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.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Koh
Kwang Kon
KK
Division of Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, Korea. kwangk@ghil.com
Han
Seung Hwan
SH
Shin
Mi-Seung
MS
Ahn
Jeong Yeal
JY
Lee
Yonghee
Y
Shin
Eak Kyun
EK
D001161:Arteriosclerosis / Q000097:blood / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage*; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage*; D011446:Prospective Studies; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D015415:Biomarkers; D008076:Cholesterol, HDL; D004338:Drug Combinations; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009652:Norpregnenes; D014280:Triglycerides; D011374:Progesterone; D002097:C-Reactive Protein; C027385:tibolone