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Raloxifene reduces atherosclerosis: studies of optimized raloxifene doses in ovariectomized, cholesterol‐fed rabbits
Author(s) -
Bjarnason Nina Hannover,
Haarbo Jens,
Byrjalsen Inger,
Kauffman Raymond F.,
Knadler Mary Pat,
Christiansen Claus
Publication year - 2000
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2000.00919.x
Subject(s) - raloxifene , ovariectomized rat , endocrinology , medicine , selective estrogen receptor modulator , placebo , cholesterol , estrogen , chemistry , estrogen receptor , pathology , alternative medicine , cancer , breast cancer
OBJECTIVE We have previously shown that raloxifene, a selective oestrogen receptor modulator, 35 mg/day inhibits atherosclerosis in ovariectomized, cholesterol‐fed rabbits. This effect was only partial as compared to 17β‐oestradiol 4 mg/day; however, plasma raloxifene concentrations were low relative to those obtained in raloxifene‐treated women. We therefore investigate the effects of raloxifene at higher doses. DESIGN The study on atherosclerosis in ovariectomized, cholesterol‐fed rabbits ( n = 80) compared raloxifene 70 mg/day and 210 mg/day to 17β‐oestradiol 4 mg/day and placebo. RESULTS After 48 weeks of therapy, the aortic cholesterol content in the 70 mg/day and 210 mg/day raloxifene treatment groups were 471 ± 56 nmol/mg protein and 456 ± 56 nmol/mg protein, respectively. This was significantly less than in the placebo group (654 ± 69 nmol/mg protein; P < 0.05). In the oestrogen‐treated group, the aortic cholesterol content was 357 ± 62 nmol/mg protein ( P < 0.01 as compared to placebo). Differences in serum lipids between the treatment groups could only partly explain the effect on aortic cholesterol content, indicating that additional anti‐atherogenic mechanisms may contribute to the decrease in aortic atherosclerosis. This anti‐atherosclerotic activity of raloxifene was observed at plasma concentrations comparable to those in postmenopausal women during raloxifene treatment. CONCLUSIONS We conclude that clinically relevant raloxifene treatment inhibits aortic atherosclerosis in ovariectomized, cholesterol‐fed rabbits.