Sequential estrogen-progestin replacement therapy in healthy postmenopausal women: effects on cholesterol efflux capacity and key proteins regulating high-density lipoprotein levels.

Thirty healthy postmenopausal women were randomized into 2 groups that received a sequential combined hormone-replacement therapy (HRT) (n = 18; conjugated equine estrogen 0.625 mg/d for 28 days and 5 mg of medroxyprogesterone acetate during the last 14 days) or placebo (n = 12). Plasma samples were collected before and during treatment (days 0, 15, 43, 71). High-density lipoprotein (HDL) lipid content, lipoprotein (Lp)A-I and LpA-I:LpA-II concentration, lecithin:cholesterol acyl transferase activity (LCAT), phospholipid transfer protein (PLTP) activity, and the plasma capacity to carry out cholesterol efflux from Fu5AH cells were measured. Most significant changes were found within the first 15 days after HRT. After 71 days of HRT, we found an increase in LpA-I lipoparticles (27%) and the following HDL lipids: phospholipids (21%), triglycerides (45%), and free cholesterol (43%), as well as an increase in cholesterol efflux (12.5%). PLTP activity, on the other hand, decreased 21% after 71 days of treatment. No significant changes in LCAT activity, HDL-cholesterol ester or LpA-I:LpA-II particles were found. Positive correlation between cholesterol efflux and the variables LpA-I and HDL-phospholipids were observed. PLTP was negatively correlated with apolipoprotein (apo) A-I, LpA-I, and LpA-I:LpA-II. In summary, our study, performed during 3 hormonal cycles, shows that HRT not only modifies HDL-cholesterol level, but also its lipid composition and HDL lipoparticle distribution. HRT enhances the plasma capacity to carry out cholesterol efflux from the Fu5AH system and decreases the activity of PLTP, a key protein regulating HDL levels. Considering the protocol sampling, these results represent mainly the estrogenic effect of HRT.