Association of phthalate exposure and endogenous hormones with self-reported sleep disruptions: results from the Midlife Women's Health Study

Abstract Objective: Follicle-stimulating hormone and estradiol (E 2 ) have been associated with sleep in midlife women, however, few studies have examined the association of other hormones or environmental chemical exposure such as phthalates, with self-reported sleep quality. We assessed the relationship of self-reported sleep with hormones and phthalates. Methods: In total, 762 women (aged 45-54 y, 459 premenopausal, and 303 perimenopausal) from the Midlife Women's Health Study answered self-reported questions regarding the frequency of sleep disturbances, insomnia, and restless sleep. Serum E 2 , progesterone, testosterone, serum hormone binding globulin, free E 2 index, free testosterone index, E 2 :progesterone, and E 2 :testosterone were measured. Summary measures of phthalate mixtures, including the phthalates from plastic sources (sumPLASTIC), personal care products (sumPCP), di-(2-ethyhexyl) phthalate (sumDEHP), anti-androgenic phthalates (sumAA), and all phthalate metabolites measured (sumALL), were calculated from urinary phthalate metabolites. Ordinal logistic regression was used to fit each outcome sleep measure with all hormones and summary phthalates. Results: Progesterone and testosterone were significantly negatively associated with the frequency of sleep disturbances and insomnia. Free testosterone index was also negatively associated with insomnia frequency. E 2 :progesterone was positively associated with frequency of sleep disturbances and restless sleep in self-reported nonsmokers. SumPCP and sumALL were significantly negatively associated with frequency of sleep disturbances, insomnia, and restless sleep. SumDEHP and sumPLASTIC were negatively associated with insomnia frequency. Further, the direction of association between phthalates and sleep appears to be dependent on the quartile of phthalate exposure. All significant associations between phthalates and sleep were in self-reported nonsmokers or former smokers. Conclusions: Our study supports previous literature that hormones beyond follicle-stimulating hormone and E 2 are associated with sleep disruptions in menopause. Further, we are among the first to show that phthalate exposure is associated with sleep disruptions in midlife women.