Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow

Abstract 

Objectives

To evaluate the lipid profile, insulin resistance and vasomotricity, and the interaction between these factors, in postmenopausal women receiving hormone therapy.

Methods

A prospective, randomized, double-blind study was carried out in which 77 postmenopausal women received one of the three treatment regimens: (A) 2mg oral micronized estradiol (E₂) (n=25); (B) 2mg oral E₂+1mg oral norethisterone acetate (NETA) (n=28); or C) placebo (n=24), daily for 6 months. Evaluations were carried out at baseline and at the end of treatment on lipid and lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and pulsatility index (PI) of the internal carotid artery by Doppler ultrasonography.

Results

Mean increases of 15.6% and 2.4% and a reduction of 6.4% in high-density lipoprotein (HDL) levels were found for the E₂, E₂+NETA and placebo groups, respectively. Reductions of 9.5% and 3.7% and an increase of 12.1% in low-density lipoprotein (LDL), and reductions of 20.0% and 3.8% and an increase of 28.8% in the LDL:HDL ratio were found for the E₂, E₂+NETA and placebo groups, respectively (p<0.001 in all cases). Insulin levels and HOMA-IR decreased 12.8% and 12.3% in the E₂ group and increased 12.9% and 16.0% in the E₂+NETA group (p<0.05), respectively. Carotid PI following treatment was 1.18±0.23, 1.38±0.20 and 1.41±0.21 for the E₂, E₂+NETA and placebo groups, respectively (p=0.0006).

Conclusions

Oral estrogen therapy led to an improvement in lipid profile, insulin resistance and carotid blood flow, which was cancelled when NETA was associated.

Keywords: Hormone therapy, Estradiol, Norethisterone, Cardiovascular risk, Diabetes, Menopause