Serum cholesterol efflux potential in postmenopausal monkeys treated with tibolone or conjugated estrogens

Abstract

Tibolone is a synthetic steroid used for the treatment of climacteric symptoms and the prevention of osteoporosis, but the effect on the cardiovascular system is unclear since tibolone lowers high-density lipoprotein (HDL) levels. We investigated if long-term treatment with tibolone or conventional hormone replacement therapy (HRT) in cynomolgus monkeys could affect their serum cholesterol efflux potential. Surgically postmenopausal cynomolgus monkeys were treated for 2 years with conjugated equine estrogens (CEE), CEE plus medroxyprogesterone acetate (MPA), low-dose tibolone, or high-dose tibolone. Plasma lipid, lipoprotein, and apolipoprotein levels were monitored during the study. The cholesterol efflux potential of the serum from each animal was determined in (3)H-cholesterol-labeled Fu5AH cells and skin fibroblasts in culture. Tibolone induced a dose-dependent 30% to 52% reduction in HDL levels. When HDL concentrations were reduced by 30%, as seen in women, there was no reduction in the serum cholesterol efflux potential in Fu5AH cells. With a 52% reduction in HDL, there was a 14% reduction in cholesterol efflux. Although CEE or CEE+MPA had no significant effect on HDL levels, CEE treatment increased serum cholesterol efflux potential by 7%. With the same sera, no changes in cholesterol efflux were seen with fibroblasts. Although our findings suggest that HDL concentration is correlated with cholesterol efflux potential of serum, this relationship is weak, explaining only 16% of the variability. This is emphasized by the fact that despite a 30% lowering of HDL with tibolone, there was no indication of an adverse effect on cellular cholesterol efflux. Other changes in the serum not measured in this study must contribute significantly to the cholesterol efflux potential of serum. Because changes in cholesterol efflux potential of serum were seen only in Fu5AH cells, a cell line rich in SR-B1 receptors, this implies that the changes seen in this study were mediated largely by the SR-B1 pathway.