Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux.
OBJECTIVE
Androgens and other drugs that reduce plasma concentrations of high density lipoprotein (HDL) cholesterol are often considered to be pro-atherogenic. Tibolone lowers HDL-cholesterol by 20% but the clinical significance of this effect is unknown.


METHODS
In a randomized, double-blind study, 34 women received 2.5 mg tibolone daily and 34 women received placebo. Serum concentrations of lipids, lipoprotein subclasses and apolipoproteins, together with plasma activities of lipid transfer proteins and lipolytic enzymes and the capacity of plasma to induce cholesterol efflux from cultured cells, were measured.


RESULTS
Compared to placebo, tibolone reduced serum concentrations of HDL-cholesterol (-14%), HDL phosphatidylcholine (-14%), apolipoprotein (apo)A-I (-12%), HDL subclasses lipoprotein (Lp)A-I (-20%), HDL-apoE (-16%), pre beta-LpA-I (-10%) and alpha-LpA-I (-12%) and increased hepatic lipase activity (+25%) and HDL sphingomyelin : phosphatidylcholine ratio (10.5%), but did not alter serum concentrations of HDL sphingomyelin, apoA-IV and LpA-I/A-II, lipoprotein lipase, the plasma activities of lecithin : cholesterol acyl transferase, cholesteryl ester transfer protein, phospholipid transfer protein or the plasma capacity to release cholesterol from cultured fibroblasts or Fu5AH hepatocytes.


CONCLUSIONS
Tibolone lowers HDL-cholesterol in part by increasing hepatic lipase activity. Conservation of sphingomyelin and apoA-II in HDL, as well as cholesteryl ester transfer protein activity, preserves the capacity of plasma to release cholesterol, despite the lower concentrations of HDL-cholesterol. This may have important implications for the use of steroid effects on HDL concentrations as surrogates for atherosclerosis.
von Eckardstein
Arnold
A
Institüt für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität Münster, Germany. arnold.voneckardstein@ikc.usz.ch
Crook
David
D
Elbers
Jolanda
J
Ragoobir
Jennifer
J
Ezeh
Benjamin
B
Helmond
Frans
F
Miller
Norman
N
Dieplinger
Hans
H
Bennink
Herjan Coelingh
HC
Assmann
Gerd
G
D002352:Carrier Proteins / Q000097:blood; D018929:Cell Culture Techniques / Q000379:methods; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects*; D004311:Double-Blind Method; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008049:Lipase / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008875:Middle Aged; D009652:Norpregnenes / Q000494:pharmacology*
D002352:Carrier Proteins; D008076:Cholesterol, HDL; D020847:Estrogen Receptor Modulators; D008055:Lipids; D009652:Norpregnenes; C030363:lipid transfer protein; D002784:Cholesterol; D008049:Lipase; C027385:tibolone