Comparison of tibolone and conjugated equine estrogens effects on carotid artery atherosclerosis of postmenopausal monkeys.
OBJECTIVE
Tibolone is a tissue-specific compound that has favorable effects on bone and menopausal symptoms without stimulating endometrium or breast, but lowers concentrations of plasma high-density lipoprotein (HDL) cholesterol (HDLC). This study was designed to determine whether the HDL lowering with tibolone exacerbated common or internal carotid artery atherosclerosis and to evaluate tibolone treatment relative to conjugated equine estrogens (CEE) alone or in combination with medroxyprogesterone acetate (MPA).


METHODS
Carotid artery atherosclerosis was compared in groups of surgically postmenopausal cynomolgus monkeys treated with CEE, CEE+MPA, or either of 2 doses of tibolone versus untreated monkeys.


RESULTS
Despite a 30% to 52% lowering of HDLC with tibolone, there was no significant effect on carotid artery atherosclerosis. CEE and CEE+MPA, however, inhibited carotid artery atherosclerosis by approximately 60%.


CONCLUSIONS
In surgically postmenopausal cynomolgus monkeys, CEE and CEE+MPA inhibited common and internal carotid artery atherosclerosis. Despite the potentially adverse effects of tibolone on HDLC, tibolone did not exacerbate atherosclerosis.
Clarkson
Thomas B
TB
Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA. tclarkso@wfubmc.edu
Anthony
Mary S
MS
Mikkola
Tomi S
TS
St Clair
Richard W
RW
D000818:Animals; D002340:Carotid Artery Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology; D002343:Carotid Artery, Internal / Q000187:drug effects / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D015243:Cholesterol, VLDL / Q000097:blood; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D018450:Disease Progression; D004359:Drug Therapy, Combination; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D008077:Lipoproteins, LDL / Q000097:blood; D008252:Macaca fascicularis; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D009652:Norpregnenes / Q000494:pharmacology*; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D013995:Time; D014654:Vascular Patency / Q000187:drug effects
D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D020847:Estrogen Receptor Modulators; D004966:Estrogens, Conjugated (USP); D008077:Lipoproteins, LDL; D009652:Norpregnenes; D017258:Medroxyprogesterone Acetate; C027385:tibolone