Greater exposure to heavy metals linked with earlier age of natural menopause for US women
Women who have been exposed to higher levels of certain heavy metals tend to reach natural menopause earlier, according to a new study published in Environmental Advances.
Experiencing natural menopause at an earlier age is linked with greater risk of heart disease, osteoporosis, cognitive decline, and death from any cause. While genetics can influence age at menopause, environmental factors are increasingly recognized as modifiable contributors. With research on exposure to heavy metal mixtures and reproductive aging in women remaining limited, this new study adds to growing evidence that environmental exposures may be underdiscussed as drivers of reproductive aging.
Analyzing survey data and biological samples of 1,573 postmenopausal women across the US, researchers Xin Fang, Shruthi Mahalingaiah, and Joel Schwartz examined five heavy metals – lead, cadmium, arsenic, mercury, and thallium – due to known or suspected hormone-disrupting properties. They included data from eight consecutive cycles of the National Health and Nutrition Examination Survey (NHANES), collected between 2003 and 2018. Levels of the metals studied were measured from participant blood and urine samples.
They then used multiple advanced statistical methods, including two mixture modeling approaches and a machine-learning model, to assess how the combination of all five metals together related to the age at which women reached menopause. They next jointly ranked the metals against lifestyle and sociodemographic factors. They found that all five metals out-ranked even smoking, which is well known to accelerate reproductive aging, and that lead, thallium, and cadmium in particular were most strongly correlated with faster reproductive aging.
One methodological challenge the team addressed was that blood lead levels naturally change after menopause; as bone breaks down over time, accumulated lead re-enters the bloodstream. This can make lead look artificially low before menopause and higher afterward. The team estimated what each woman’s blood lead level would have been before menopause using one of their advanced statistical techniques to get a more accurate picture of her actual prior exposure.
Specifically, women with higher combined exposure to the metal mixture reached menopause approximately 10 months earlier per quintile increase in exposure, on average. Corrected blood lead was the single strongest contributor to this association, and notably ranked as more important than income, body weight, number of pregnancies, smoking, education level, and race/ethnicity.
Thallium ranked second among the metals, which the team explained could pose significant issue for population health due to its current under-regulation. The metal should undergo evaluation for inclusion on the EPA Contaminant Candidate List and greater regulatory attention, they suggest.
The researchers additionally note that because this was a cross-sectional study, meaning it captured a snapshot in time rather than following participants over years, the results show associations, not definitive proof of cause and effect. Longer-term studies are necessary to advance this science further, they explain.
