Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein

Abstract

Objective: To examine the independent effects on insulin sensitivity and antioxidative activity of the three most prevalent constituents in Premarin (Wyeth-Ayerst Laboratories, Philadelphia, PA): estrone sulfate (E1S), 50%; equilin sulfate (EqS), 25%, and 17 alpha-dihydroequilin sulfate (17 alpha-ES), 15%.

Design: Prospective randomized cross-over study.

Setting: University of Southern California Medical Center.

Patient(s): Eight healthy postmenopausal women, mean age 53 +/- 2 years, and mean body mass index, 26 +/- 2 kg/m2, were enrolled.

Intervention(s): Each woman received, in randomized succession, daily oral doses of 17 alpha-ES (0.2 mg), E1S (0.625 mg), and EqS (0.3 mg) for 30 days.

Main outcome measure(s): Oxidation of low-density lipoprotein (LDL) by negatively charged LDL (LDL-) and lag phase duration and measured the plasma glucose disappearance after insulin administration (K(itt)).

Result(s): All three estrogen preparations demonstrated antioxidant effects with E1S demonstrating the most significant changes, followed by EqS and 17 alpha-ES. Using E1S, LDL-levels decreased from a baseline of 3.91 +/- 0.9 to 2.05 +/- 0.32 mg/dL and the lag time increased from 24.5 +/- 6.0 to 87.8 +/- 11.8 minutes. Changes in insulin tolerance tests revealed improved insulin action with the various estrogens. With EqS, K(itt) increased from 3.1% +/- 0.3% to 4.3% +/- 0.3% glucose/min, was intermediate with E1S and was least with 17 alpha-ES.

Conclusion(s): All three conjugated equine estrogens demonstrated antioxidant activity. Also, some improved insulin action was demonstrated. To our knowledge, this is the first in vivo study to examine the effects of these components which may help explain, in part, some of the cardioprotective properties ascribed to Premarin.