Urinary phthalate metabolite concentrations and oxidative stress biomarkers in pre- and perimenopausal women from the Midlife Women's Health Study.

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.