Skip to main content

Prenatal exposure to phthalates is associated with decreased anogenital distance and penile size in male newborns

  • L. P. Bustamante-Montes (a1), M. A. Hernández-Valero (a2), D. Flores-Pimentel (a3), M. García-Fábila (a4), A. Amaya-Chávez (a5), D. B. Barr (a6) and V. H. Borja-Aburto (a7)...

Reproductive effects from phthalate exposure have been documented mostly in animal studies. This study explored the association between prenatal exposure to phthalate metabolites, anogenital distance and penile measurements in male newborns in Toluca, State of Mexico. A total of 174 pregnant women provided urine samples for phthalate analysis during their last prenatal visit, and the 73 who gave birth to male infants were included in the study. The 73 male newborns were weighed and measured using standardized methods after delivery. After adjusting for creatinine and supine length at birth, significant inverse associations were observed between an index of prenatal exposure to total phthalate exposure and the distance from the anus to anterior base of the penis (β = −0.191 mm per 1 μg/l, P = 0.037), penile width (β = −0.0414, P = 0.050) and stretched length (β = −0.2137, P = 0.034); prenatal exposure to mono-2-ethylhexyl phthalate exposure was associated with a reduction in the stretched length of the penis (β = −0.2604, P = 0.050). Human exposure to phthalates is a public health concern, and the system most vulnerable to its potential effects seems to be the immature male reproductive tract.

Corresponding author
*Address for correspondence: Dr V. H. Borja-Aburto, Coordinación de Vigilancia Epidemiológica del Instituto Mexicano del Seguro Social (IMSS), Mier y Pesado no. 120 Col. del Valle, Deleg. Benito Juárez, C.P. 03100, México D.F., México. (Email
Hide All
1.Schettler T. Human exposure to phthalates via consumer products. Int J Androl. 2006; 29, 134139.
2.Wormut M. What are the sources of exposure to eight frequently used phthalic esters in Europeans? Risk Anal. 2006; 26, 803824.
3.Hoppin JA, Brock JW, Davis BJ, Baird DD. Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect. 2002; 110, 515518.
4.Hauser R, Meeker JD, Park S, Silva MJ, Calafat AM. Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environ Health Perspect. 2004; 112, 17341740.
5.Teitelbaum SL, Britton JA, Calafat AM, et al. Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. Environ Res. 2008; 106, 257269.
6.Masutomi N, Shibutani M, Takagi H, et al. Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life. Toxicology. 2002; 192, 149170.
7.Parks LG, Ostby JS, Lambright CR, et al. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci. 2000; 58, 339349.
8.Ema M, Miyawaki E. Adverse effects on development of the reproductive system in male offspring of rats given monobutyl phthalate, a metabolite of dibutyl phthalate during late pregnancy. Reprod Toxicol. 2001; 15, 189194.
9.Gray TJB, Beamand JA. Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells. Food Chem Toxicol. 1984; 22, 123131.
10.Nakahara H, Shono T, Suita S. Effects of prenatal exposure to phthalate ester on both testicular descent and urogenital development in rats. Fukuoka Igaku Zasshi. 2003; 94, 331337.
11.Swan SH, Main KM, Liu F, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005; 113, 10561061.
12.Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res. 2008; 108, 177184.
13.Suzuki Y, Yoshinaga J, Mizumoto Y, Serizawa S, Shiraishi H. Foetal exposure to phthalate esters and anogenital distance in male newborns. Intl J Androl. 2012; 35, 236244.
14.Huang PC, Kuo PL, Chou YY, Lin SJ, Lee CC. Association between prenatal exposure to phthalates and the health of newborns. Environ Int. 2009; 35, 1420.
15.Salazar-Martínez E, Romano-Riquer P, Yáñez-Márquez E, Longnecker MP, Hernandez-Avila M. Anogenital distance in human male and female newborns: a descriptive, cross-sectional study. Environ Health. 2005; 3, 813.
16.Capurro H, Konichezky S, Fonseca D, Caldeyro-Barcia R. A simplified method for diagnosis of gestational age in the newborn infant. J Pediatr. 1978; 93, 120122.
17.Albro PW, Jordan ST, Schroeder JL, Corbett JT. Chromatographic separation and quantitative determination of metabolites of di-(2 ethylhexyl)phthalate from urine of laboratory animals. J Chromatogr. 1982; 244, 6579.
18.Blount BC, Milgram KE, Silva MJ, et al. Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem. 2000; 72, 41274134.
19.García MA, Soberón E, Cortez M, Rodríguez R, Herrera JL. Métodos analíticos Guía de validación; Colegio Nacional de Químicos Farmacéuticos Biólogos A. C: México 2002.
20.Adibi JJ, Whyatt RM, Paige LW, et al. Characterization of phthalate exposure among pregnant women assessed by repeat air and urine samples. Environ Health Perspect. 2008; 116, 467473.
21.Svensson K, Hernández-Ramírez RU, Burguete-García A, et al. Phthalate exposure associated with self-reported diabetes among Mexican women. Environ Res. 2011; 111, 792796.
22.Romero-Franco M, Hernández-Ramírez RU, Calafat AM, et al. Personal care product use and urinary levels of phthalate metabolites in Mexican women. Environ Int. 2011; 37, 867871.
23.Romano-Riquer SP, Hernández-Ávila M, Gladen BC, Cupul-Uicab LA, Longnecker MP. Reliability and determinants of anogenital distance and penis dimensions in male newborns from Chiapas, Mexico. Paediatr Perinat Epidemiol. 2007; 21, 219228.
24.Fok TF, Hon KL, So HK, et al. The Hong Kong Neonatal Measurements Working Group. Normative data of penile length for term Chinese newborns. Biol Neonate. 2005; 87, 242245.
25.Anigstein CR. Longitud y diámetro del pene en niños de 0 a 14 años de edad. Arch Argent Pediatr. 2005; 103, 401405.
26.Damon V, Berlier P, Durozier B, Francois R. Study of the dimensions of the penis from birth to adult age and as a function of testicular volume. Pediatrie. 1990; 45, 519522.
27.Carmudan AD, Oz MO, Ilhan MN, et al. Current stretched penile length: cross-sectional study of 1040 healthy Turkish children aged 0 to 5 years. Urology. 2007; 70, 572575.
28.Al-Herbish AS. Standard penile size for normal full term newborns in the Saudi population. Saudi Med J. 2002; 23, 314316.
29.Fujieda K, Matsuura N. Growth and maturation in male genitalia from birth to adolescence II. Change of penile length. Pediatr Int. 1987; 29, 220223.
30.Lee PA, Mazur T, Danish R, et al. Micropenis I. Criteria, etiologies and classification. Johns Hopkins Med J. 1980; 146, 156163.
31.Anhalt H, Neely EK, Hintz RL. Ambiguous genitalia. Pediatr Rev. 1996; 17, 213220.
32.Mendiola J, Stahlnut RW, Jorgensen N, Liu F, Swan SH. Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ Health Pers. 2011; 119, 958963.
33.Bowman CJ, Barlow NJ, Turner KJ, Wallace DG, Foster PMD. Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rats. Toxicol Sci. 2003; 74, 393406.
34.Ge RS, Chen GR, Tanrikut C, Hardy MP. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod Toxicol. 2007; 23, 366373.
35.Chen GR, Dong L, Ge RS, Hardy MP. Relationship between phthalates and testicular dysgenesis syndrome. Zhonghua Nan Ke Xue. 2007; 13, 195200.
36.Welsh M, Saunders PTK, Fisken M, et al. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J Clin Invest. 2008; 118, 14791490.
37.World Health Organization (WHO). 2003. Healthy environments for children. Retrieved August 10, 2010, from
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 2
Total number of PDF views: 30 *
Loading metrics...

Abstract views

Total abstract views: 426 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st January 2018. This data will be updated every 24 hours.