title: Effects of tibolone or continuous combined oestradiol/norethisterone acetate on glucose and insulin metabolism.
abstract: OBJECTIVE
  To determine the effects of tibolone or oestradiol (E(2) )/norethisterone acetate (NETA) hormone replacement therapy on glucose and insulin metabolism in postmenopausal women.
  
  
  METHODS
  Single-centre double-blind placebo-controlled randomized clinical trial.
  
  
  METHODS
  We randomized 105 healthy postmenopausal women to tibolone 2·5 mg daily, continuous combined oral E(2)  2 mg/NETA 1 mg daily or placebo over a 2-year study. We performed intravenous glucose tolerance tests (IVGTT) with measurements of plasma glucose, insulin and C-peptide concentrations and the IVGTT glucose elimination rate, k. Mathematical modelling was performed to determine measures of insulin sensitivity, S(i) , pancreatic insulin secretion and hepatic and plasma insulin elimination.
  
  
  RESULTS
  Tibolone decreased S(i)  to 53-63% and k to 72-79% of baseline values but increased IVGTT phase 2 C-peptide concentrations 1·6-1·8-fold and pancreatic insulin secretion 2·2-2·4-fold, so overall IVGTT glucose concentrations were unaffected. Similar, but for k, significantly smaller changes in insulin and C-peptide secretion were seen with E(2) /NETA, also with no effect on overall IVGTT glucose concentrations.
  
  
  CONCLUSIONS
  Tibolone reduces insulin sensitivity. Healthy postmenopausal women seem able to compensate for this and maintain normal postload glucose concentrations, but it may not be advisable to prescribe tibolone to women with, or at increased risk for, diabetes.
authors: Goodrest Croft Surgery, Yardley Wood, London, UK.
authors: Nik
authors: N
authors: Manassiev
authors: Ian F
authors: IF
authors: Godsland
authors: Anthony J
authors: AJ
authors: Proudler
authors: Malcolm I
authors: MI
authors: Whitehead
authors: John C
authors: JC
authors: Stevenson
mesh_terms: D000368:Aged; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000494:pharmacology*; D009652:Norpregnenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D003280:Contraceptives, Oral, Synthetic; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D007328:Insulin; D009652:Norpregnenes; D004958:Estradiol; C027385:tibolone; D005947:Glucose; D009640:Norethindrone