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


METHODS
Prospective randomized cross-over study.


METHODS
University of Southern California Medical Center.


METHODS
Eight healthy postmenopausal women, mean age 53 +/- 2 years, and mean body mass index, 26 +/- 2 kg/m2, were enrolled.


METHODS
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.


METHODS
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)).


RESULTS
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.


CONCLUSIONS
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.
Wilcox
J G
JG
University of Southern California School of Medicine, Los Angeles, California, USA.
Hwang
J
J
Hodis
H N
HN
Sevanian
A
A
Stanczyk
F Z
FZ
Lobo
R A
RA
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D003327:Coronary Disease / Q000517:prevention & control*; D018592:Cross-Over Studies; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D011446:Prospective Studies
D000975:Antioxidants; D001786:Blood Glucose; D004966:Estrogens, Conjugated (USP); D008077:Lipoproteins, LDL