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Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux
Author(s) -
Von Eckardstein Arnold,
Crook David,
Elbers Jolanda,
Ragoobir Jennifer,
Ezeh Benjamin,
Helmond Frans,
Miller Norman,
Dieplinger Hans,
Bennink Herjan Coelingh,
Assmann Gerd
Publication year - 2003
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2003.01666.x
Subject(s) - endocrinology , medicine , tibolone , cholesterylester transfer protein , cholesterol , reverse cholesterol transport , chemistry , cholesteryl ester , lipoprotein , sphingomyelin , high density lipoprotein , apolipoprotein b , very low density lipoprotein , lipoprotein lipase , hepatic lipase , intermediate density lipoprotein , phospholipid transfer protein , phospholipid , biology , biochemistry , menopause , adipose tissue , membrane
Summary 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%), preβ‐LpA‐I (−10%) and α‐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.