Association of blood metal exposure with age at menarche in Korean women: KNHANES (2008-2017)

Humans are exposed to metals in their daily lives and this metal exposure is responsible for various adverse health effects. Delayed pubertal development has been suggested as an adverse outcome of metal exposure; however, evidence in nationally representative populations, especially in Asia, is limited. We evaluated the association of blood cadmium (Cd), lead (Pb), and mercury (Hg) levels with the age at menarche in Korean females whose blood heavy metals were measured as part of the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2017. Among the females 16 years of age or older, all measured heavy metals in blood, i.e., Cd, Pb, and Hg, were positively associated with age at menarche. These associations remained significant in a model adjusted for age, survey year, income, education, body mass index, smoking history, and menopausal status as covariates (beta: 0.10, 95% confidence interval (CI): 0.03-0.18 for Cd; beta: 0.17, 95%CI: 0.06-0.27 for Pb; beta: 0.12, 95%CI: 0.05-0.19 for Hg). When the population was separated by age group at the time of the survey, the significance between heavy metal levels and age at menarche became inconsistent, but the general trends were similar. Among those in their 20s and 40s, blood Cd showed a significant association, while Pb was significant among those in their 40s and 50s. A similar trend was observed in the sensitivity analysis in the girls aged 10-15 years at the time of the survey. Blood Cd levels were associated with decreased odds of precocious menarche (OR: 0.57, 95%CI: 0.31-1.03). Delayed menarche is a risk factor for cardiovascular and chronic kidney diseases in later life; hence, public health implication of heavy metal exposure warrants a public health attention.