title: Perfluorooctanoic acid exposure and natural menopause: A longitudinal study in a community cohort.
abstract: BACKGROUND
  Perfluorooctanoic acid (PFOA), a suspected endocrine disruptor, is a bio-persistent chemical found at low levels in the serum of nearly all U.S. residents. Early menopause has been positively associated with serum PFOA in prior cross-sectional studies.
  
  
  METHODS
  We conducted a longitudinal analysis of age at menopause among women, aged ≥40 years, (N=8759) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels via contaminated drinking water. Using estimated retrospective year-specific serum PFOA concentrations (1951-2011), we examined the associations between PFOA, as cumulative exposure or year-specific serum estimates, and natural menopause using a Cox proportional hazards models. As participants were initially recruited in 2005-2006, we also analyzed the cohort prospectively (i.e., from the time of enrollment), using both modeled cumulative PFOA, and PFOA serum levels measured in 2005-2006. Women with hysterectomy (a competing risk) were either censored or excluded from the analysis.
  
  
  RESULTS
  Neither in the retrospective nor the prospective cohort did we find a significant (at α=0.05) trend between PFOA exposure and natural menopause. The non-significant, hazard ratios by quintile of increasing cumulative serum PFOA were 1.00 (referent), 1.00, 1.09, 1.05 and 1.06 (trend test for log cumulative exposure: p=0.37) with hysterectomies censored, and 1.00 (referent), 1.06, 1.13, 1.09 and 1.11 (trend test for log cumulative exposure: p=0.85) with hysterectomies excluded. Year-specific serum estimates were also not associated with early menopause.
  
  
  CONCLUSIONS
  Our data suggest that earlier age at menopause is not associated with PFOA exposure.
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA. Electronic address: rdhingra@emory.edu.
authors.forename: Radhika
authors.initials: R
authors.lastname: Dhingra
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA. Electronic address: ldarrow@emory.edu.
authors.forename: Lyndsey A
authors.initials: LA
authors.lastname: Darrow
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA. Electronic address: mklein@emory.edu.
authors.forename: Mitch
authors.initials: M
authors.lastname: Klein
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA. Electronic address: awinqui@emory.edu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Winquist
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA. Electronic address: nsteenl@emory.edu.
authors.forename: Kyle
authors.initials: K
authors.lastname: Steenland
mesh_terms: D000328:Adult; D017677:Age Distribution; D002210:Caprylates / Q000097:blood / Q000633:toxicity*; D015331:Cohort Studies; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000633:toxicity*; D006801:Humans; D008137:Longitudinal Studies; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D008954:Models, Biological; D009820:Ohio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D014903:West Virginia
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; C023036:perfluorooctanoic acid