Lead (Pb), mercury (Hg), and cadmium (Cd) are non-essential metals that have been associated with a range of health problems (Singh et al., 2011). Metal exposure has been reported to contribute to cardiovascular diseases (Nguyen et al., 2021), thyroid dysfunction (Chung et al., 2019), and metabolic syndrome (Moon, 2014). Furthermore, heavy metals may disrupt endocrine functions and impair reproductive health (Iavicoli et al., 2009).

In females, physical maturation and onset of menarche represent critical phenotypic changes marking the development of reproductive capacity during puberty. Delayed puberty is defined as the absence of secondary sex characteristics until 13 years of age or the absence of menarche until 15 years of age (KSOG, 2021).

Various factors influence the timing of puberty, and these include genetics, health, nutritional status, obesity, socioeconomic status, geological factors, and environmental exposure (Biro et al., 2012; Boswell, 2014). The average age at menarche differs by ethnicity, as reported in the United States (Anderson and Must, 2005): For the Caucasian population, premature onset of menarche is defined as the first menstruation at the age of 7, while for the black population, at the age of 6 (KSOG, 2021). The average age at menarche also varies by region and by generation (KSOG, 2021). A higher body mass index (BMI) is also a well-known factor that triggers the early pubarche, thelarche, and menarche in children (Rosenfield et al., 2009).

The timing of menarche impacts the reproductive period and estrogen exposure throughout a woman's lifetime. Both earlier and later pubertal development, compared to those maturing normally, are associated with a higher risk of various adverse health outcomes, such as cancers, cardiovascular diseases, digestive system disorders, metabolic diseases, and detrimental neurocognitive effects (Day et al., 2015; Mishra et al., 2021).

The effects of heavy metal exposure on the sexual maturation have been demonstrated in several experimental studies. For instance, prenatal exposure to Cd or Pb led to late vaginal opening in female rats due to the suppression of growth hormone and sexual hormones related to maturation (Ishitobi &Watanabe, 2005; Dearth et al., 2002). In addition, Hg exposure was reported to alter sex steroids in both male and female rats (Tan et al., 2009).

The relationship between heavy metal exposure and age at menarche has been investigated across various human populations. However, most studies have been constrained by small sample sizes and confined to Western countries. In a prospective cohort study involving teenage girls in the United States (n = 211, studied 2005–2008), those with elevated urinary Cd levels exhibited delayed pubertal development and onset of menarche (Reynolds et al., 2020). In a mother and child cohort in Mexico (n = 200 pairs, studied 1997–2004), maternal second-trimester blood Pb levels demonstrated a significant association with the child's later onset of menarche (Jansen et al., 2018). Similarly, maternal bone Pb levels and their children's blood Pb levels were significantly associated with delayed menarche within the same Mexican cohort (Liu et al., 2019). However, some studies have reported conflicting findings. Total Hg levels in hair were associated with earlier menarche in a Flemish population (n = 210, Croes et al., 2014). Studies on the Korean population are limited, and the observations are also inconsistent. A study employing the sixth Korean National Health and Nutrition Examination Survey (6th KNHANES) database reported the associations of blood Pb and Hg levels with earlier menarche in female children and adolescents aged 10–18 (n = 179, Choi, 2020). In contrast, another study reported the opposite direction of association, i.e., delayed menarche with higher urinary Cd and Hg levels in girls aged 9–11 years (n = 233) who participated in the third Korean National Environmental Health Survey (3rd KoNEHS) database (Lee et al., 2021).

This study aimed to understand the association between blood Cd, Pb, and Hg levels and the age at menarche using a nationally representative Korean population with a reasonable sample size. In contrast to the previous Korean studies that were restricted to teenager girls (Choi, 2020; Lee et al., 2021), we constructed a group of women encompassing not only teenagers but also adults and elders, from multiple cycles of KNHANES 2008–2017 (4th-7th KNHANES), and evaluated the association of blood heavy metals on the timing of menarche. The findings of this study will help identify heavy metal risk factors that may influence timing of pubertal onset of women at the current levels of exposure.