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Cited by 696Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersSperm and Testicular Function

Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age

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Main, Katharina M., Mortensen, Gerda K., Kaleva, Marko M., Boisen, Kirsten A., Damgaard, Ida N., Chellakooty, Marla, Schmidt, Ida M., Suomi, Anne-Maarit +5 more·2006·Environmental Health Perspectives
DOI 10.1289/ehp.8075PMC PMC1367843
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Abstract

Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis. Design: We obtained biologic samples from a prospective Danish–Finnish cohort study on cryptorchidism from 1997 to 2001. We analyzed individual breast milk samples collected as additive aliquots 1–3 months postnatally (n = 130; 62 cryptorchid/68 healthy boys) for phthalate monoesters [mono-methyl phthalate (mMP), mono-ethyl phthalate (mEP), mono-n-butyl phthalate (mBP), mono-benzyl phthalate (mBzP), mono-2-ethylhexyl phthalate (mEHP), mono-isononyl phthalate (miNP)]. We analyzed serum samples (obtained in 74% of all boys) for gonadotropins, sex-hormone binding globulin (SHBG), testosterone, and inhibin B. Results: All phthalate monoesters were found in breast milk with large variations [medians (minimum–maximum)]: mMP 0.10 (< 0.01–5.53 μg/L), mEP 0.95 (0.07–41.4 μg/L), mBP 9.6 (0.6–10,900 μg/L), mBzP 1.2 (0.2–26 μg/L), mEHP 11 (1.5–1,410 μg/L), miNP 95 (27–469 μg/L). Finnish breast milk had higher concentrations of mBP, mBzP, mEHP, and Danish breast milk had higher values for miNP (p = 0.0001–0.056). No association was found between phthalate monoester levels and cryptorchidism. However, mEP and mBP showed positive correlations with SHBG (r = 0.323, p = 0.002 and r = 0.272, p = 0.01, respectively); mMP, mEP, and mBP with LH:free testosterone ratio (r = 0.21–0.323, p = 0.002–0.044) and miNP with luteinizing hormone (r = 0.243, p = 0.019). mBP was negatively correlated with free testosterone (r = −0.22, p = 0.033). Other phthalate monoesters showed similar but nonsignificant tendencies. Conclusions: Our data on reproductive hormone profiles and phthalate exposures in newborn boys are in accordance with rodent data and suggest that human Leydig cell development and function may also be vulnerable to perinatal exposure to some phthalates. Our findings are also in line with other recent human data showing incomplete virilization in infant boys exposed to phthalates prenatally.

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  • MiNP was the major metabolite found in breast milk collected from mothers in Denmark (101 μg/L) and Finland (89 μg/L).

    “MiNP was the major metabolite found in breast milk collected from mothers in Denmark (101 µg/L) and Finland (89 µg/L) [25,159].”

    From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [25]

    The Results state that miNP had the highest concentration of the measured phthalate monoesters in breast milk and that levels were higher in Denmark than Finland. Our copy gives a pooled median of 95 µg/L in the Abstract > Results, but the passages do not provide the claimed country-specific values of 101 and 89 µg/L. (LLM, conf=0.82)

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Authors
Main, K. M., Mortensen, G. K., Kaleva, M. M., Boisen, K. A., Damgaard, I. N., Chellakooty, M., Schmidt, I. M., Suomi, A.-M., Virtanen, H. E., Petersen, J. H., Andersson, A.-M., Toppari, J., & Skakkebæk, N. E.
Affiliations
  • Rigshospitalet (DK)
  • University of Turku (FI)
  • University of Copenhagen (DK)
ORCID
Venue
Environmental Health Perspectives
Publisher
American Chemical Society (ACS)
Published
2005-09-07
Volume
114
Issue
2
Pages
270-276
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
DOI
10.1289/ehp.8075
PMC
PMC1367843
OpenAlex
W1993833615
Cited by
696
References
1
Citations by year
2026: 11 · 2025: 15 · 2024: 20 · 2023: 25 · 2022: 31 · 2021: 35 · 2020: 27 · 2019: 29 · 2018: 46 · 2017: 36 · 2016: 29 · 2015: 32 · 2014: 40 · 2013: 39 · 2012: 46
FWCI
24.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
phthalates, phthalate monoesters, breast milk contamination, cryptorchidism, testicular dysgenesis, sex hormone-binding globulin, luteinizing hormone, free testosterone, inhibin B, gonadotropins, mono-n-butyl phthalate
MeSH terms
Adult, Cryptorchidism, Denmark, Female, Finland, Humans, Infant, Newborn, Longitudinal Studies, Male, Milk, Human, Phthalic Acids, Pregnancy, Prenatal Exposure Delayed Effects, Gonadal Steroid Hormones, Cohort Studies

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