title: Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age.
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.
  
  
  METHODS
  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 microg/L), mEP 0.95 (0.07-41.4 microg/L), mBP 9.6 (0.6-10,900 microg/L), mBzP 1.2 (0.2-26 microg/L), mEHP 11 (1.5-1,410 microg/L), miNP 95 (27-469 microg/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.
authors.affiliation: University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. katharina.main@rh.hosp.dk
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
authors.forename: Gerda K
authors.initials: GK
authors.lastname: Mortensen
authors.forename: Marko M
authors.initials: MM
authors.lastname: Kaleva
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Boisen
authors.forename: Ida N
authors.initials: IN
authors.lastname: Damgaard
authors.forename: Marla
authors.initials: M
authors.lastname: Chellakooty
authors.forename: Ida M
authors.initials: IM
authors.lastname: Schmidt
authors.forename: Anne-Maarit
authors.initials: AM
authors.lastname: Suomi
authors.forename: Helena E
authors.initials: HE
authors.lastname: Virtanen
authors.forename: Dajørgen Vid H
authors.initials: DV
authors.lastname: Petersen
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Andersson
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.forename: Niels E
authors.initials: NE
authors.lastname: Skakkebaek
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003456:Cryptorchidism / Q000139:chemically induced*; D003718:Denmark; D005260:Female; D005387:Finland; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D010795:Phthalic Acids / Q000032:analysis / Q000506:poisoning*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D012739:Gonadal Steroid Hormones; D010795:Phthalic Acids