Catheryne Chiang1, Diana C Pacyga2, Rita S Strakovsky3, Rebecca L Smith4, Tamarra James-Todd5, Paige L Williams6, Russ Hauser5, Daryl D Meling1, Zhong Li7, Jodi A Flaws8. 1. Department of Comparative Biosciences, University of Illinois, Urbana, IL 61802, United States. 2. Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48823, United States; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48823, United States; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48823, United States. 3. Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48823, United States; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48823, United States. 4. Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, United States; Department of Pathobiology, University of Illinois, Urbana, IL 61802, United States. 5. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. 6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States. 7. Roy J. Carver Biotechnology Center, University of Illinois, Urbana, IL 61801, United States. 8. Department of Comparative Biosciences, University of Illinois, Urbana, IL 61802, United States; Institute for Genomic Biology, University of Illinois, Urbana, IL 61801, United States. Electronic address: jflaws@illinois.edu.
Abstract
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-Müllerian 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, ∑DEHP), exposure sources (plastic, ∑Plastics; personal care products, ∑PCP), biological activity (anti-androgenic, ∑AA), and sum of all metabolites (∑Phthalates). 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: ∑DEHP (%Δ: 4.9; 95%CI: 0.5, 9.6), ∑Plastics (%Δ: 5.1; 95%CI: 0.3, 10.0), and ∑AA (%Δ: 7.8; 95%CI: 2.3, 13.6) with estradiol; MiBP (%Δ: 6.6; 95%CI: 1.5, 12.1) with testosterone; ∑DEHP (%Δ: 8.3; 95%CI: 1.5, 15.6), ∑Plastics (%Δ: 9.8; 95%CI: 2.4, 17.7), MEP (%Δ: 4.6; 95%CI: 0.1, 9.2), ∑PCP (%Δ: 6.0; 95%CI: 0.2, 12.2), ∑Phthalates (%Δ: 9.0; 95%CI: 2.1, 16.5), and ∑AA (%Δ: 12.9; 95%CI: 4.4, 22.1) with progesterone; and MBP (%Δ: 8.5; 95%CI: 1.2, 16.3) and ∑AA (%Δ: 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 non-Hispanic white women for estradiol and AMH). CONCLUSIONS: We found that phthalate metabolites were positively associated with several hormones in midlife women, and that some demographic and lifestyle characteristics modified these associations. Future longitudinal studies are needed to corroborate these findings in more diverse midlife populations.
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-Müllerian 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, ∑DEHP), exposure sources (plastic, ∑Plastics; personal care products, ∑PCP), biological activity (anti-androgenic, ∑AA), and sum of all metabolites (∑Phthalates). 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: ∑DEHP (%Δ: 4.9; 95%CI: 0.5, 9.6), ∑Plastics (%Δ: 5.1; 95%CI: 0.3, 10.0), and ∑AA (%Δ: 7.8; 95%CI: 2.3, 13.6) with estradiol; MiBP (%Δ: 6.6; 95%CI: 1.5, 12.1) with testosterone; ∑DEHP (%Δ: 8.3; 95%CI: 1.5, 15.6), ∑Plastics (%Δ: 9.8; 95%CI: 2.4, 17.7), MEP (%Δ: 4.6; 95%CI: 0.1, 9.2), ∑PCP (%Δ: 6.0; 95%CI: 0.2, 12.2), ∑Phthalates (%Δ: 9.0; 95%CI: 2.1, 16.5), and ∑AA (%Δ: 12.9; 95%CI: 4.4, 22.1) with progesterone; and MBP (%Δ: 8.5; 95%CI: 1.2, 16.3) and ∑AA (%Δ: 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 obesewomen for progesterone), and race/ethnicity (strongest in non-Hispanic white women for estradiol and AMH). CONCLUSIONS: We found that phthalate metabolites were positively associated with several hormones in midlife women, and that some demographic and lifestyle characteristics modified these associations. Future longitudinal studies are needed to corroborate these findings in more diverse midlife populations.
Authors: Karen K Chiu; Shah Tauseef Bashir; Ahmed M Abdel-Hamid; Lindsay V Clark; Mary J Laws; Isaac Cann; Romana A Nowak; Jodi A Flaws Journal: Toxics Date: 2022-02-06
Authors: Diana C Pacyga; Brad A Ryva; Romana A Nowak; Serdar E Bulun; Ping Yin; Zhong Li; Jodi A Flaws; Rita S Strakovsky Journal: Int J Environ Res Public Health Date: 2022-02-26 Impact factor: 3.390