title: Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study.
abstract: OBJECTIVE
  Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity?
  
  
  CONCLUSIONS
  The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure.
  
  
  BACKGROUND
  PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent.
  
  
  METHODS
  A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine.
  
  
  METHODS
  Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: ≤24 days, long cycle: ≥32 days) and irregularities (≥7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95% confidence intervals (CIs).
  
  
  RESULTS
  Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95% CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95% CI: 0.8; 3.5)]. The overall response rate was 45.3% with considerable variation between countries (91.3% in Greenland, 69.1% in Poland and 26.3% in Ukraine).
  
  
  CONCLUSIONS
  Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded.
  
  
  CONCLUSIONS
  The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA.
  
  
  BACKGROUND
  Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), www.inuendo.dk. The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study (www.inuendo.dk/clear) supported by the European Commission's 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.
authors.affiliation: Department of Occupational Medicine, Danish Ramazzini Centre, Aarhus University Hospital, Noerrebrogade 44, build. 2C, DK-8000 Aarhus C, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Lyngsø
authors.forename: C H
authors.initials: CH
authors.lastname: Ramlau-Hansen
authors.forename: B B
authors.initials: BB
authors.lastname: Høyer
authors.forename: H
authors.initials: H
authors.lastname: Støvring
authors.forename: J P
authors.initials: JP
authors.lastname: Bonde
authors.forename: B A G
authors.initials: BA
authors.lastname: Jönsson
authors.forename: C H
authors.initials: CH
authors.lastname: Lindh
authors.forename: H S
authors.initials: HS
authors.lastname: Pedersen
authors.forename: J K
authors.initials: JK
authors.lastname: Ludwicki
authors.forename: V
authors.initials: V
authors.lastname: Zviezdai
authors.forename: G
authors.initials: G
authors.lastname: Toft
mesh_terms: D017738:Alkanesulfonic Acids / Q000009:adverse effects*; D015992:Body Mass Index; D002210:Caprylates / Q000009:adverse effects*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005466:Fluorocarbons / Q000009:adverse effects*; D006116:Greenland; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects*; D008599:Menstruation Disturbances / Q000209:etiology*; D011044:Poland; D011295:Prenatal Care; D012044:Regression Analysis; D012907:Smoking; D011795:Surveys and Questionnaires; D014455:Ukraine
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid
keywords: PFOA; PFOS; menstrual cycle