Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause
Open Access
- 3 February 2023
- journal article
- research article
- Published by The Endocrine Society in Journal of the Endocrine Society
- Vol. 7 (4), bvad024
- https://doi.org/10.1210/jendso/bvad024
Abstract
Phthalates, ubiquitous endocrine-disrupting chemicals, may impact ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1,189 multi-racial/ethnic women aged 45-56 years without hormone therapy from the Study of Women’s Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999-2000 and 2002-2003, resulting in a total of 2,111 observations. Linear mixed-effect models were used to calculate percent differences (%D) and 95% confidence intervals (95% CIs) in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%, 95% CI: -3.66, -0.47), and MnBP with testosterone (%D: -1.99%, 95% CI: -3.82, -0.13), after adjusting for multiple comparisons with false discovery rates<5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%, 95% CI: -24.10, -3.14), MEHHP (%D: -15.58%, 95% CI: -24.59, -5.50), and MEOHP (%D: -13.50%, 95% CI: -22.93, -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates.Keywords
Funding Information
- National Institutes of Health
- National Institute on Aging
- National Institute of Nursing Research
- NIH Office of Research on Women’s Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, U19AG063720)
- SWAN Repository (U01AG017719)
- National Center for Research Resources and the National Center for Advancing Translational Sciences (UL1 RR024131))
- National Institute of Environmental Health Sciences (R01-ES026578, 01-ES026964, P30-ES017885))
- Centers for Disease Control and Prevention
- National Institute for Occupational Safety and Health (T42-OH008455))
This publication has 52 references indexed in Scilit:
- The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence: a pilot studyReproduction, 2014
- A characterization of the relationship of ovarian reserve markers with ageFertility and Sterility, 2012
- Investigation of Relationships between Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols and Pubertal Stages in GirlsEnvironmental Health Perspectives, 2010
- Phthalates and other additives in plastics: human exposure and associated health outcomesPhilosophical Transactions B, 2009
- A Mixture of Five Phthalate Esters Inhibits Fetal Testicular Testosterone Production in the Sprague-Dawley Rat in a Cumulative, Dose-Additive MannerToxicological Sciences, 2008
- Peroxisome Proliferator-Activated Receptors as Mediators of Phthalate-Induced Effects in the Male and Female Reproductive Tract: Epidemiological and Experimental EvidencePPAR Research, 2007
- Quantification of 22 phthalate metabolites in human urineJournal of Chromatography B, 2007
- Longitudinal Analysis of the Association Between Vasomotor Symptoms and Race/Ethnicity Across the Menopausal Transition: Study of Women’s Health Across the NationAmerican Journal of Public Health, 2006
- Evaluation of anti-androgenic activity of di-(2-ethylhexyl)phthalateToxicology, 2005
- Physical Activity Patterns in a Diverse Population of WomenPreventive Medicine, 1999