Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women
Background/objectives: Women are ubiquitously exposed to endocrine disruptors, including phthalates. Ovarian follicles undergoing folliculogenesis (indirectly measured by ovarian volume) produce anti-Müllerian hormone (AMH) and estradiol (E2). We evaluated associations of phthalates with ovarian vol...
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Elsevier
2023-02-01
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Series: | Environment International |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412023000442 |
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author | Maria E. Cinzori Diana C. Pacyga Elnur Babayev Francesca E. Duncan Zhong Li Paige L. Williams Jodi A. Flaws Rita S. Strakovsky |
author_facet | Maria E. Cinzori Diana C. Pacyga Elnur Babayev Francesca E. Duncan Zhong Li Paige L. Williams Jodi A. Flaws Rita S. Strakovsky |
author_sort | Maria E. Cinzori |
collection | DOAJ |
description | Background/objectives: Women are ubiquitously exposed to endocrine disruptors, including phthalates. Ovarian follicles undergoing folliculogenesis (indirectly measured by ovarian volume) produce anti-Müllerian hormone (AMH) and estradiol (E2). We evaluated associations of phthalates with ovarian volume to assess whether this explained prior positive associations of phthalates with AMH and E2. Methods: Women ages 45–54 years (n = 614) had transvaginal ultrasounds of right/left ovaries to calculate mean ovarian volume. Women provided up-to-four urine and blood samples for quantifying AMH (first serum sample), E2 (all serum samples), and nine phthalate metabolites (from pooled urine, representing six parent phthalates). Multivariable linear or logistic regression models (for individual phthalate biomarkers), as well as weighted quantile sum (WQS) regression (for mixture analyses) evaluated associations of phthalate biomarkers with ovarian volume. Using cross-sectional mediation analysis, we assessed whether associations of phthalates with ovarian volume partially explained those of phthalates with AMH or E2. Results: Most women were non-Hispanic White (68%) and pre-menopausal (67%) with higher urinary phthalate metabolite concentrations than U.S. women. In single-pollutant models, 10% increases in mono(3-carboxypropyl) phthalate (MCPP) and monobenzyl phthalate (MBzP) were associated with 0.44% (95% CI: −0.02%, 0.91%) and 0.62% (95% CI: 0.02%, 1.23%) larger ovarian volumes, respectively. As a cumulative mixture, 10% increases in the phthalate mixture were associated with 2.89% larger ovarian volume (95%CI: 0.27, 5.59) with MCPP (35%) and MBzP (41%) identified as major contributors. Higher ovarian volume due to a 10% increase in MBzP (indirect effect OR: 1.004; 95% CI: 1.00, 1.01) explained 16% of the positive association between MBzP and higher AMH, whereas higher ovarian volume due to a 10% increase in MCPP (indirect effect %Δ: 0.11; 95% CI: −0.01, 0.22) explained 23% of the positive association between MCPP and E2. Conclusion: In this cross-sectional study, phthalates were associated with increased ovarian volume, with implications for midlife hormone production. |
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spelling | doaj.art-a175657c87f94217a45f32d07ab913c62023-02-18T04:16:18ZengElsevierEnvironment International0160-41202023-02-01172107771Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife womenMaria E. Cinzori0Diana C. Pacyga1Elnur Babayev2Francesca E. Duncan3Zhong Li4Paige L. Williams5Jodi A. Flaws6Rita S. Strakovsky7Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, United States; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, United States; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, United States; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, United StatesDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United StatesDepartment of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United StatesRoy J. Carver Biotechnology Center, University of Illinois, Urbana-Champaign, IL 61801, United StatesDepartment 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 StatesDepartment of Comparative Biosciences, University of Illinois, Urbana-Champaign, IL 61802, United StatesDepartment of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, United States; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, United States; Corresponding author at: 236C Trout Building, 469 Wilson Road, United States.Background/objectives: Women are ubiquitously exposed to endocrine disruptors, including phthalates. Ovarian follicles undergoing folliculogenesis (indirectly measured by ovarian volume) produce anti-Müllerian hormone (AMH) and estradiol (E2). We evaluated associations of phthalates with ovarian volume to assess whether this explained prior positive associations of phthalates with AMH and E2. Methods: Women ages 45–54 years (n = 614) had transvaginal ultrasounds of right/left ovaries to calculate mean ovarian volume. Women provided up-to-four urine and blood samples for quantifying AMH (first serum sample), E2 (all serum samples), and nine phthalate metabolites (from pooled urine, representing six parent phthalates). Multivariable linear or logistic regression models (for individual phthalate biomarkers), as well as weighted quantile sum (WQS) regression (for mixture analyses) evaluated associations of phthalate biomarkers with ovarian volume. Using cross-sectional mediation analysis, we assessed whether associations of phthalates with ovarian volume partially explained those of phthalates with AMH or E2. Results: Most women were non-Hispanic White (68%) and pre-menopausal (67%) with higher urinary phthalate metabolite concentrations than U.S. women. In single-pollutant models, 10% increases in mono(3-carboxypropyl) phthalate (MCPP) and monobenzyl phthalate (MBzP) were associated with 0.44% (95% CI: −0.02%, 0.91%) and 0.62% (95% CI: 0.02%, 1.23%) larger ovarian volumes, respectively. As a cumulative mixture, 10% increases in the phthalate mixture were associated with 2.89% larger ovarian volume (95%CI: 0.27, 5.59) with MCPP (35%) and MBzP (41%) identified as major contributors. Higher ovarian volume due to a 10% increase in MBzP (indirect effect OR: 1.004; 95% CI: 1.00, 1.01) explained 16% of the positive association between MBzP and higher AMH, whereas higher ovarian volume due to a 10% increase in MCPP (indirect effect %Δ: 0.11; 95% CI: −0.01, 0.22) explained 23% of the positive association between MCPP and E2. Conclusion: In this cross-sectional study, phthalates were associated with increased ovarian volume, with implications for midlife hormone production.http://www.sciencedirect.com/science/article/pii/S0160412023000442PhthalatesAnti-Müllerian hormoneEstradiolOvarian volumeMidlife |
spellingShingle | Maria E. Cinzori Diana C. Pacyga Elnur Babayev Francesca E. Duncan Zhong Li Paige L. Williams Jodi A. Flaws Rita S. Strakovsky Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women Environment International Phthalates Anti-Müllerian hormone Estradiol Ovarian volume Midlife |
title | Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women |
title_full | Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women |
title_fullStr | Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women |
title_full_unstemmed | Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women |
title_short | Ovarian volume partially explains associations of phthalate biomarkers with anti-Müllerian hormone and estradiol in midlife women |
title_sort | ovarian volume partially explains associations of phthalate biomarkers with anti mullerian hormone and estradiol in midlife women |
topic | Phthalates Anti-Müllerian hormone Estradiol Ovarian volume Midlife |
url | http://www.sciencedirect.com/science/article/pii/S0160412023000442 |
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