Effects of raloxifene and hormone replacement therapy on markers of serum atherogenicity in healthy postmenopausal women.
OBJECTIVE
To determine the effect of raloxifene (RLX) and hormone replacement therapy (HRT) on non-high density lipoprotein cholesterol (non-HDL-C) levels and the apolipoprotein-B/apolipoprotein-A1 (apo-B/apo-A1) concentration ratio, markers of serum atherogenicity, in postmenopausal women.


METHODS
Three hundred and ninety healthy postmenopausal women aged 45-72 years were enrolled in a double-blind, randomized, placebo-controlled, parallel trial at eight outpatient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), 60 or 120 mg/day raloxifene, or placebo for 6 months. Serum concentrations of non-HDL cholesterol and the apo-B/apo-A1 concentration ratio were measured in serum samples obtained at baseline and at 6 months of treatment.


RESULTS
At 6 months, non-HDL-C and apo-B/apo-A1 were significantly reduced by 60 mg/day RLX (10 and 11%, respectively), 120 mg/day RLX (9 and 12%, respectively) and HRT (10 and 12%, respectively), compared with placebo. The effect of all treatments to lower non-HDL-C and apo-B/apo-A1 was greatest in women with hypercholesterolemia (total-C>240 mg/dl) at baseline. Among women with undesirable (>160 mg/dl) non-HDL cholesterol at baseline, RLX and HRT lowered the percentage of these women remaining above this threshold after 6 months (placebo, 89%; 60 mg/day RLX, 61%; 120 mg/day RLX, 74%; HRT, 58%). Similar results were observed for women with high (>190 mg/dl) non-HDL cholesterol at baseline.


CONCLUSIONS
In healthy postmenopausal women, RLX and HRT lower serum non-HDL-C and apo-B/apo-A1, indicators of serum atherogenicity, to a similar extent.
Anderson
P W
PW
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. anderson_pamela_w@lilly.com
Cox
D A
DA
Sashegyi
A
A
Paul
S
S
Silfen
S L
SL
Walsh
B W
BW
D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects*; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D017698:Postmenopause; D045167:Progesterone Congeners / Q000008:administration & dosage; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014481:United States
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D002784:Cholesterol; D017258:Medroxyprogesterone Acetate