Shorter Anogenital Distance Predicts Poorer Semen Quality in Young Men in Rochester, New York

Department of Obstetrics and Gynecology, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 03/2011; 119(7):958-63. DOI: 10.1289/ehp.1103421
Source: PubMed


In male rodents, anogenital distance (AGD) provides a sensitive and continuous correlate of androgen exposure in the intrauterine environment and predicts later reproductive success. Some endocrine-disrupting chemicals can alter male reproductive tract development, including shortening AGD, in both rodents and humans. Whether AGD is related to semen quality in human is unknown.
We examined associations between AGD and semen parameters in adult males.
We used multiple regression analyses to model the relationships between sperm parameters and two alternative measures of AGD [from the anus to the posterior base of the scrotum (AGD(AS)) and to the cephalad insertion of the penis (AGD(AP))] in 126 volunteers in Rochester, New York.
AGD(AS), but not AGD(AP), was associated with sperm concentration, motility, morphology, total sperm count, and total motile count (p-values, 0.002-0.048). Men with AGD(AS) below (vs. above) the median were 7.3 times more likely (95% confidence interval, 2.5-21.6) to have a low sperm concentration (< 20 × 10⁶/mL). For a typical study participant, sperm concentrations were 34.7 × 10⁶/mL and 51.6 × 10⁶/mL at the 25th and 75th percentiles of (adjusted) AGD(AS).
In our population, AGD(AS) was a strong correlate of all semen parameters and a predictor of low sperm concentration. In animals, male AGD at birth reflects androgen levels during the masculinization programming window and predicts adult AGD and reproductive function. Our results suggest, therefore, that the androgenic environment during early fetal life exerts a fundamental influence on both AGD and adult sperm counts in humans, as demonstrated in rodents.

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    • "In 2005, Swan et al., reported for relationship between phthalates and reduced anogenital distance in baby boys. Mendiola et al., 2011 determined the association of phthalates exposure with reduced sperm in young men. Swan et al., 2005 reported that the babies of mothers exposed to high levels of four phthalate metabolites -MI, MBzP, MEP and MiBP, have lower anogenital index and is more likely to have small genitals and partially no descended testes (Swan et al., 2005). "
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    ABSTRACT: A number of reports published worldwide create awareness on the harms of global usage of phthalates in various products. The concern towards potential exposure of consumers to phthalates through many sources and different routes of administration is increasing day by day. Evidences of phthalates in toys and phthalate metabolites in the urine of children are becoming common. Children under 3 years are more sensitive as compared to general population towards this problem due to their additional intake of plasticizers by chewing toys. Phthalates are found to cause allergy, asthma and affecting kidney, liver and endocrine system, especially at a young age. As phthalates bear the property to soften the hard plastic material, soft toys possess their higher content in comparison to hard toys. Their usage is restricted in EU, United States and Canada and several other countries mainly in toys suspected to be kept in mouth. Phthalates basically included in the banned for toys category are DEHP, DBP, BBP, DNOP, DIDP and DINP. Usage of less than 0.1% phthalates has been allowed for plastic toys and directives are given to producers to label the age of children who may use the toys and specify its hazards. Parents are suggested to control these labels before buying the phthalate plasticizers based products.
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    • "In males, children with hypospadias and cryptorchidism have significantly shorter AGD than controls (Hsieh et al., 2008, 2012; Thankamony et al., 2013). In male adults, shorter AGD predicts poorer semen quality (Eisenberg et al., 2011; Mendiola et al., 2011) and reduced testosterone and testicular volume (Eisenberg et al., 2012). Among men seen in an infertility clinic, AGD was longer in fathers than in infertile men (Eisenberg et al., 2011). "
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    ABSTRACT: Is first trimester phthalate exposure associated with anogenital distance (AGD), a biomarker of prenatal androgen exposure, in newborns? Concentrations of diethylhexyl phthalate (DEHP) metabolites in first trimester maternal urine samples are inversely associated with AGD in male, but not female, newborns. AGD is a sexually dimorphic measure reflecting prenatal androgen exposure. Prenatal phthalate exposure has been associated with shorter male AGD in multiple animal studies. Prior human studies, which have been limited by small sample size and imprecise timing of exposure and/or outcome, have reported conflicting results. The Infant Development and the Environment Study (TIDES) is a prospective cohort study of pregnant women recruited in prenatal clinics in San Francisco, CA, Minneapolis, MN, Rochester, NY and Seattle, WA in 2010-2012. Participants delivered 787 infants; 753 with complete data are included in this analysis. Any woman over 18 years old who was able to read and write English (or Spanish in CA), who was <13 weeks pregnant, whose pregnancy was not medically threatened and who planned to deliver in a study hospital was eligible to participate. Analyses include all infants whose mothers provided a first trimester urine sample and who were examined at or shortly after birth. Specific gravity (SpG) adjusted concentrations of phthalate metabolites in first trimester urine samples were examined in relation to genital measurements. In boys (N = 366), we obtained two measures of anogenital distance (AGD) (anoscrotal distance, or AGDAS and anopenile distance, AGDAP) as well as penile width (PW). In girls (N = 373), we measured anofourchette distance (AGDAF) and anoclitoral distance (AGDAC). We used multivariable regression models that adjusted for the infant's age at exam, gestational age, weight-for-length Z-score, time of day of urine collection, maternal age and study center. Three metabolites of DEHP were significantly and inversely associated with both measures of boys' AGD. Associations (β, 95% confidence interval (CI)) between AGDAS and (log10) SpG-adjusted phthalate concentrations were: -1.12 (-2.16, -0.07) for mono-2-ethylhexyl phthalate (MEHP), -1.43, (-2.49, -0.38) for mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and -1.28 (-2.29, -0.27) for mono-2-ethyl-5-hydroxyhexyl (MEHHP). Associations were of similar magnitude for AGDAP. Associations were weaker and not statistically significant for PW. No other phthalate metabolites were associated with any genital measurement in boys. No phthalate metabolites were associated with either AGD measure in girls. Exposure assessment was based on a single first trimester urine sample, which may have introduced exposure misclassification. In addition, significant between-center differences suggest that this measurement is difficult to standardize. Our findings are consistent with multiple rodent studies and most human studies which were far smaller. The data we report here suggest that even at current low levels, environmental exposure to DEHP can adversely affect male genital development resulting in reproductive tract changes that may impact reproductive health later in life. These findings have important implications for public policy since most pregnant women are exposed to this ubiquitous chemical. Funding for TIDES was provided by the following grants from the National Institute of Environmental Health Sciences: R01ES016863-04 and R01 ES016863-02S4. The authors report no conflict of interest. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
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    • "While long-term studies of perinatal exposure to BPA and adult reproductive health are lacking, prenatal BPA exposure has been correlated with reduced anogenital distance (AGD) in babies (Li et al., 2011). Importantly, AGD is positively associated with semen quality in adulthood, which suggests that developmental exposure to BPA in humans may result in decreased semen quality in adulthood (Mendiola et al., 2011). "
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    General and Comparative Endocrinology 09/2014; 214. DOI:10.1016/j.ygcen.2014.09.014 · 2.47 Impact Factor
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