title: Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL cholesterol, HDL particle concentration, and HDL function.
abstract: BACKGROUND
  Mifepristone is a glucocorticoid and progestin antagonist under investigation for the treatment of Cushing's syndrome. Mifepristone decreases high-density lipoprotein (HDL) cholesterol (HDL-C) levels in treated patients, but the clinical significance of this is unclear because recent studies suggest that functional properties of HDL predict cardiovascular disease status better than does HDL-C concentration.
  
  
  OBJECTIVE
  The aim of the study was to characterize the impact of mifepristone administration on HDL particle concentration and function.
  
  
  METHODS
  We conducted a double-blind, randomized, placebo-controlled trial at a single-site, clinical research center.
  
  
  METHODS
  Thirty healthy postmenopausal female volunteers participated in the study.
  
  
  METHODS
  Individuals were randomized to receive daily oral mifepristone (600 mg) or placebo for 6 wk.
  
  
  METHODS
  We measured HDL-C, serum HDL particle concentration, and HDL-mediated cholesterol efflux by treatment group.
  
  
  RESULTS
  As expected, ACTH, cortisol, estradiol, and testosterone levels increased in the mifepristone group. Mifepristone treatment decreased HDL-C and HDL particle concentration by 26 and 25%, respectively, but did not alter pre-β HDL concentration. In contrast, the serum HDL-mediated cholesterol efflux decreased with mifepristone treatment by only 12%, resulting in an effective increase of the efflux capacity per HDL particle. No changes were observed in cholesterol ester transfer protein or lecithin:cholesterol acyltransferase activity.
  
  
  CONCLUSIONS
  Treatment with mifepristone reduced HDL-C, HDL particle concentration, and serum HDL cholesterol efflux in postmenopausal women. However, on a per particle basis, the efflux capacity of serum HDL increased. These observations support the concept that a decrease in HDL-C may not represent proportional impairment of HDL function.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington 98195, USA. page@u.washington.edu
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.forename: Coleman
authors.initials: C
authors.lastname: Gross
authors.forename: Brian
authors.initials: B
authors.lastname: Ishida
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
authors.forename: Chongren
authors.initials: C
authors.lastname: Tang
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schaefer
authors.forename: Cheryl J
authors.initials: CJ
authors.lastname: Cox
authors.forename: John
authors.initials: J
authors.lastname: Kane
authors.forename: Jonathan Q
authors.initials: JQ
authors.lastname: Purnell
authors.forename: Richard L
authors.initials: RL
authors.lastname: Weinstein
authors.forename: Tomáš
authors.initials: T
authors.lastname: Vaisar
mesh_terms: D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology*; D017698:Postmenopause; D011374:Progesterone / Q000037:antagonists & inhibitors*
chemical_list: D008076:Cholesterol, HDL; D006727:Hormone Antagonists; D008075:Lipoproteins, HDL; D015735:Mifepristone; D011374:Progesterone