Continuous combined and sequential estradiol and norethindrone acetate treatment of postmenopausal women: effect of plasma lipoproteins in a two-year placebo-controlled trial

Our purpose was to examine the effects of postmenopausal estrogen therapy supplemented with progestogen on plasma lipoprotein levels.One hundred thirteen women were randomized to receive either placebo or a combination of 17 beta-estradiol and norethindrone acetate administered continuously (Kliogest) or sequentially (Trisequens). Plasma lipoprotein levels were measured at baseline and after 2 years of treatment and compared by analysis of variance.Hormone therapy lowered plasma cholesterol levels (p0.001) and low-density lipoprotein cholesterol (Kiogest, p0.001; Trisequens, p0.01), whereas high-density lipoprotein cholesterol levels were unchanged (Trisequens) or reduced (Kliogest, p0.01), primarily because of a decrease in the high-density lipoprotein-2 subfraction (p0.05). Low-density lipoprotein/high-density lipoprotein cholesterol ratios remained unchanged.Although hormonal replacement therapy with estradiol combined with norethindrone acetate eliminated the increase in high-density lipoprotein cholesterol levels observed with estrogen monotherapy, the reductions in low-density lipoprotein cholesterol concentrations still suggest reduced cardiovascular risk, according to the National Cholesterol Education Program and to recent observations indicating that risk is not necessarily inversely proportional to high-density lipoprotein cholesterol levels.