Lipoprotein compositional changes with combination hormone therapy (conjugated estrogen and medroxyprogesterone) in African American women.

Objective: To determine whether combination hormone therapy (HT) significantly alters lipoprotein composition in healthy African American women.

Methods: Postmenopausal African American women, 45 to 65 years old, were randomly assigned to receive daily HT (conjugated equine estrogen, 0.625 mg, and medroxyprogesterone, 2.5 mg) or placebo (treated, 44; placebo, 16) for 12 weeks. Lipoproteins were separated by gradient ultracentrifugation into very-low-density, intermediate-density, and low-density lipoproteins (VLDL, IDL, and LDL) and 3 high-density lipoprotein (HDL) subfractions (light, medium, and dense--L, M, and D). Apolipoprotein (apo) A-I, A-II, C-III, C-II, and C-I were measured by high-performance liquid chromatography. Apo B, phospholipids, triglycerides, cholesterol, and free cholesterol were measured by standard assays.

Results: Total plasma cholesterol, triglycerides, LDL apo B, and total apo B did not change during HT. A small, transient reduction occurred in LDL cholesterol, and a persistent reduction was noted in VLDL apo B, apo C-II, and apo C-III. Total HDL phospholipids, cholesterol, apo A-I, and apo A-II increased, whereas the LDL/HDL ratio and the apo B/apo A-I ratio decreased. Cholesterol ester increased in both HDL-L and HDL-M, but only a transient increase occurred in HDL-L phospholipids. Apo A-I increased in HDL-L, HDL-M, and HDL-D; however, a similar increase occurred in HDL-D apo A-I in the control subjects. Moreover, an increase occurred in apo A-II in HDL-M. A reduction in the apo A-II:A-I ratio in HDL-L but not in HDL-M indicated an increase in HDL-L LpA-I particles. The increase in HDL particles in HDL-M was entirely due to an increase in LpA-I:A-II particles. Apo C-III increased in both HDL-L and HDL-M. The absence of changes in the HDL lipid ratios indicated an unaltered lipid composition of these particles. No changes were found in IDL compositional measurements. In 12 treated patients and 4 control subjects, Lp(a) was detected by ultracentrifugation; no changes were noted in Lp(a) composition or quantity with HT. Total Lp(a) measured by enzyme immunosorbent assay showed a trend toward an increase in treated patients after 12 weeks of HT.

Conclusions: African American women had a beneficial response to HT by increasing the number of LpA-I particles in HDL-L and LpA-I:A-II particles in HDL-M as well as cholesterol esters in both. There was a small reduction in VLDL apo B (and thus particle number) but only a transient reduction in LDL cholesterol. A shift of apo C-III from VLDL to HDL was noted. No detrimental changes occurred in any lipoprotein subfraction (specifically, no increase in triglycerides).