Does the beneficial effect of HRT on endothelial function depend on lipid changes

Objectives: To determine whether improvement in endothelial function of the brachial artery observed in women treated with hormone replacement therapy (HRT) may be explained by changes in lipid profile or blood pressure, information was used obtained in a single-centre, randomised, double blind, placebo-controlled trial. Methods: Hundred-and-five healthy postmenopausal women, aged 50–65 years, were treated with 0.625 mg conjugated equine estrogens (CEE) combined with 2.5 mg medroxyprogesterone acetate (MPA) (CEE+MPA), 2.5 mg tibolone or placebo for 3 months. At baseline and after 3 months, endothelial function was assessed using flow-mediated dilatation (FMD) and nitro glycerine-mediated dilatation (NMD). Furthermore, lipids were measured. Multivariate linear regression analysis was applied to address the research question. Results: Treatment with CEE+MPA resulted in an improvement in FMD of 2.0% (95% CI: −0.1; 4.1). CEE/MPA reduced total cholesterol with 13% (95% CI: −18%; −7%), LDL-cholesterol with 23% (95% CI: −30%; −15%) and lipoprotein(a) (Lp(a)) with 14% (95% CI: −26%; −2%). The magnitude of the relation of CEE/MPA with endothelial function was attenuated to from 2.0 to 1.6% when change in Lp(a) was taken into account. Adjustments for other lipids or blood pressure did not attenuate the association. Conclusions: The improvement in endothelial function in postmenopausal women treated with CEE+MPA appears to be partially mediated by change in Lp(a), and apparently not by changes in other lipids.