title: The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence: a pilot study.
abstract: We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and polycystic ovarian morphology (PCO) in adolescence. The Western Australian Pregnancy Cohort (Raine) Study recruited 3000 women at 18 weeks of gestation in 1989-1991, 1377 had antenatal serum stored without thawing at -80 °C. An unselected subset was evaluated in the early follicular phase for PCO and PCOS by ultrasound and serum evaluation in adolescence. Serum was analysed for anti-Müllerian hormone (AMH), inhibin B, sex hormone binding globulin (SHBG), testosterone, androstenedione and DHEAS. Four hundred microlitres of the frozen maternal serum underwent isotope-diluted liquid chromatography-tandem mass spectrometry, with preceding enzymatic deconjugation followed by solid-phase extraction to determine phthalate exposure. Two hundred and forty four girls attended assessment and most common phthalate metabolites were detectable in the majority of the 123 samples available. Several phthalates were negatively associated with maternal SHBG, and associations with maternal androgens were less consistent. The sum of the metabolites of di-(2-ethylhexyl) phthalate was associated with a non-significant tendency towards an earlier age at menarche (P=0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl) phthalate (P=0.018). Exposure to monoethyl phthalate (MEP) and the sum of all phthalate metabolites (Σall phth.m) were protective against PCOS in adolescence (P=0.001 and P=0.005 respectively). There were negative associations of MEP with PCO (P=0.022) and of MEP with serum AMH (P=0.031). Consequently, our data suggest that antenatal exposure to environmental phthalates may be associated with oestrogenic and/or anti-androgenic reproductive effects in adolescent girls.
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, Perth, Western Australia 6008, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Hart
authors.forename: Dorota A
authors.initials: DA
authors.lastname: Doherty
authors.forename: Hanne
authors.initials: H
authors.lastname: Frederiksen
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Keelan
authors.forename: Martha
authors.initials: M
authors.lastname: Hickey
authors.forename: Deborah
authors.initials: D
authors.lastname: Sloboda
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Niels E
authors.initials: NE
authors.lastname: Skakkebaek
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Main
mesh_terms: D000293:Adolescent; D041923:Adolescent Development / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D010795:Phthalic Acids / Q000097:blood / Q000494:pharmacology*; D010865:Pilot Projects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000503:physiopathology*; D011627:Puberty / Q000187:drug effects*; D012098:Reproduction / Q000187:drug effects*
chemical_list: D010795:Phthalic Acids