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Serum 2-Methoxyestradiol, an Estrogen Metabolite, is Positively Associated with Serum HDL-C in a Population-Based Sample

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Lipids

Abstract

Serum HDL cholesterol (HDL-C) is inversely associated with coronary artery disease, ischemic stroke, and atherosclerosis in men and women. Among postmenopausal women, oral conjugated equine estrogen (CEE) increases serum HDL-C. This is due to activation of hepatic nuclear estrogen receptors, resulting in increased HDL-C expression, as well as modulation of proteins which metabolize HDL-C. 2-methoxyestradiol (2-MeOE2), an estrogen metabolite, has several vasculoprotective effects and may play a role in HDL-C production. 2-MeOE2 inhibits HMG-CoA reductase in vitro but no study has examined the relationship between serum 2-MeOE2 and serum HDL-C. A population-based sample provided information regarding demographic characteristics and use of antihyperlipidemic medications. Serum was analyzed for 17β-estradiol (E2), estrogen metabolites (EMs), and lipoproteins. Results included serum EM data from 51 men and 47 postmenopausal women. Preliminary analysis revealed no correlation between 2-MeOE2 and serum HDL-C in men so the current analysis includes only women (N = 40) with no missing demographic, medication, EM, or lipoprotein data. Linear regression revealed that serum 2-MeOE2 and antihyperlipidemic medications were positively associated with serum HDL-C (β = 0.276, P = 0.043, and β = 0.307, P = 0.047, respectively) when age, race/ethnicity, and body mass index were held constant. Prospective studies are needed to determine if 2-MeOE2 is causally related to HDL-C in women.

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Abbreviations

Apo A–I:

Apoliprotein A–I

CEE:

Conjugated equine estrogen

E2:

17β-Estradiol

EM:

Estrogen metabolites

ER:

Estrogen receptor

HDL-C:

High density lipoprotein cholesterol

HL:

Hepatic lipase

HMG-CoA:

3-Hydroxy-3methylglutaryl-CoA

HRT:

Hormone replacement therapy

LC–MS/MS:

Liquid chromatography–tandem mass spectrometry

LDL-C:

Low density lipoprotein cholesterol

ln:

Natural log

2-MeOE2:

2-Methoxyestradiol

MI:

Myocardial infarction

SR-BI:

Scavenger receptor class B type I

WHI:

Women’s Health Initiative

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Acknowledgments

This work was supported by a National Institute on Aging Career Development K08 Award (AG027200, C.M. Masi, PI), a National Institute on Aging R01 Award (AG036433, L.C. Hawkley, PI), and a National Institute on Aging R01 Award (AG034052, J.T. Cacioppo, PI).

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Authors and Affiliations

  1. Section of General Internal Medicine, University of Chicago, 5841 S. Maryland Avenue, M/C 2007, Chicago, IL, USA

    Christopher M. Masi

  2. Department of Psychology, University of Chicago, Chicago, IL, USA

    Louise C. Hawkley & John T. Cacioppo

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  1. Christopher M. Masi
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  2. Louise C. Hawkley
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  3. John T. Cacioppo
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Correspondence to Christopher M. Masi.

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Masi, C.M., Hawkley, L.C. & Cacioppo, J.T. Serum 2-Methoxyestradiol, an Estrogen Metabolite, is Positively Associated with Serum HDL-C in a Population-Based Sample. Lipids 47, 35–38 (2012). https://doi.org/10.1007/s11745-011-3600-y

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  • DOI: https://doi.org/10.1007/s11745-011-3600-y

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