Significant differential effects of hormone therapy or tibolone on markers of cardiovascular disease in postmenopausal women: a randomized, double-blind, placebo-controlled, crossover study.
OBJECTIVE
The objective was to compare the effects of tibolone and hormone therapy (HT) on lipid profile, vasodilation, and factors associated with inflammation and hemostasis.


RESULTS
Fifty-three women received micronized progesterone (MP, 100 mg) with conjugated equine estrogen (CEE, 0.625 mg) or tibolone (2.5 mg) daily for 2 months, with a 2-month washout period. Compared with HT, tibolone significantly reduced total cholesterol (P<0.001), triglyceride (P<0.001), and HDL cholesterol (P<0.001) levels as well as triglyceride/HDL cholesterol ratios (P<0.001) but not LDL cholesterol levels. Tibolone significantly improved flow-mediated brachial artery dilator response to hyperemia from baseline values (P<0.001) by a magnitude similar to that found with HT (P=0.628). Compared with tibolone, which showed no changes, HT significantly increased high-sensitivity C-reactive protein (hsCRP, P=0.030) and reduced antithrombin III (P<0.001). HT and tibolone significantly increased prothrombin fragment 1+2 (F1+2) from baseline values (P<0.001 and P=0.004, respectively). The effects of HT and tibolone on hsCRP, antithrombin III, and F1+2 were significantly different. HT and tibolone significantly reduced plasma levels of plasminogen activator inhibitor type 1 antigen from baseline levels (P=0.006 and P=0.005, respectively) to a similar degree (P=0.988).


CONCLUSIONS
Tibolone significantly improved flow-mediated brachial artery dilator response by a magnitude similar to that found with CEE+MP; however, tibolone did not significantly change hsCRP and antithrombin III, and tibolone increased F1+2 less than did CEE+MP.
Koh
Kwang Kon
KK
Division of Cardiology, Gil Heart Center, Gachon Medical School, Namdong-gu, Incheon, Korea. kwangk@ghil.com
Ahn
Jeong Yeal
JY
Jin
Dong Kyu
DK
Yoon
Byung-Koo
BK
Kim
Hyung Sik
HS
Kim
Dae Sung
DS
Kang
Woong Chol
WC
Han
Seung Hwan
SH
Choi
In Suck
IS
Shin
Eak Kyun
EK
D000990:Antithrombin III / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate; D008875:Middle Aged; D009652:Norpregnenes / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation
D015415:Biomarkers; D020847:Estrogen Receptor Modulators; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D014280:Triglycerides; D011374:Progesterone; D000990:Antithrombin III; D002097:C-Reactive Protein; D002784:Cholesterol; D017258:Medroxyprogesterone Acetate; C027385:tibolone