Quantitative bias analysis of a reported association between perfluoroalkyl substances (PFAS) and endometriosis: The influence of oral contraceptive use

Oral contraceptive use as a determinant of plasma concentrations of perfluoroalkyl substances among women in the Norwegian Mother and Child Cohort (MoBa) study

“…Two studies have found higher PFAS concentrations in the blood of women with endometriosis compared with controls (30, 31). A study that applied physiologically-based pharmacokinetic (PBPK) models to data from the National Health and Nutrition Examination Survey reported that 13–16% of the association between endometriosis and blood PFAS concentrations might be explained by OC use (32), demonstrating the importance of considering OC use when examining the relationship between reproductive factors of PFAS blood concentrations.…”

From Environmental to Possible Occupational Exposure to Risk Factors: What Role Do They Play in the Etiology of Endometriosis?

“…The survey [47] on exposure to perfluoroalkyls suggests that these compounds may play a role in the onset of the disease, although the evidence of a single study, on 54 women with endometriosis, is not very indicative. Furthermore, regarding these compounds, some authors [84] suggested the role of oral contraceptives as confounding factors. However, what has been highlighted does not support the hypothesis of correlation between exposure to other types of pesticides, such as organophosphorus, pyrethroids and phenoxy herbicides [47], and endometriosis development, especially following the application of appropriate corrections for the confounding factors identified.…”

Predicting risks in an increasingly complex world

“…Two studies utilizing pharmacokinetic modeling have investigated whether the observed associations between PFOA exposure and early onset menopause or risk of endometriosis was due to reverse causation (Ngueta et al 2017;Ruark et al 2017). As discussed in Section 3.1.4, menstrual blood loss is a route of elimination of perfluoroalkyls.…”

“…As discussed in Section 3.1.4, menstrual blood loss is a route of elimination of perfluoroalkyls. Therefore, variability in menstruation such as menarche, menopause, and pharmacological management of menstruation (e.g., use of oral contraceptives) could affect serum perfluoroalkyl levels, and thereby contribute to observed statistical associations between serum PFOA levels and early onset menopause (Ruark et al 2017) or endometriosis (Ngueta et al 2017) outcomes.…”

“…Utilizing pharmacokinetic modeling, Ruark et al (2017) and Ngueta et al (2017) have investigated whether the observed associations between PFOS exposure and early onset menopause or risk of endometriosis was due to reverse causation. Menstrual blood loss is a route of elimination of perfluoroalkyls (see Section 3.1.4) and variability in menstruation such as menarche, menopause, and pharmacological management of menstruation (e.g., use of oral contraceptives) could affect serum perfluoroalkyl levels, and thereby contribute to observed statistical associations between serum PFOS levels and early onset menopause (Ruark et al 2017) or endometriosis (Ngueta et al 2017) outcomes.…”