A comparison of tibolone and hormone replacement therapy on coronary artery and myocardial function in ovariectomized atherosclerotic monkeys.
OBJECTIVE
Tibolone is used to prevent osteoporosis and to treat climacteric symptoms. The objectives of these studies were to measure and compare the effects of tibolone with hormone replacement therapy on coronary artery vascular reactivity and myocardial function and to relate these outcomes to treatment-induced plasma lipid/lipoprotein concentrations and atherosclerosis.


METHODS
One hundred forty-eight adult ovariectomized cynomolgus monkeys were fed an atherogenic diet for 24 months while receiving one of five oral treatments: no treatment (control, n = 31); conjugated equine estrogens (CEE), given at the equivalent of 0.625 mg/day ( n = 27); CEE (same dose) plus medroxyprogesterone acetate (MPA), given at the equivalent of 2.5 mg/day ( n = 29); low-dose tibolone (LoTib; 0.625 mg/day equivalent, n = 30); or high-dose tibolone (HiTib; 2.5 mg/day equivalent, n = 31).


RESULTS
Quantitative coronary angiography showed that endothelium-mediated dilation was enhanced (17.5 +/- 5%, p = 0.002) in the CEE-treated group (but not other treatment groups) compared with the control. Both doses of tibolone and CEE reduced the incidence of dobutamine-induced ST-segment depression (LoTib: 33%, HiTib 25%, and CEE: 23%) compared to the control (79%) ( p = <0.05). Neither vascular reactivity nor dobutamine-induced myocardial ischemia were associated with treatment-induced changes in atherosclerosis or plasma lipid/lipoprotein concentrations.


CONCLUSIONS
Tibolone, unlike CEE, has no benefit for endothelium-mediated dilation. Despite these differences, both tibolone and CEE reduced the incidence of myocardial ischemia, whereas CEE+MPA had no effect. It is speculated that tibolone may have direct effects on the myocardium that protect against myocardial ischemia.
Williams
J Koudy
JK
The Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA. kwilliam@wfubmc.edu
Hall
Jason
J
Anthony
Mary S
MS
Register
Thomas C
TC
Reis
Steven E
SE
Clarkson
Thomas B
TB
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000188:drug therapy; D004280:Dobutamine / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004966:Estrogens, Conjugated (USP) / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D007262:Infusions, Intravenous; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008252:Macaca fascicularis; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000188:drug therapy; D009652:Norpregnenes / Q000097:blood / Q000494:pharmacology*; D010052:Ovariectomy
D020847:Estrogen Receptor Modulators; D004966:Estrogens, Conjugated (USP); D008074:Lipoproteins; D009652:Norpregnenes; D004280:Dobutamine; D017258:Medroxyprogesterone Acetate; C027385:tibolone