Raloxifene, conjugated oestrogen and endothelial function in postmenopausal women.
OBJECTIVE
To study the long-term effects of raloxifene, a potential designer oestrogen, and oestrogen monotherapy on endothelial function in healthy postmenopausal women.


METHODS
A 2-year double-blind, randomized and placebo-controlled study in an Academic Medical Center. Fifty-six hysterectomized but otherwise healthy postmenopausal women randomly received raloxifene hydrochloride 60 mg day-1 (n = 15) or 150 mg day-1 (n = 13), conjugated equine oestrogen (CEE) 0.625 mg day-1 (n = 15), or placebo (n = 13).


METHODS
Endothelial function as estimated from brachial artery flow-mediated, endothelium-dependent vasodilation and nitroglycerine-induced endothelium-independent vasodilation, and plasma levels of the endothelium-derived regulatory proteins, von Willebrand factor (vWF) and endothelin (ET).


RESULTS
Raloxifene 60 mg did not significantly affect endothelial function. As compared with placebo, at 6 months of therapy, raloxifene 150 mg and CEE were associated with a mean increase in vWF of 25.5% point (95% CI 3.6-47.3) and 26.6% point (95% CI 6.9-46.3), respectively. At 24 months of therapy, raloxifene 150 mg was associated with a mean decrease in ET of 0.96 pg mL-1 (95% CI -1.57 to -0.36). Raloxifene nor CEE significantly affected endothelium-dependent and/or -independent vasodilation.


CONCLUSIONS
Our results suggest that long-term therapy with raloxifene or oral CEE does not affect endothelium-dependent vasodilation in healthy postmenopausal women. Raloxifene 150 mg day-1 might have both positive and negative effects on endothelium. The clinical significance of these findings remains to be investigated.
Duschek
E J J
EJ
Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
Stehouwer
C D A
CD
de Valk-de Roo
G W
GW
Schalkwijk
C G
CG
Lambert
J
J
Netelenbos
C
C
D000704:Analysis of Variance; D001916:Brachial Artery; D015198:Designer Drugs / Q000008:administration & dosage / Q000494:pharmacology; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014652:Vascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D014841:von Willebrand Factor / Q000032:analysis
D015198:Designer Drugs; D019040:E-Selectin; D020845:Selective Estrogen Receptor Modulators; D014841:von Willebrand Factor; D020849:Raloxifene Hydrochloride