Endothelial Function, But Not Carotid Intima-Media Thickness, Is Affected Early in Menopause and Is Associated with Severity of Hot Flushes

Context: The effect of early menopause on indices of vascular function has been little studied. Objective: The objective of the study was to investigate the effect of early menopause on indices of subclinical atherosclerosis and identify predictors of those indices in early menopausal women. Design, Setting, and Participants: This was a cross-sectional study that included 120 early menopausal women (age range 42-55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women. Main Outcome Measures: Brachial artery flow-mediated dilation (FMD) and common carotid intima-media thickness (IMT) were studied. Estrogen receptor (ER)-alpha (rs2234693 T-->C and rs9340799 A-->G) and ER beta (rs4986938 A-->G) polymorphisms were studied in menopausal women. Results: FMD was significantly lower in early menopausal women compared with controls (5.43 +/- 2.53 vs. 8.74 +/- 3.17%, P < 0.001), whereas IMT did not differ between groups (P > 0.8). Severity of hot flushes was the most important independent predictor for FMD (P < 0.001) in menopausal women. Women with moderate/severe/very severe hot flushes had impaired FMD in contrast to women with no/mild hot flushes or controls. Women with no/mild hot flushes did not differ compared with controls. Age and systolic blood pressure were the main determinants of IMT (both P = 0.004). ER polymorphisms were not associated with vascular parameters. Conclusions: Impairment of endothelial function is present in the early menopausal years, whereas carotid IMT is not affected. Severity of hot flushes is the main determinant of endothelial dysfunction in early menopausal women. The studied ER polymorphisms do not offer important information on vascular health in early menopause. (J Clin Endocrinol Metab 95: 1199-1206, 2010)