Urinary phthalate metabolite concentrations and serum hormone levels in pre- and perimenopausal women from the Midlife Women's Health Study

Background: Phthalate exposure is associated with altered reproductive function, but little is known about associations between phthalate and hormone levels in midlife women. Methods: This cross-sectional analysis includes 45-54-year-old pre- and perimenopausal women from Baltimore, MD and its surrounding counties enrolled in the Midlife Women's Health Study (n = 718). Serum and urine samples were collected from participants once a week for four consecutive weeks to span the menstrual cycle. Serum samples were assayed for estradiol, testosterone, progesterone, sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH), and geometric means were calculated for each hormone across all four weeks. Urine samples were analyzed for nine phthalate metabolites from pools of one-to-four urine samples. Phthalate metabolite concentrations were specific gravity-adjusted and assessed as individual metabolites or as molar sums of metabolites from common parents (di(2-ethylhexyl) phthalate metabolites, FDEHP), exposure sources (plastic, FPlastics; personal care products, FPCP), biological activity (anti-androgenic, FAA), and sum of all metabolites (FPhthalates). We used linear regression models to assess overall associations of phthalate metabolites with hormones, controlling for important demographic, lifestyle, and health factors. We also explored whether associations differed by menopause status, body mass index (BMI), and race/ethnicity. Results: Most participants were non-Hispanic white (67%) or black (29%), college-educated (65%), employed (80%), and had somewhat higher mean urinary phthalate metabolite concentrations than other U.S. women. Overall, the following positive associations were observed between phthalate metabolites and hormones: FDEHP (%Delta: 4.9; 95%CI: 0.5, 9.6), FPlastics (%Delta: 5.1; 95%CI: 0.3, 10.0), and FAA (%Delta: 7.8; 95%CI: 2.3, 13.6) with estradiol; MiBP (%Delta: 6.6; 95%CI: 1.5, 12.1) with testosterone; FDEHP (%Delta: 8.3; 95%CI: 1.5, 15.6), FPlastics (%Delta: 9.8; 95%CI: 2.4, 17.7), MEP (%Delta: 4.6; 95%CI: 0.1, 9.2), FPCP (%Delta: 6.0; 95%CI: 0.2, 12.2), FPhthalates (%Delta: 9.0; 95%CI: 2.1, 16.5), and FAA (%Delta: 12.9; 95%CI: 4.4, 22.1) with progesterone; and MBP (%Delta: 8.5; 95%CI: 1.2, 16.3) and FAA (%Delta: 9.0; 95%CI: 1.3, 17.4) with AMH. Associations of phthalate metabolites with hormones differed by menopause status (strongest in premenopausal women for estradiol, progesterone, and FSH), BMI (strongest in obese women for progesterone), and race/ethnicity (strongest in nonHispanic white women for estradiol and AMH).