Exposure to perfluorooctanoic acid and effects on reproductive hormones and pubertal onset in a longitudinal study of young girls

Abstract

Background: Perfluorooctanoic acid (PFOA), an endocrine disrupting chemical with worldwide exposure, causes changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing PFOA exposure but none have examined reproductive hormone levels. Methods: In a cohort of girls recruited at 6-8 years, clinical examinations were conducted annually or semi-annually with sequential Tanner staging. Serial serum samples were collected; PFOA concentration was measured in the first serum sample of 703 girls; estradiol, estrone (E1), testosterone (T) and dihydroandrostendione sufate (DHEA-S) were measured in serum of 205 Cincinnati girls at three time points around puberty. Relationships between PFOA, BMI, reproductive hormones, age at thelarche, pubarche and menarche were analyzed using linear regression, survival and structural equation (SEM) models. Results: Median serum concentrations in Cincinnati (N=352, 7.3 ng/mL) and the San Francisco Bay Area (N=351, 5.8 ng/mL) were higher than in the US population. In multivariable Cox proportional hazard models (adjusted for race, BMI), increasing serum log-transformed PFOA was associated with a delay in pubarche (HR 0.82, p=0.021) and menarche (HR 0.57). The effect on pubarche was more pronounced in lean girls (BMI%<67.3) (HR=0.745). PFOA also was inversely associated with DHEA-S (p=0.007), E1 (p= 0.027) and T (p=0.063) concentrations at six months prior to puberty. In SEMs of age at pubarche, PFOA had an inverse effect on endogenous variables E1 (p=0.019) and BMI (p=0.028). The effect of PFOA directly on age at pubarche also was an inverse association (p=0.003). With DHEA-S replacing E1, PFOA had similar inverse effects on BMI (p=0.026), DHEA-S (p=0.025) and age at pubarche (p=0.006). Conclusions: PFOA likely delays pubertal onset through the intervening effects on BMI and reproductive hormones. The decreases in DHEA-S and E1 associated with PFOA represent biological biomarkers of effect consistent with the delay in onset of puberty.