A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women: effects on arterial compliance and endothelial function.
OBJECTIVE
To study the effects of long-term combined continuous oral hormone replacement therapy (HRT) on vascular function in healthy postmenopausal 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 oestrogen and progesterone [Kliogest, oestradiol (2 mg), norethisterone (1 mg)] or placebo, with end-points 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.


CONCLUSIONS
In this long-term, randomized placebo-controlled trial, oral continuous HRT with combined oestradiol and norethisterone in healthy postmenopausal 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.
Teede
H J
HJ
Department of Medicine, Monash University, Dandenong Hospital, Victoria, Australia. h.teede@southernhealth.org.au
Liang
Y L
YL
Kotsopoulos
D
D
Zoungas
S
S
Cravent
R
R
McGrath
B P
BP
D000704:Analysis of Variance; D004311:Double-Blind Method; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage*; D004964:Estriol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000032:analysis; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D017698:Postmenopause; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D004338:Drug Combinations; D017270:Lipoprotein(a); D004958:Estradiol; C032040:Trisequens; D004964:Estriol; D009640:Norethindrone