Significant differential effects of lower doses of hormone therapy or tibolone on markers of cardiovascular disease in post-menopausal women: a randomized, double-blind, crossover study

Eur Heart J. 2005 Jul;26(14):1362-8. doi: 10.1093/eurheartj/ehi311. Epub 2005 May 4.

Abstract

Aims: We have previously reported that lower doses of hormone therapy (L-HT) and tibolone have different effects on markers of cardiovascular disease when compared with conventional doses of HT. The objective was to compare the effects of L-HT and tibolone on lipid profile, vasodilation, and factors associated with inflammation and haemostasis.

Methods and results: Forty-one women received a combination of micronized progesterone 100 mg with conjugated equine estrogen 0.3 mg vs. tibolone 2.5 mg alone daily in random order during 2 months with 2 months washout period. When compared with L-HT, tibolone significantly reduced total cholesterol (P<0.001), triglyceride (P<0.001), HDL cholesterol (P<0.001) levels, and triglyceride/HDL cholesterol ratios (P=0.004) except total cholesterol/HDL cholesterol ratios. Tibolone improved flow-mediated response to hyperaemia from baseline values (P<0.001) by a similar magnitude to L-HT. L-HT and tibolone did not increase high-sensitivity C-reactive protein relative to baseline values. L-HT reduced antithrombin III from baseline values (P=0.037), compared with tibolone showing no changes. However, there was no difference between either. In contrast, tibolone increased pro-thrombin fragment 1+2 (F1+2) from baseline values (P=0.002), compared with L-HT showing no changes. Tibolone significantly reduced plasma plasminogen activator inhibitor type 1 (PAI-1) antigen levels from baseline values (P=0.004), compared with L-HT showing no changes. The effects of L-HT and tibolone on F1+2 and PAI-1 were significantly different (P=0.045 and P=0.008, respectively).

Conclusion: Both tibolone and L-HT improved flow-mediated response by a similar magnitude and did not significantly increase high-sensitivity C-reactive protein. However, tibolone significantly reduced PAI-1, but increased F1+2 more than L-HT.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Arteriosclerosis / blood
  • Arteriosclerosis / prevention & control
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, HDL / blood
  • Cohort Studies
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Combinations
  • Estrogen Receptor Modulators / administration & dosage*
  • Estrogens / administration & dosage*
  • Female
  • Hemostasis / drug effects
  • Hormone Replacement Therapy / methods*
  • Humans
  • Middle Aged
  • Norpregnenes / administration & dosage*
  • Postmenopause
  • Progesterone / administration & dosage*
  • Prospective Studies
  • Triglycerides / blood
  • Vasodilation / drug effects

Substances

  • Biomarkers
  • Cholesterol, HDL
  • Drug Combinations
  • Estrogen Receptor Modulators
  • Estrogens
  • Norpregnenes
  • Triglycerides
  • Progesterone
  • C-Reactive Protein
  • tibolone