Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women

Abstract. Gužič‐Salobir B, Keber I, Seljeflot I, Arnesen H, Vrabič L (University Medical Centre, Ljubljana, Slovenia; Ullevaal University Hospital, Oslo, Norway; and Novo Nordisk A/S, Ljubljana, Slovenia). Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women. J Intern Med 2001; 250: 508–515. Objectives. Large scale epidemiological studies suggest that hormone replacement therapy (HRT) reduces cardiovascular events in postmenopausal women. Improvement in endothelial function may contribute to this protective effect. Design. In a prospective, double blind study, 61 healthy postmenopausal women were randomized to receive either oral continuous combined HRT [oestradiol 2 mg and norethisterone acetate (NETA) 1 mg per day] or placebo. Endothelial function, assessed by flow‐mediated vasodilation (FMD) of the brachial artery and expression of soluble endothelial cell adhesion molecules (CAM) were determined before, after 3 and 6 months of therapy. Results. The FMD was significantly improved in women on combined HRT (from 5.97% to 10.94% after 3 months and to 10.58% after 6 months; both P < 0.01 versus baseline values) and did not change in the placebo group (6.92% at baseline, 5.86% after 3 and 6.26% after 6 months). After 3 months of combined HRT, significant decreases of 24.6% for E‐selectin and 13.9% for intercellular adhesion molecule‐1 (ICAM‐1) were observed (both P < 0.01 versus baseline values) and were sustained after 6 months of therapy, whilst no differences emerged in the placebo group. Conclusions. Oestradiol and norethisterone acetate improve endothelial function by both enhancing FMD and reducing the levels of soluble E‐selectin and ICAM‐1 in healthy postmenopausal women.