title: Female exposure to phthalates and time to pregnancy: a first pregnancy planner study.
abstract: Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)?
  
  
  
  Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP.
  
  
  
  Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction.
  
  
  
  A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort.
  
  
  
  We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol.
  
  
  
  Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP.
  
  
  
  Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began.
  
  
  
  Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products.
  
  
  
  The original data collected were founded by Aarhus University Research Foundation, the Danish Medical Research Council and the Danish Medical Health Insurance Foundation. There are no conflicts of interest to be declared.
  
  
  
  N/A.
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Anne Marie L
authors.initials: AM
authors.lastname: Thomsen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Riis
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University Hospital, SE 221 85 Lund, Sweden.
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University Hospital, SE 221 85 Lund, Sweden.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Lindh
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.|Department of Occupational Medicine, Herning Regional Hospital, DK-7400 Herning, Denmark.
authors.forename: Niels H
authors.initials: NH
authors.lastname: Hjollund
authors.affiliation: Department of Environmental Medicine, University of Southern Denmark, DK-5000 Odense, Denmark.
authors.forename: Tina Kold
authors.initials: TK
authors.lastname: Jensen
authors.affiliation: Department of Occupational and Environmental Medicine, Copenhagen University Hospital Bispebjerg-Frederiksberg, DK-2400 Copenhagen NW, Denmark.
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Bonde
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark gunnar.toft@clin.au.dk.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
mesh_terms: D000328:Adult; D004781:Environmental Exposure; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D010795:Phthalic Acids / Q000633:toxicity* / Q000652:urine; D011247:Pregnancy; D061685:Time-to-Pregnancy / Q000187:drug effects*; D055815:Young Adult
chemical_list: D010795:Phthalic Acids; C581825:monoethyl phthalate; C028577:monobutyl phthalate
keywords: MEP; fecundity; fertility; phthalates; time to pregnancy