title: Effects of bazedoxifene alone and with conjugated equine estrogens on coronary and peripheral artery atherosclerosis in postmenopausal monkeys.
abstract: OBJECTIVE
  The objectives of this study were to evaluate the effects of bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, on coronary and peripheral artery atheroscleroses and to determine if it would antagonize the atheroprotective effects of conjugated equine estrogens (CEE) on a monkey model.
  
  
  METHODS
  Ninety-eight surgically postmenopausal monkeys (Macaca fascicularis) were fed a moderately atherogenic diet and randomized to receive no treatment or women's equivalent doses of BZA (20 mg/d), CEE (0.45 mg/d), or BZA + CEE. The experimental period lasted for 20 months (equivalent to approximately 5 y in humans) during which interim measures of cardiovascular risk factors were made. At the end of the experimental period, the extent and severity of coronary and iliac artery atheroscleroses were quantified.
  
  
  RESULTS
  Body weight, adiposity, fasting glucose concentrations, and plasma lipid profiles were not different among treatment conditions. BZA had no adverse effects on the extent or severity of coronary or common iliac artery atherosclerosis when compared with no treatment. CEE, administered soon after inducing menopause, had robust atheroprotective effects on both the extent and the severity of iliac and coronary artery atheroscleroses. The addition of BZA to CEE treatment antagonized the atheroprotective effects of CEE.
  
  
  CONCLUSIONS
  In this nonhuman primate trial, treatment with BZA alone, CEE alone, and combined BZA and CEE does not have significant effects on plasma lipid profiles. CEE markedly inhibits the progression and complications of both coronary and iliac artery atheroscleroses. BZA has no adverse effects on atherosclerosis but attenuates the atheroprotective effects of CEE.
authors: Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157-1040, USA. tclarkso@wakehealth.edu
authors: Thomas B
authors: TB
authors: Clarkson
authors: Kelly F
authors: KF
authors: Ethun
authors: Haiying
authors: H
authors: Chen
authors: Debbie
authors: D
authors: Golden
authors: Edison
authors: E
authors: Floyd
authors: Susan E
authors: SE
authors: Appt
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D001786:Blood Glucose / Q000032:analysis; D050071:Bone Density Conservation Agents; D003324:Coronary Artery Disease / Q000473:pathology / Q000517:prevention & control*; D004036:Diet, Atherogenic; D004347:Drug Interactions; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D007083:Iliac Artery / Q000473:pathology; D007211:Indoles / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D008252:Macaca fascicularis; D010052:Ovariectomy; D017698:Postmenopause; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D050071:Bone Density Conservation Agents; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D008055:Lipids; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene