Associations of perfluorooctanoic acid with menopause and chronic kidney disease Public
Dhingra, Radhika (2015)
Published
Abstract
In this dissertation I investigated the associations of perflurooctanoic acid (PFOA) with menopause and chronic kidney disease (CKD) in a mid-Ohio Valley community cohort (N=32,254), subjected to a wide range of PFOA exposures via drinking water since 1951. Persistent in the environment and the human body, PFOA is found at low concentrations in the serum of nearly all U.S. residents. Earlier menopause and CKD have been positively associated with increased serum PFOA in previous cross-sectional studies.
Using Cox proportional hazards models, I conducted longitudinal analyses of menopause among women, aged 40 years or greater, (N=8,759) and of chronic kidney disease (CKD) among adults, aged 20 years or greater (N=32,254). In prior work, year-specific serum PFOA concentrations (1951-2011) in this population were retrospectively modeled, independently of measured PFOA. Estimated glomerular filtration rate (eGFR; a marker of kidney function) and serum PFOA level were measured in blood samples collected at enrollment (2005/2006). Individual self-reported histories of menopause and CKD were collected in 2008-2011, and self-reported CKD was validated via medical records or the US Renal Data System registry. I retrospectively investigated associations of menopause and of CKD with modeled PFOA exposure, either using year-specific estimates or estimated cumulative PFOA exposure. For both outcomes, I prospectively analyzed cohort members who had not yet experienced the outcome at enrollment. Using cross-sectional analyses to assess possible reverse causation, I evaluated the associations of measured and modeled serum PFOA with menopause among women aged 30-65, and with eGFR among adults. I also assessed the impact of the number of years since menopause on measured serum PFOA concentrations.
In longitudinal analyses, neither menopause nor CKD were associated with exposure to cumulative or year-specific PFOA estimates. Measured serum PFOA was positively associated with both menopause and eGFR (trend tests p=0.0005 and p=0.013, respectively), while modeled serum PFOA was not. Measured serum PFOA concentrations appeared to increase for the first seven years after menopause (trend test, p<0.0001). These results suggest that earlier menopause and CKD are not caused by PFOA exposure, and that positive findings in previous cross-sectional studies may have been the result of reverse causation.
Table of Contents
Chapter 1:
Introduction_____________________________________1
Perfluorooctanoic acid (PFOA or
C8)__________________________________1
The mid-Ohio Valley cohort and the strength of its data__________________ 2
Prior findings in the literature: Menopause and CKD_____________________ 5
Study design of papers 1 and 2_____________________________________ 7
Reverse causation and serum biomarkers of chemical exposure ____________ 10
Study design of paper 3___________________________________________ 13
References_____________________________________________________15
Chapter 2:
Perfluorooctanoic acid exposure and natural
menopause:
a longitudinal study in a community
cohort_____________________25
Abstract_______________________________________________________26
Introduction____________________________________________________27
Methods_______________________________________________________29
Cohort recruitment &
survey_______________________________________
29
Serum PFOA concentrations: measured and
modeled____________________
31
Data
analysis___________________________________________________
32
Results________________________________________________________36
Cohort characteristics & hysterectomy survival analysis results____________ 36
Menopause survival analysis results_________________________________ 36
Discussion_____________________________________________________38
Conclusion_____________________________________________________41
References_____________________________________________________42
Tables and Figures _______________________________________________ 50
Appendix Tables and Figures _______________________________________ 57
Chapter 3:
Perfluorooctanoic acid and chronic kidney
disease:
longitudinalanalysis of a Mid-Ohio
Valley
community______________61
Abstract________________________________________________________62
Introduction_____________________________________________________63
Methods________________________________________________________66
Study cohort & survey
data_________________________________________
66
Case definition and cohort
construction________________________________
67
Modeled PFOA
exposure____________________________________________
69
Data
analyses____________________________________________________
70
Results_________________________________________________________72
Cohort characteristics______________________________________________ 72
Survival analysis: Cumulative PFOA
exposure___________________________
72
Survival analysis: Serum PFOA
estimates______________________________
73
Discussion______________________________________________________73
Conclusion______________________________________________________76
References______________________________________________________77
Tables and Figures ________________________________________________ 84
Appendix Tables __________________________________________________ 89
Chapter 4:
A study of reverse causation: Examining the
associations of
perfluorooctanoic acid serum levels with two
outcomes_____________91
Abstract_________________________________________________________92
Introduction______________________________________________________94
Methods_________________________________________________________98
Data: Surveys, PFOA and
eGFR_______________________________________
99
Analyses: eGFR and PFOA in
adults____________________________________
100
Analyses: Menopause and
PFOA_______________________________________
101
Results___________________________________________________________103
eGFR
analyses_____________________________________________________
103
Menopause
analyses________________________________________________
104
Discussion________________________________________________________105
Conclusions_______________________________________________________109
References________________________________________________________112
Tables and Figures __________________________________________________ 119
Chapter 5: Summary and Conclusion_____________________________129
References________________________________________________________133
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