title: Effect of tibolone on turnover of cholesterol to bile acids in ovariectomized rats.
abstract: OBJECTIVE
  Tibolone is used in breast cancer therapy in women. The most important aspect of this therapy concerns its influence on bone and lipid metabolism. Several studies have reported the effect of tibolone on plasma lipids. Approximately 40% of total cholesterol removal occurs by its conversion to bile acids, a process that takes place in the liver. The aim of the study was to evaluate the influence of tibolone on the conversion of cholesterol to bile acids in estrogen-deficient rats.
  
  
  METHODS
  Thirty female Wistar rats were divided into three groups: sham-operated controls, ovariectomized controls, and ovariectomized rats treated with tibolone. After 42 days of drug administration, bile was collected under anesthesia after administration of radioactive 4-C cholesterol. Bile was assayed for total C radioactivity; C bile acids were determined after thin-layer chromatography separation by using the isotopic technique.
  
  
  RESULTS
  The ovariectomy decreased the concentrations of C-radioactive bile, taurocholic acid, and cholic acid. The administration of tibolone significantly increased the excretion of C-radioactive bile and C-radioactive bile acids as compared with ovariectomized controls. Moreover, the therapy with tibolone significantly increased the concentrations of C taurocholic acid, C glycocholic acid, cholic acid, and taurochenodeoxycholic plus taurodeoxycholic acids.
  
  
  CONCLUSIONS
  The results of the present study suggest that tibolone may increase the concentrations of cholesterol and trihydroxy bile acids in bile. These changes may be associated with an increased risk of gallstone generation.
authors.affiliation: Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Bogusław
authors.initials: B
authors.lastname: Czerny
authors.forename: Maria
authors.initials: M
authors.lastname: Teister
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Juzyszyn
authors.forename: Zofia
authors.initials: Z
authors.lastname: Mysliwiec
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlik
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000378:metabolism*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D002784:Cholesterol; C027385:tibolone