Cumulative phthalate exposure and risk of hot flashes within the Midlife Women’s Health Study

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BACKGROUND AND AIM: Hot flashes are intermittent and disruptive sensations of heat in the upper body and can have a significant impact on quality of life in perimenopausal women. Low estrogen levels are associated with an increased risk of hot flashes. Phthalates are endocrine disrupting chemicals of widespread exposure, with some metabolites having estrogenic properties; however, few studies have evaluated the association between phthalate concentrations and hot flash occurrence, especially across multiple years in perimenopausal women. METHODS: The Baltimore Midlife Women’s Health Study recruited women aged 45 and 54 years (2007 – 2015), collecting data on self-report of hot flash outcomes and biospecimens for laboratory analyses, including urinary phthalate metabolite concentrations. We employed generalized linear mixed models (GLMMs), with phthalate measures operationalized as cumulatively averaged geometric means updated for each year, to conduct mixed effects logistic regression and calculate odds ratios (ORs) for risk of ever-experiencing hot flashes and hot flash severity (dichotomized as none or mild vs moderate or severe), adjusting for participant characteristics as potential confounders. RESULTS:A total of 758 participants provided up to 4 years of follow-up data. At baseline, 343 (45.8%) women reported ever experiencing a hot flash and 225 (30.1%) reported experiencing moderate or severe hot flashes. In adjusted models, only the sum of personal care product phthalate metabolites (∑PCP, the sum of monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), and mono-isobutyl phthalate (MiBP)) updated over the 4-year study period was associated with moderate and severe hot flashes (OR: 1.18; 95%CI: 1.01 – 1.38). No other individual phthalate metabolite or summary measure was associated with ever experiencing hot flashes or hot flash severity. CONCLUSIONS:Higher concentrations of phthalates from PCPs were associated with experiencing moderate or severe hot flashes across the perimenopausal period. Reducing exposure to phthalates from PCPs may help to reduce risk of moderate/severe hot flashes in middle-aged women. KEYWORDS: phthalates, endocrine disrupting chemicals, reproductive outcomes