NHANES epidemiological analysis of associations between exposure to perand polyfluoroalkyl substances (PFAS) and long-term amenorrhea in women of reproductive age Público

Abstract

Background: The per- and polyfluoroalkyl substances (PFAS) have been widely used in numerous consumer and industrial products. The high persistence of PFAS has led to extensive environmental contamination and bioaccumulation. Previous research revealed associations between exposure to PFAS and female reproductive disorders, but the underlying mechanisms remains elusive. Moreover, nearly all studies focused on perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the two long-chain legacy PFAS that have been gradually phased out, yet the reproductive impacts of other long-chain PFAS and short-chain alternatives are rarely studied.

Objectives: We aimed to use epidemiological approaches to investigate toxic effects of long- and short-chain PFAS on the female reproductive outcomes.

Methods: Using three consecutive 2-year cycles (2013-2018) of the National Health and Nutrition Examination Survey (NHANES) data, a cross-sectional analysis was performed to examine epidemiological associations between blood concentrations of PFAS and long-term amenorrhea in women of reproductive age, a proxy of ovarian dysfunction.

Results: The NHANES epidemiological analysis revealed that compared with menstruating women, women with long-term amenorrhea had significantly higher blood concentrations of several long-chain PFAS, including PFOA, PFOS, PFNA, PFHxS, and PFDeA. After the full adjustment for confounding factors, multiple logistic regression analysis revealed concentration-dependent associations between each of these long-chain PFAS and women’s long-term amenorrhea.

Discussion: This study utilizes epidemiological approaches to establish that exposure to long-chain PFAS at environmentally relevant levels presents a significant risk to women's reproductive health. emphasizing an urgent need to reduce or eliminate exposure to PFAS to protect women’s reproduction.

Keywords: Per- and polyfluoroalkyl substances, long-chain PFAS, short-chain PFAS, alternative, NHANES

Table of Contents

1. Abstract 2

2. Introduction 5

3. Materials and Methods 7

3.1 Study population 7

3.2 Measurements of blood (serum) concentrations of PFAS in NHANES participants and PFAS inclusion strategy 8

3.3 Subject inclusion 9

3.4 Definition of women with menstruation and long-term amenorrhea 9

3.5 Covariates selection 10

4. Data and statistical analysis 10

5. Results 11

6. Discussion 13

7. Conclusion 16

8. References 17

9. Appendices 22

9.1 Table 22

9.2 Figure legends 28

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Toxicology
Palavra-chave	Per- and polyfluoroalkyl substances alternative NHANES short-chain PFAS long-chain PFAS
Committee Chair / Thesis Advisor	Shah, Amit, Emory University

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