Exposure to Perfluoroalkyl Substances and Associations with Pubertal Onset and Serum Reproductive Hormones in a Longitudinal Study of Young Girls in Greater Cincinnati and the San Francisco Bay Area

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS), endocrine disrupting chemicals with worldwide exposure, cause changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing perfluorooctanoic acid (PFOA) exposure, but to our knowledge none have examined reproductive hormone levels at thelarche. Methods: In a cohort of Greater Cincinnati (GC) and San Francisco Bay Area (SFBA) girls recruited at 6–8 years of age, clinical examinations were conducted annually or semiannually with sequential Tanner staging. PFAS concentrations were measured in the first serum sample of 704 girls. In 304 GC girls, estradiol ( ), estrone ( ), testosterone (T), and dihydroepiandrosterone sulfate (DHEAS) were measured in serum at four time points around puberty. Relationships between PFAS and age at thelarche, pubarche, and menarche were analyzed using survival and structural equation models. The association between PFAS and reproductive hormones was assessed using linear regression models. Results: Median PFOA serum concentrations in GC ( , ) and the SFBA ( , ) were higher than in the U.S. population. In multivariable Cox proportional hazard models [adjusted for race, body mass index (BMI)], increasing serum log-transformed PFOA was associated with a delay in pubarche [ ; 95% CI: 0.70, 0.99] and menarche ( ; 95% CI: 0.01, 0.25). Structural equation models indicated a triangular relationship between PFOA, BMI percentile, and the age at the pubertal milestone. Increased PFOA had a statistically significant direct effect of delay on all three milestones, as did BMI. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and 2-( -methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) also were associated with later thelarche, and Me-PFOSA-AcOH also with later pubarche. PFOA was inversely associated with DHEAS ( ), ( ), and T ( ) concentrations at 6 months prior to puberty. Conclusions: PFAS may delay pubertal onset through the intervening effects on BMI and reproductive hormones. The decreases in DHEAS and associated with PFOA represent biological biomarkers of effect consistent with the delay in onset of puberty. https://doi.org/10.1289/EHP11811

Invited Perspective: PFAS and Pubertal Timing in Girls—A Maturing Literature

“…In this issue, Pinney et al. 15 overcome limitations and advance the field through a carefully and intentionally designed longitudinal study developed as part of the larger Breast Cancer and the Environmental Research Program. 16 , 17 PFAS were measured in middle childhood (6–8 years of age) reducing concerns regarding “late age at entry” that have hindered prior studies.…”