MON-159 - Associations of Oxidative Stress and Antioxidant Capacity with Longitudinal Hormone Concentrations in Mid-Life Women

Background: While declining estradiol in midlife women has been linked to elevated oxidative stress, oxidative stress may also contribute to ovarian aging and subsequent declines in sex-steroid hormones. However, few studies have considered the roles of oxidative stress or antioxidant capacity in sex-steroid hormone concentrations of midlife women.

Objectives: We examined whether higher oxidative stress and lower antioxidant capacity were associated with longitudinal sex-steroid hormone concentrations in midlife women and considered differences in associations by baseline menopausal status.

Methods: In 721 pre- and perimenopausal women (45-54 y) from the Baltimore, MD area, we assessed serum 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of free-radical induced oxidative lesions in mitochondrial DNA, and total antioxidant capacity (TAC), a biomarker reflecting the ability to eliminate reactive oxygen species, in year 1 of the study. Serum estradiol, testosterone, and progesterone were measured and averaged across four weekly samples (to approximate one menstrual cycle) in study years 1 - 4. We examined associations of 8-OHdG and TAC with hormone concentrations using multivariable linear mixed models with a random intercept, and included a product term to assess differences in associations by baseline menopausal status (defined based on days since last menstrual period and number of periods in the past year; premenopausal: < 60 days and >10 periods; perimenopausal: >=60 days or >=10 periods).

Results: Women in the study were primarily non-Hispanic White (66%) or Black (30%), college-educated (64%), and premenopausal (60%). An IQR increase in 8-OHdG was associated with 15.1% (95% CI: -19.4, -10.6) lower estradiol, 13.6% (95% CI: -17.9, -9.1) lower testosterone, and 16.3% (95% CI: -23.4, -8.7) lower progesterone. These associations were strongest in women who were in perimenopause at baseline, in whom an IQR increase in 8-OHdG was associated with lower estradiol (-18.1; 95% CI: -24.6, -11.1), testosterone (-18.4; 95% CI: -25.1, -11.1), and progesterone (-20.4%; 95% CI: -29.9, -9.6). An IQR decrease in TAC was associated with 10.5% (95% CI: -15.4, -5.4) lower estradiol and 9.1% (95% CI: -13.9, -4.0) lower testosterone. These associations were primarily driven by women who were in perimenopause at baseline, in whom an IQR decrease in TAC was associated with lower estradiol (-13.1%; 95% CI: -19.7, -6.0) and testosterone (-12.0%; 95% CI: -18.9, -4.6).

Conclusions: In midlife women, higher 8-OHdG and lower TAC were prospectively associated with lower sex-steroid hormones, particularly in perimenopause. Future research may consider oxidative stress as a possible mechanism by which lifestyle and environmental exposures impact hormones trajectories in midlife women.

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