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Katharina M. Main,¹Gerda K. Mortensen,¹Marko M. Kaleva,² Kirsten A. Boisen,¹ Ida N. Damgaard,¹ Marla Chellakooty,¹ Ida M. Schmidt,¹ Anne-Maarit Suomi,² Helena E. Virtanen,² Jųrgen H. Petersen,^1,3 Anna-Maria Andersson,¹JormaToppari,^1,2 and Niels E. Skakkebęk¹

¹University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark; ²Departments of Physiology and Pediatrics, University of Turku, Turku, Finland; ³Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

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.

Key words: breast milk, exposure, human, infant, phthalate monoester, reproduction. Environ Health Perspect 114: 270-276 (2006) . doi:10.1289/ehp.8075 available via http://dx.doi.org/ [Online 7 September 2005]

Address correspondence to K.M. Main, University Department of Growth and Reproduction, Section 5064, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Telephone: 45 3545 5085. Fax: 45 3545 6054. E-mail: katharina.main@rh.hosp.dk

This study was supported by the European Commission (QLK4-CT-1999-01422 and QLK4-CT-2001-00269) , The Danish Medical Research Council (9700833, 9700909) , the Svend Andersen's and Velux Foundations, The Turku University Central Hospital, and the Academy of Finland. The sponsors had no part in study design, data collection, analysis, interpretation, or writing of the manuscript. The article does not represent the opinion of the European Commission, which is not responsible for any use that might be made of data appearing therein.

The authors declare they have no competing financial interests.

Received 2 March 2005 ; accepted 7 September 2005.

Correction

In Figure 1D of the original manuscript published online, the data for Finland and Denmark were reversed ; they have been corrected here.