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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Main Authors: Maria E. Cinzori, Diana C. Pacyga, Elnur Babayev, Francesca E. Duncan, Zhong Li, Paige L. Williams, Jodi A. Flaws, Rita S. Strakovsky
Format: Article
Language:English
Published: Elsevier 2023-02-01
Series:Environment International
Subjects:
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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