The association between PFAS exposure, menstrual cycle parameters, and reproductive hormones in adolescent girls

CONTEXT: Perfluoroalkyl and polyfluoroalkyl substances (PFAS), sometimes referred to as "forever chemicals", are widespread. Certain PFAS exposures have been associated with reproductive abnormalities in women but limited data exist in adolescents. OBJECTIVE: To investigate the relationship between PFAS, menstrual cycle length/variability, and reproductive hormones in adolescents. METHODS: Thirty-eight girls completed menstrual diaries and contributed daily urine samples to measure creatinine (Cr)-corrected luteinizing hormone (LH), estrone-3-glucuronide (E1G), and pregnanediol-3-glucuronide (PdG). Twenty-four PFAS were measured (n=88 serum samples, average 2.32 samples/participant over the course of 1.20 ± 1.34 years) using mass spectrometry. Linear mixed effects models were used to assess associations between PFAS and total cycle, follicular phase, and luteal phase lengths and hormone levels. Models were performed unadjusted and adjusted for gynecologic age, body fat percent, and race/ethnicity. RESULTS: Participants were 12.8 ± 1.0 years old (mean ± SD) with a gynecologic age of 0.3 ± 0.2 years. Most were non-Hispanic White and of normal weight. Four PFAS were consistently detected: perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS). There were no associations between PFAS and cycle length or variability. PFBS was positively associated with peak E1G levels (β = 0.15, 95% CI [0.00, 0.29], p=0.049), but no species was associated with peak LH or PdG levels. CONCLUSION: PFAS were widely detected in healthy girls. PFBS was positively associated with E1G levels, suggesting potential ovarian effects. Analyses are ongoing to understand PFAS exposure sources and to determine if ongoing exposure may impact reproductive health.