Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women.
BACKGROUND
Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus.


OBJECTIVE
To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT).


METHODS
Double-blind, randomized, parallel trial.


METHODS
Eight sites in the United States.


METHODS
390 healthy postmenopausal women recruited by advertisement.


METHODS
Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo.


METHODS
Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment.


RESULTS
At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P < .001), similar to the 14% reduction with HRT (P < .001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P < .001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL2-C) by 15% to 17% (P < .05), less than the 33% increase with HRT (P < .001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P < .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P < .001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2.


CONCLUSIONS
Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL2-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.
Walsh
B W
BW
Brigham and Women's Hospital, Boston, Mass 02115, USA. bwwalsh@bics.bwh.harvard.edu
Kuller
L H
LH
Wild
R A
RA
Paul
S
S
Farmer
M
M
Lawrence
J B
JB
Shah
A S
AS
Anderson
P W
PW
D000368:Aged; D000704:Analysis of Variance; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004967:Estrogens / Q000819:agonists*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D017698:Postmenopause; D045167:Progesterone Congeners / Q000627:therapeutic use; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride; D012307:Risk Factors
D001779:Blood Coagulation Factors; D004965:Estrogen Antagonists; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D008074:Lipoproteins; D010880:Piperidines; D045167:Progesterone Congeners; D020849:Raloxifene Hydrochloride; D017258:Medroxyprogesterone Acetate