Intranasal continuous combined 17β-estradiol/norethisterone therapy improves the lipid profile in healthy postmenopausal women

Objective: To compare the effects of continuous combined 17β-estradiol (E 2 ) plus norethisterone (acetate) [NET(A)] therapy by either intranasal or oral administration on the lipid profile in postmenopausal women. Design: Randomized, double-blind, multicenter trial. Setting: Gynecologic outpatient department. Patient(s): Two-hundred thirty-three healthy postmenopausal women. Intervention(s): Women received continuous combined hormone therapy, either intranasal E 2 /NET (175 μg/275 μg) as a spray (n = 117) or oral E 2 /NETA (1 mg/0.5 mg) as a capsule (n = 116), for 1 year. Main Outcome Measure(s): Fasting plasma concentrations of lipids and (apo)lipoproteins; and atherogenic indices at baseline and after 12, 24, and 52 weeks of treatment. Result(s): We found a significant (P<.001) decrease from baseline in both treatment groups in total, low-density lipoprotein- (LDL), high-density lipoprotein- (HDL), and HDL 2 -cholesterol, in triglycerides, apolipoprotein B (apoB), and lipoprotein(a). Levels of HDL 3 -cholesterol and apolipoprotein A1 (apoA1) were transiently decreased in the intranasal group. In the oral group, compared with the intranasal group, the decrease was larger for ratio total and LDL-cholesterol and lipoprotein(a) and smaller for triglycerides and apoA1. In the oral group, the ratios total/HDL cholesterol and LDL/HDL cholesterol were lowered, and the ratio apoB/LDL was increased, more than in the intranasal group. Conclusion(s): Both intranasal and oral E 2 /NET(A) therapy improved the lipid profile of healthy postmenopausal women, with some effects being more pronounced after oral administration.