title: Effect of raloxifene and hormone therapy on serum markers of brain and whole-body cholesterol metabolism in postmenopausal women.
abstract: OBJECTIVE
  To compare the 2-year effects of raloxifene (Rlx) with oral postmenopausal hormone therapy (HT) on serum markers of brain and whole-body cholesterol metabolism.
  
  
  METHODS
  In a randomized, double-blind, placebo-controlled trial, 95 healthy, non-hysterectomized, early postmenopausal women received either daily Rlx 60 mg (n = 24), Rlx 150 mg (n = 23), HT (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 2.5 mg; n = 24), or placebo (n = 24). Fasting blood samples were collected at baseline and after 6, 12, and 24 months of treatment for measurement of serum concentrations of cholesterol by means of gas-liquid chromatography; 24S-hydroxycholesterol (cerebrosterol), lathosterol, and the plant sterol campesterol by means of gas-liquid chromatography-mass spectrometry. The analyses were performed retrospectively from serum samples stored at -70 degrees C for 5 years.
  
  
  RESULTS
  Twenty-four months of treatment with raloxifene 150 mg was associated with a significant reduction in serum cholesterol concentrations (-10%, P = 0.007). The ratio of 24S-hydroxycholesterol to cholesterol, a serum marker of brain cholesterol metabolism, showed a significant increase after 6 and 12 months with raloxifene 150 mg but not after 24 months (P = 0.001). The ratio of lathosterol to cholesterol, a marker of whole-body cholesterol synthesis, increased with raloxifene 60 mg (P = 0.163), raloxifene 150 mg (P < 0.001), as well as with HT (P = 0.005). The ratio of campesterol to cholesterol, a marker of cholesterol absorption rate, was significantly reduced with HT (P = 0.002).
  
  
  CONCLUSIONS
  Two-year treatment with raloxifene or HT had no influence on brain cholesterol metabolism, while whole-body cholesterol synthesis, assessed by the ratio of lathosterol to cholesterol, increased during raloxifene and HT.
authors.affiliation: Department of Obstetrics and Gynecology, Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Tatjana E
authors.initials: TE
authors.lastname: Vogelvang
authors.forename: Velja
authors.initials: V
authors.lastname: Mijatovic
authors.forename: Marius J
authors.initials: MJ
authors.lastname: van der Mooren
authors.forename: Ursula
authors.initials: U
authors.lastname: Pinsdorf
authors.forename: Klaus
authors.initials: K
authors.lastname: von Bergmann
authors.forename: J Coen
authors.initials: JC
authors.lastname: Netelenbos
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004966:Estrogens, Conjugated (USP); D006888:Hydroxycholesterols; D020845:Selective Estrogen Receptor Modulators; C044563:24-hydroxycholesterol; D020849:Raloxifene Hydrochloride; D002784:Cholesterol; D017258:Medroxyprogesterone Acetate