Multisystem evaluations of the long-term effects of tibolone on postmenopausal monkeys.
This long-term study (2 years) was designed to compare the effects of tibolone (LoTib at 0.05 mg/kg and HiTib at 0.2 mg/kg) with those of conjugated equine oestrogens (CEE) alone (0.042 mg/kg) and CEE continuously combined with medroxyprogesterone acetate (MPA) (0.167 mg/kg) on coronary artery atherosclerosis, bone, mammary gland and uterus in ovariectomised cynomolgus monkeys fed a moderately atherogenic diet. Despite reductions in plasma concentrations of high density lipoprotein cholesterol in tibolone-treated monkeys, there was no exacerbation of coronary artery atherosclerosis. Tibolone was equivalent to, or slightly better than, CEE and CEE + MPA in protecting against postmenopausal bone loss and loss of bone strength. Tibolone also resulted in less stimulation of breast and endometrial tissue compared with CEE and CEE + MPA. In conclusion, the results suggest that tibolone is a cardiovascular-safe treatment that is effective for the prevention of osteoporosis and that may have advantages over CEE or CEE + MPA with regard to endometrial and breast safety.
Clarkson
T B
TB
Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA. tclarkso@wfubmc.edu
Anthony
M S
MS
Cline
J M
JM
Lees
C J
CJ
Ederveen
A G H
AG
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000187:drug effects; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000187:drug effects; D008593:Menopause; D023421:Models, Animal; D009652:Norpregnenes / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D011897:Random Allocation; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D020845:Selective Estrogen Receptor Modulators; C027385:tibolone