Does the beneficial effect of HRT on endothelial function depend on lipid changes.
OBJECTIVE
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.
Ossewaarde
Marlies E
ME
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht HP D01.335, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
Bots
Michiel L
ML
van der Schouw
Yvonne T
YT
de Kleijn
Miriam J J
MJ
Wilmink
Hanneke W
HW
Bak
Annette A A
AA
Planellas
Juan
J
Banga
Jan Dirk
JD
Grobbee
Diederick E
DE
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008875:Middle Aged; D009652:Norpregnenes / Q000494:pharmacology*; D011673:Pulsatile Flow / Q000187:drug effects
D008078:Cholesterol, LDL; D004966:Estrogens, Conjugated (USP); D017270:Lipoprotein(a); D009652:Norpregnenes; D002784:Cholesterol; D017258:Medroxyprogesterone Acetate; C027385:tibolone