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Lipids

, Volume 47, Issue 1, pp 35–38 | Cite as

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

  • Christopher M. MasiEmail author
  • Louise C. Hawkley
  • John T. Cacioppo
Communication

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.

Keywords

HDL Lipoprotein metabolism Mass spectrometry Atherosclerosis Coronary artery disease HMG-CoA reductase 

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

Notes

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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Copyright information

© AOCS 2011

Authors and Affiliations

  • Christopher M. Masi
    • 1
    Email author
  • Louise C. Hawkley
    • 2
  • John T. Cacioppo
    • 2
  1. 1.Section of General Internal MedicineUniversity of ChicagoChicagoUSA
  2. 2.Department of PsychologyUniversity of ChicagoChicagoUSA

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