Low dose estrogens inhibit coronary artery atherosclerosis in postmenopausal monkeys.
OBJECTIVE
To determine if low dose conjugated equine estrogens (CEE) result in a reduction of coronary artery atherosclerosis progression, and to relate these findings to previous studies using the traditional dose.


METHODS
Adult female monkeys (Macaca fascicularis) were fed an atherogenic diet for 10 months, to induce fatty streaks and small plaques comparable to those present in early postmenopausal women, and then ovariectomized and treated orally with: CEE (0.30 mg/day women's equivalent dose, n=28) or placebo (n=25) daily for 24 months. Body weight and estradiol were measured at 3, 6, 12 and 18 months and plasma lipids were measured at baseline and every 6 months.


RESULTS
Despite the lack of effect on plasma lipid profiles, monkeys treated with low dose CEE had marked reductions in coronary artery atherosclerosis plaque extent (intimal area) in all three main coronary arteries: left anterior descending artery (52% less, 0.044 mm(2) versus 0.091 mm(2), p=0.04); left circumflex artery (62% less, 0.045 mm(2) versus 0.119 mm(2), p=0.006) and right circumflex artery (42% less, 0.018 mm(2) versus 0.031 mm(2), p=0.20). The overall mean coronary atherosclerosis extent was 52% lower in CEE treated animals (0.042 mm(2) versus 0.088 mm(2), p=0.02).


CONCLUSIONS
Low dose CEE (0.30 mg/woman/day equivalent) was effective in reducing coronary atherosclerosis and the magnitude of the protection was comparable to previously reported studies using doses equivalent to 0.625 mg/woman/day. This study provides an experimental basis for the assumption that low dose CEE may be as effective as the traditional dose in inhibiting coronary atherosclerosis progression in early postmenopausal subjects.
Appt
Susan E
SE
Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC, United States. sappt@wfubmc.edu <sappt@wfubmc.edu>
Clarkson
Thomas B
TB
Lees
Cynthia J
CJ
Anthony
Mary S
MS
D000818:Animals; D003324:Coronary Artery Disease / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects*; D004036:Diet, Atherogenic; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008252:Macaca fascicularis; D010052:Ovariectomy; D017698:Postmenopause; D016896:Treatment Outcome
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D008055:Lipids; D008074:Lipoproteins; D004958:Estradiol