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CLINICAL STUDY: ATHEROSCLEROSIS

Estrogen-induced small low density lipoprotein particles may be atherogenic in postmenopausal women

^a Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan

Manuscript received June 7, 2000; revised manuscript received September 8, 2000, accepted October 26, 2000.

Reprint requests and correspondence: Dr. Akihiko Wakatsuki, Department of Obstetrics and Gynecology, Kochi Medical School, Oko cho, Nankoku, Kochi, Japan 783-8505
wakatuki{at}kochi-ms.ac.jp

OBJECTIVES

The purpose of this study was to investigate the susceptibility of estrogen-induced small low density lipoprotein (LDL) particles to oxidation.

BACKGROUND

Estrogen replacement therapy in postmenopausal women has an antioxidant effect that opposes oxidation of LDL particles. Estrogen-induced increases in plasma triglyceride concentrations, however, decrease LDL particle size, which may act counter to this antioxidant effect. It has not been evaluated whether estrogen-induced small LDL particles are atherogenic.

METHODS

In 24 lean and healthy postmenopausal women treated with conjugated equine estrogen (0.625 mg daily) for three months, plasma lipid concentrations and diameter of LDL particles were measured before and after therapy. Susceptibility of LDL to oxidation was determined by measuring the concentration of thiobarbituric acid-reactive substances (TBARS) after incubation with CuSO₄.

RESULTS

Estrogen significantly decreased plasma concentrations of total cholesterol, LDL-cholesterol and apolipoprotein B, while increasing concentrations of triglyceride, high-density lipoprotein cholesterol and apolipoprotein A-I. Estrogen-induced changes in LDL particle diameter correlated negatively with changes in plasma triglyceride concentrations (r = –0.55, p < 0.005) and with changes in concentrations of LDL-derived TBARS (r = –0.49, p < 0.005). In subjects with substantial estrogen-induced plasma triglyceride increases, estrogen significantly reduced the diameter of LDL particles (p < 0.05) and significantly increased the concentration of LDL-derived TBARS (p < 0.05). In contrast, estrogen significantly reduced the concentration of LDL-derived TBARS (p < 0.05) and caused no significant change in LDL particle diameter in subjects whose plasma triglyceride concentration was unchanged with estrogen therapy.

CONCLUSIONS

Because estrogen-induced plasma triglyceride increases may produce small LDL particles that are more susceptible to oxidation, antioxidant effects of estrogen might be offset in patients showing such a triglyceride increase.

Abbreviations and Acronyms   CHD = coronary heart disease   EDTA = ethylenediaminetetra-acetic acid   ERT = estrogen replacement therapy   E1 = estrone   E2 = estradiol   HDL = high density lipoprotein   HERS = Heart and Estrogen/progestin Replacement Study   LDL = low density lipoprotein   TBARS = thiobarbituric acid-reactive substances

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