Associations between exposure to a mixture of perfluoroalkyl and polyfluoroalkyl substances and age at menarche in adolescent girls utilizing three statistical models

Abstract

Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS) is suggested to interfere with endocrine function and may affect female pubertal development. However, the epidemiological evidence on age at menarche associated with PFAS exposure is still inconsistent. Our objective was to investigate association of serum PFAS concentrations with age at menarche among 12-19 years old girls. We used data on 432 girls from National Health and Nutrition Examination Survey (NHANES) 2007-2012 cycles. NHANES reported serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) as quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS). Age at menarche was self-reported by girls or their guardians. Multivariable linear regression models were applied to estimate the association of individual PFAS exposure with age at menarche. The combined effects of PFAS mixture exposures on age at menarche were assessed using three statistical methods, including Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQS), and elastic net regression (ENR). In the single-chemical model, girls in the middle tertile of serum PFOA concentration had a lower age at menarche [regression coefficient (β) = -0.73 years, 95% confidence interval (CI): -1.44, -0.01; P = 0.047], compared with those in the lower tertile. Girls in the higher tertile of PFNA exposure were associated with older age at menarche (β = 0.36 years, 95% CI: 0.03, 0.80; P = 0.027), compared with those in the lower tertile. In the multiple-chemical models using BKMR and ENR approaches, higher PFNA exposure was significantly associated with older age at menarche among girls, after adjusting for other PFAS. We found suggestive evidence that higher PFAS mixture exposures may be related to an increase in age at menarche using the BKMR model. In conclusion, exposure to PFNA was associated with the later timing of menarche among girls.

Keywords: Age at menarche; Bayesian kernel machine regression (BKMR); Elastic net regression (ENR); Perfluoroalkyl and polyfluoroalkyl substances; Weighted quantile sum regression (WQS).