Metabolism-disrupting compounds and metabolic health during the menopausal transition: a narrative review

Substantial evidence has linked endocrine-disrupting chemicals and other compounds to increased risk of elevated adiposity and adverse metabolic outcomes. Individuals may be particularly susceptible to these metabolism-disrupting chemicals or compounds (MDC) during sensitive periods. The menopausal transition is a sensitive window marked by increased risk of obesity, metabolic syndrome, and cardiovascular disease that continues into the postmenopausal period; however, evidence on modifiable risk factors, such as MDC exposure, in perimenopausal individuals is limited. Therefore, we conducted a review to understand the breadth of literature evaluating relationships of MDC exposure with metabolic health outcomes (e.g. body weight/composition, glycemic control, lipid profiles, blood pressure) across the menopausal transition. We identified 28 studies using data from four U.S.-based cohorts of midlife women. Overall, studies suggest that phthalates and other nonpersistent chemicals (7 studies), per- and polyfluoroalkyl substances (7 studies), persistent organic pollutants (3 studies), heavy metals (5 studies), and air pollutants (6 studies) were associated with increases in body fat, unfavorable adipokine profiles, adverse lipid profiles, and/or higher risk of type 2 diabetes and hypertension. Several studies identified differences by race/ethnicity. Although few studies stratified by menopause status, some results suggest that perimenopause may be a sensitive window of exposure to MDCs. Additional data are needed to identify susceptible windows of exposure during midlife, particularly in more diverse populations. Future research should consider examining cumulative exposure to multi-pollutant mixtures and identifying susceptible populations and mitigation strategies during this period.