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3860773 
Journal Article 
Quantitative bias analysis of a reported association between perfluoroalkyl substances (PFAS) and endometriosis: The influence of oral contraceptive use 
Ngueta, G; Longnecker, MP; Yoon, M; Ruark, CD; Clewell, HJ; Andersen, ME; Verner, MA 
2017 
Yes 
Environment International
ISSN: 0160-4120
EISSN: 1873-6750 
104 
118-121 
English 
An association between serum levels of perfluoroalkyl substances (PFAS) and endometriosis has recently been reported in an epidemiologic study. Oral contraceptive use to treat dysmenorrhea (pelvic pain associated with endometriosis) could potentially influence this association by reducing menstrual fluid loss, a route of excretion for PFAS. In this study, we aimed to evaluate the influence of differential oral contraceptive use on the association between PFAS and endometriosis. We used a published life-stage physiologically based pharmacokinetic (PBPK) model to simulate plasma levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from birth to age at study participation (range 18-44years). In the simulated population, PFAS level distributions matched those for controls in the epidemiologic study. Prevalence and geometric mean duration (standard deviation [SD]) of oral contraceptive use in the simulated women were based on data from the National Health and Nutrition Examination Survey; among the women with endometriosis the values were, respectively, 29% and 6.8 (3.1) years; among those without endometriosis these values were 18% and 5.3 (2.8) years. In simulations, menstrual fluid loss (ml/cycle) in women taking oral contraceptives was assumed to be 56% of loss in non-users. We evaluated the association between simulated plasma PFAS concentration and endometriosis in the simulated population using logistic regression. Based on the simulations, the association between PFAS levels and endometriosis attributable to differential contraceptive use had an odds ratio (95% CI) of 1.05 (1.02, 1.07) for a loge unit increase in PFOA and 1.03 (1.02, 1.05) for PFOS. In comparison, the epidemiologic study reported odds ratios of 1.62 (0.99, 2.66) for PFOA and 1.25 (0.87, 1.80) for PFOS. Our results suggest that the influence of oral contraceptive use on the association between PFAS levels and endometriosis is relatively small. 
Quantitative bias assessment; Perfluoroalkyl substances (PFAS); Endometriosis; Physiologically based pharmacokinetic (PBPK) modeling; Oral contraceptive use; Environmental epidemiology; Biomarkers 
PFAS
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• ^Per- and Polyfluoroalkyl Substances (PFAS)
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     5:3 acid (914637-49-3)
          Literature Search
               Pubmed
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• PFNA
     Literature Search
          Toxline
     PFNA May 2019 Update
          Toxnet
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search – Adverse outcome pathway (2015-present)
          Pubmed
          WOS
     Screening Results
          Human/Epi studies
               Repro tox
     Literature Search Update (2013-2019)
          PubMed
          WOS