US EPA

3981395 

Journal Article 

Quantitative bias analysis for epidemiological associations of perfluoroalkyl substance serum concentrations and early onset of menopause 

Ruark, CD; Song, G; Yoon, M; Verner, MA; Andersen, ME; Clewell, HJ; Longnecker, MP 

2017 

1 

Environment International
ISSN: 0160-4120
EISSN: 1873-6750 

PERGAMON-ELSEVIER SCIENCE LTD 

OXFORD 

99 

245-254 

English 

27927583 

10.1016/j.envint.2016.11.030 

WOS:000394062700024 

https://linkinghub.elsevier.com/retrieve/pii/S0160412016309205
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An association between increased serum concentrations of perfluoroalkyl substances (PFAS) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and early menopause has been reported (Knox et al., 2011; Taylor et al., 2014). This association may be explained by the fact that women who underwent menopause no longer excrete PFAS through menstruation. Our objective was to assess how much of the epidemiologic association between PFAS and altered timing of menopause might be explained by reverse causality. We extended a published population life-stage physiologically-based pharmacokinetic (PBPK) model of PFOS and PFOA characterized by realistic distributions of physiological parameters including age at menopause. We then conducted Monte Carlo simulations to replicate the Taylor population (Taylor et al., 2014) and the Knox population (Knox et al., 2011). The analysis of the simulated data overall showed a pattern of results that was comparable to those reported in epidemiological studies. For example, in the simulated Knox population (ages 42-51) the odds ratio (OR) for menopause in the fifth quintile of PFOA compared to those in the first quintile was 1.33 (95% CI 1.26-1.40), whereas the reported OR was 1.4 (95% CI 1.1-1.8). Using our model structure, a substantial portion of the associations reported can be explained by pharmacokinetics. 

Quantitative bias analysis; Menopause