HDL biology
Tibolone lowers HDL cholesterol by 14% via increased hepatic lipase activity, but preserves cholesterol efflux capacity without affecting CETP activity (Clin Endocrinol 2003)
Original title: Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux
In a randomized, double-blind study, 34 women received tibolone 2.5 mg daily and 34 received placebo. Compared with placebo, tibolone reduced serum HDL cholesterol (-14%), HDL phosphatidylcholine (-14%), apolipoprotein A-I (-12%), the HDL subclasses LpA-I (-20%), HDL-apoE (-16%), prebeta-LpA-I (-10%), and alpha-LpA-I (-12%), and increased hepatic lipase activity (+25%) and the HDL sphingomyelin-to-phosphatidylcholine ratio (10.5%), but did not alter HDL sphingomyelin, apoA-IV, lipoprotein lipase, lecithin:cholesterol acyltransferase, cholesteryl ester transfer protein (CETP), or phospholipid transfer protein activities, nor the plasma capacity to release cholesterol from cultured cells. Tibolone therefore lowers HDL cholesterol partly by increasing hepatic lipase activity, while conservation of sphingomyelin, apoA-II, and CETP activity preserves the plasma capacity to release cholesterol despite lower HDL cholesterol.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.