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.
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: Garnet L Anderson; Marian Limacher; Annlouise R Assaf; Tamsen Bassford; Shirley A A Beresford; Henry Black; Denise Bonds; Robert Brunner; Robert Brzyski; Bette Caan; Rowan Chlebowski; David Curb; Margery Gass; Jennifer Hays; Gerardo Heiss; Susan Hendrix; Barbara V Howard; Judith Hsia; Allan Hubbell; Rebecca Jackson; Karen C Johnson; Howard Judd; Jane Morley Kotchen; Lewis Kuller; Andrea Z LaCroix; Dorothy Lane; Robert D Langer; Norman Lasser; Cora E Lewis; JoAnn Manson; Karen Margolis; Judith Ockene; Mary Jo O'Sullivan; Lawrence Phillips; Ross L Prentice; Cheryl Ritenbaugh; John Robbins; Jacques E Rossouw; Gloria Sarto; Marcia L Stefanick; Linda Van Horn; Jean Wactawski-Wende; Robert Wallace; Sylvia Wassertheil-Smoller Journal: JAMA Date: 2004-04-14 Impact factor: 56.272
Authors: Rowan T Chlebowski; Susan L Hendrix; Robert D Langer; Marcia L Stefanick; Margery Gass; Dorothy Lane; Rebecca J Rodabough; Mary Ann Gilligan; Michele G Cyr; Cynthia A Thomson; Janardan Khandekar; Helen Petrovitch; Anne McTiernan Journal: JAMA Date: 2003-06-25 Impact factor: 56.272
Authors: Thomas B Clarkson; Kelly F Ethun; Nicholas M Pajewski; Debbie Golden; Edison Floyd; Susan E Appt Journal: Menopause Date: 2014-01 Impact factor: 2.953
Authors: Kathleen M Eyster; Susan Appt; Abha Chalpe; Connie J Mark-Kappeler; Thomas C Register; Thomas B Clarkson Journal: Menopause Date: 2014-02 Impact factor: 2.953
Authors: Mei-Lyn Ong; Peck Yean Tan; Julia L MacIsaac; Sarah M Mah; Jan Paul Buschdorf; Clara Y Cheong; Walter Stunkel; Louiza Chan; Peter D Gluckman; Keefe Chng; Michael S Kobor; Michael J Meaney; Joanna D Holbrook Journal: G3 (Bethesda) Date: 2014-05-08 Impact factor: 3.154