Cohort Evidence Links Phthalate Exposure to Early Onset of Puberty in Chinese Girls

Girls' age of onset puberty has decreased globally in recent years. Emerging evidence suggests that exposure to phthalate esters (PAEs) could play a role in this trend. However, the relationship between PAE exposure and pubertal development in Chinese girls remains poorly understood. The present study aimed to address this issue by investigating the link between levels of urinary phthalate ester metabolites (mPAEs) and the risk of early puberty among 546 Chinese girls (6-8 years old) over a two-year monitoring program. Poisson regression, restricted cubic spline models, weighted quantile sum regression, and Bayesian kernel machine regression were used to assess both individual and combined effects of PAEs on pubertal development. Significant links were found between urinary concentrations of monoisobutyl phthalate (MiBP), monobutyl phthalate (MnBP), mono-(2-ethyl-5-oxohexyl) phthalate, the total of low molecular weight mPAEs, the total of nine commonly detected mPAEs, and the total of all mPAEs with the risk of early breast development (all P-trend < 0.05). Furthermore, levels of MnBP, MiBP, low molecular weight mPAEs, and mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with early menarche. Mixture effect analysis revealed incidence rate ratios of 1.64 (95% confidence interval (CI): 1.10-2.45) for early breast development and 2.33 (95% CI: 1.22-4.45) for early menarche. Short-chain mPAEs, particularly MiBP and MnBP, were identified as the major contributors to this combined effect. The present study demonstrated that exposure to PAEs, particularly short-chain PAEs, could lead to the early onset of puberty in Chinese girls.