The Chemical Exposome on Ovarian Aging in Adult Women: a Narrative Review

The effects of environmental exposures on female reproductive outcomes in early life are well studied. In contrast, we do not understand the broad range of chemical risk factors on women's reproductive physiology during midlife. The purpose of this review is to summarize the epidemiological literature on associations between environmental exposures (i.e., phthalates, phenols, per- and polyfluoroalkyl substances (PFAS), toxic metals, air pollution, and persistent organic compounds) and ovarian function and sex hormones as women approach and transverse the menopausal transition.

There is accumulating evidence of associations between phthalate metabolites, air pollution, and chlorinated organic chemical exposures and decreased ovarian function and associations between selected PFAS chemicals and increased testosterone or decreased estradiol, suggesting that these chemicals are risk factors. More studies are needed to confirm emerging evidence regarding other chemicals and reproductive aging markers.

Most studies were cross-sectional in design or restricted to couples receiving infertility treatment, which may induce selection bias and reduce generalizability. Additionally, there has been limited research in ethnically, racially, or socioeconomically diverse populations. Nevertheless, PFAS, phthalate metabolites, air pollution, and chlorinated organic solvents are potential risk factors for adverse reproductive outcomes in adult women. An exposome approach using advanced omics technologies to capture a broad chemical range of repeated measures can address knowledge gaps needed to identify risk factors.