A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women: Effects on arterial compliance and endothelial function

Abstract

OBJECTIVE: To study the effects of long-term combined continuous oral hormone replacement therapy (HRT) on vascular function in healthy postmenopau-sal women. BACKGROUND: The cardiovascular effects of HRT are controversial. Improvement in vascular function is a proposed mechanism of oestrogen action but there are no long-term controlled human trials in this area. In this study, we examined the effects of HRT on lipid profiles and vascular function, encompassing both biomechanical arterial properties [systemic arterial compliance (SAC) and pulse wave velocity (PWV)] and endothelial function [flow-mediated vasodilation (FMD)]. METHODS: In this 2-year, double-blind, placebo-controlled study, 59 healthy postmenopausal women were randomized to oral combined continuous oes-trogen and progesterone [Kliogest®, oestradiol (2 mg), norethisterone (1 mg)] or placebo, with endpoints measured at baseline, 6 weeks and after 6, 12 and 24 months of treatment. RESULTS: Oral combined HRT reduced lipoprotein a [Lp(a)], although other lipid benefits were not observed. There were no significant changes in SAC, PWV or FMD with oral combined HRT, compared to placebo. CONCLUSION: In this long-term, randomized placebo-controlled trial, oral continuous HRT with combined oestradiol and norethisterone in healthy postmeno-pausal women did not improve a spectrum of indices of arterial function compared to placebo. These results suggest that HRT might not be of cardiovascular benefit in postmenopausal women.