Endothelial function in women of the Kronos Early Estrogen Prevention Study

OBJECTIVE Endothelial dysfunction occurs early in the atherosclerotic disease process, often preceding clinical symptoms. Use of menopausal hormone treatment (MHT) to reduce cardiovascular risk is controversial. This study evaluated effects of 4 years of MHT on endothelial function in healthy, recently menopausal women. METHODS Endothelial function was determined by pulse volume digital tonometry providing a reactive hyperemia index (RHI) in a subset of women enrolled in the Kronos Early Estrogen Prevention Study. RHI was measured before and annually after randomization to daily oral conjugated equine estrogen (oCEE, 0.45 mg), weekly transdermal 17β-estradiol (tE2, 50 μg) each with intermittent progesterone (200 mg daily 12 days of the month) or placebo pills and patch. RESULTS At baseline, RHI averaged 2.39 ± 0.69 (mean ± standard deviation; n = 83), and over follow-up did not differ significantly among groups: oCEE, 2.26 ± 0.48 (n = 26); tE2, 2.26 ± 0.45 (n = 24); and placebo, 2.37 ± 0.37 (n = 33). Changes in RHI did not correlate with changes in traditional cardiovascular risk factors, but may inversely correlate with carotid intima medial thickness (Spearman correlation coefficient ρ = -0.268, p = 0.012). CONCLUSION In this 4-year prospective assessment of recently menopausal women, MHT did not significantly alter RHI when compared to placebo.