Endogenous sex hormones impact the progression of subclinical atherosclerosis in women during the menopausal transition.

OBJECTIVE: To determine whether endogenous sex hormones (estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and follicle stimulating hormone (FSH)) are longitudinally associated with progression of atherosclerosis among women at midlife.

METHODS: 249 Pre- or early peri-menopausal women (42-57 years) from the Study of Women's Health Across the Nation (SWAN) were followed for up to 9 years (median = 3.7 years) and had up to 5 repeated measures of common carotid intima-media thickness (IMT) and adventitial diameter (AD). Linear mixed models were used for statistical analysis. Final models included age at baseline, time since baseline, cycle day of blood draw, race, income, SBP, BMI, insulin resistance index, lipids, C-reactive protein and co-morbidity.

RESULTS: In final models for IMT, each one log unit decrease in SHBG was associated with a 0.005 mm/year increase in IMT progression (P = 0.003). E2, T, and FSH were not associated with level or progression of IMT. For AD, each one log unit decrease in E2 was associated with a 0.012 mm/year increase in AD progression (P = 0.04) and each one log unit increase in FSH was associated with a 0.016 mm/year increase in AD progression (P = 0.003). T and SHBG were not associated with progression or level of AD.

CONCLUSIONS: Independent of SBP, BMI, lipids and other covariates, lower E2 and SHBG, and higher FSH were associated with increased subclinical atherosclerosis progression in women at midlife.