheela Sathyanarayana, Susan Macpherson, Warren G Foster, Mandy Fisher, Gina Muckle, Jean R Seguin, Linda Dodds, Amisha Agarwal
    Abstract:

    Anogenital Distance (AGD) has been used as a marker of fetal androgen action to identify endocrine disrupting chemicals. A US study (TIDES) has reported that the association between some phthalates and reduced AGD in males was only apparent in sons of mothers reporting no stressful life events (SLEs) during pregnancy. The objective of the current study was to examine the potential modifying effect of SLEs and their subjective impact on associations between prenatal phthalates and AGD. First trimester urines from the MIREC Study were analysed for phthalate metabolites and AGD was measured in neonates. Post-delivery, the women answered questions on SLEs during the pregnancy. Women reporting 1 or more SLEs during pregnancy were considered a "higher stressor" group, whereas women reporting no SLEs or who reported a SLE that was perceived as not at all stressful were considered a "lower stressor" group. Multivariable linear regression models were fit stratified by stressor group. Maternal stressor, AGD and phthalates results were available for 153 females and 147 males. A summary measure of androgen-disrupting phthalates (Σ AD) was associated with significantly longer AGDs in females from the higher stressor group. These effect sizes were increased when the perceived impact was restricted to moderately or very much stressful. In males, all phthalates were associated with longer anopenile Distance (APD), regardless of stressor group; however, higher Σ AD was associated with significantly longer APD in the lower stressor group. In contrast to the TIDES study, we did not observe shorter AGDs in male infants prenatally exposed to di-(2-ethylhexyl) phthalates, regardless of maternal stressor level. In conclusion, we were unable to replicate the findings of the TIDES study, but did find some evidence that prenatal SLEs may modify associations between phthalates and female AGD. Further research with other populations and measures of prenatal stress may shed more light on whether prenatal stress is an important effect modifier of associations between phthalates (or other chemicals) and Anogenital Distance.

  • Anogenital Distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure
    Journal of Developmental Origins of Health and Disease, 2018
    Co-Authors: Emily S Barrett, Sheela Sathyanarayana, Ruby H N Nguyen, J B Redmon, Kathleen M Hoeger, David H Abbott, Shanna H Swan
    Abstract:

    Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, Anogenital Distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette Distance (AGD-AF) and anoclitoral Distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls' AGD. In total, 300 mother-daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

  • human chorionic gonadotropin partially mediates phthalate association with male and female Anogenital Distance
    The Journal of Clinical Endocrinology and Metabolism, 2015
    Co-Authors: Jennifer J Adibi, Emily S Barrett, Sheela Sathyanarayana, Bruce J Redmon, Ruby H N Nguyen, Myoung Keun Lee, Ashley I Naimi, Yaqi Zhao, Mari Paule Thiet, Shanna H Swan
    Abstract:

    Context: Prenatal exposure to phthalates disrupts male sex development in rodents. In humans, the placental glycoprotein hormone human chorionic gonadotropin (hCG) is required for male development, and may be a target of phthalate exposure. Objective: This study aimed to test the hypothesis that phthalates disrupt placental hCG differentially in males and females with consequences for sexually dimorphic genital development. Design: The Infant Development and Environment Study (TIDES) is a prospective birth cohort. Pregnant women were enrolled from 2010–2012 at four university hospitals. Participants: Participants were TIDES subjects (n = 541) for whom genital and phthalate measurements were available and who underwent prenatal serum screening in the first or second trimester. Main Outcome Measures: Outcomes included hCG levels in maternal serum in the first and second trimesters and Anogenital Distance (AGD), which is the Distance from the anus to the genitals in male and female neonates. Results: Higher ...