Endothelial Function Is Impaired across the Stages of the Menopause Transition in Healthy Women

CONTEXT: The stages of the menopause transition are characterized by changes in ovarian hormones and increased cardiovascular disease (CVD) risk factors and vasomotor symptoms that may adversely affect vascular health. OBJECTIVE: We tested the hypothesis that endothelial function, a predictor of CVD, would be reduced across the stages of the menopause transition, independent of CVD risk factors and vasomotor symptoms. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 132 healthy women from the general community aged 22-70 yr, categorized as premenopausal (n = 33, 32 ± 6 yr; mean ± SD), early perimenopausal (n = 20, 49 ± 3 yr) or late perimenopausal (n = 22, 50 ± 4 yr), or early (n = 30, 55 ± 3 yr) or late postmenopausal (n = 27, 61 ± 4 yr). MAIN OUTCOME: Endothelial-dependent vasodilation was measured by brachial artery flow-mediated dilation (FMD) using ultrasound. RESULTS: Brachial artery FMD was significantly different among the groups (P < 0.001). It was highest in premenopausal women (9.9 ± 2.1%) with progressive decrements in perimenopausal (early: 8.2 ± 2.5%; late: 6.5 ± 1.9%) and postmenopausal women (early: 5.5 ± 1.9%; late: 4.7 ± 1.7%). Adjustment for risk factors, vasomotor symptoms, and sex hormones did not alter the association (P < 0.001). In subgroup analyses of women aged 50-59 yr, brachial artery FMD was lower in late peri- and early and late postmenopausal compared with early perimenopausal women (P < 0.001) but was not different between late perimenopausal and either early or late postmenopausal women. CONCLUSIONS: Our findings suggest that a decline in endothelial function begins during the early stages of menopause (perimenopause) and worsens with the loss of ovarian function and prolonged estrogen deficiency. These data add to the accumulating evidence that the perimenopausal window is a critical time period for adverse changes in CVD risk.