Reproductive toxicology (Elmsford, N.Y.) · 2026
Urinary phthalate metabolite concentrations and oxidative stress biomarkers in pre- and perimenopausal women from the Midlife Women's Health Study.
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Inman Zane Cutright, Cinzori Maria E, Guetterman Heather M, Seaton Taylor, Strakovsky Rita S, Flaws Jodi A
Аннотация
BACKGROUND: Women are ubiquitously exposed to phthalates. Phthalates are linked to early reproductive aging and more frequent hot flashes in midlife women, but little is known about the mechanisms underlying phthalate-induced reproductive aging. We assessed associations of phthalate exposure with oxidative stress in midlife women, and whether oxidative stress mediates phthalate-induced hot flashes.
METHODS: Women ages 45-54 years (n = 687) provided up to four urine samples for quantifying nine urinary phthalate metabolites and serum samples for quantifying 8-hydroxy-2'-deoxyguanosine (8-OHdG) and total antioxidant capacity (TAC). We used multivariable linear regression models to evaluate associations of specific gravity-adjusted phthalates with 8-OHdG and TAC, and whether associations differed by alcohol use and smoking status. We examined the extent to which 8-OHdG and TAC explained associations between phthalates and hot flashes using a causal mediation framework.
RESULTS: Each doubling of ΣDEHP was associated with 2.9% higher 8-OHdG (95% confidence interval (CI): 0.0, 5.9). In addition, doublings of ΣDEHP and MBzP were associated with -77.4 μM (95%CI: -105.2, -49.6) and -29.7 μM (95%CI: -55.9, -3.5) lower TAC, respectively. However, some metabolites (MCPP, MiBP) were associated with lower 8-OHdG and/or higher TAC. Some of these associations varied by alcohol use and smoking status. 8-OHdG and TAC did not mediate previously observed associations of phthalates with hot flash prevalence, frequency, or severity.
CONCLUSIONS: Phthalate exposure may modulate oxidative stress pathways in midlife women, but additional studies are needed to understand long-term implications for reproductive aging.
METHODS: Women ages 45-54 years (n = 687) provided up to four urine samples for quantifying nine urinary phthalate metabolites and serum samples for quantifying 8-hydroxy-2'-deoxyguanosine (8-OHdG) and total antioxidant capacity (TAC). We used multivariable linear regression models to evaluate associations of specific gravity-adjusted phthalates with 8-OHdG and TAC, and whether associations differed by alcohol use and smoking status. We examined the extent to which 8-OHdG and TAC explained associations between phthalates and hot flashes using a causal mediation framework.
RESULTS: Each doubling of ΣDEHP was associated with 2.9% higher 8-OHdG (95% confidence interval (CI): 0.0, 5.9). In addition, doublings of ΣDEHP and MBzP were associated with -77.4 μM (95%CI: -105.2, -49.6) and -29.7 μM (95%CI: -55.9, -3.5) lower TAC, respectively. However, some metabolites (MCPP, MiBP) were associated with lower 8-OHdG and/or higher TAC. Some of these associations varied by alcohol use and smoking status. 8-OHdG and TAC did not mediate previously observed associations of phthalates with hot flash prevalence, frequency, or severity.
CONCLUSIONS: Phthalate exposure may modulate oxidative stress pathways in midlife women, but additional studies are needed to understand long-term implications for reproductive aging.