, 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


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.


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


Apo A–I

Apoliprotein A–I


Conjugated equine estrogen




Estrogen metabolites


Estrogen receptor


High density lipoprotein cholesterol


Hepatic lipase




Hormone replacement therapy


Liquid chromatography–tandem mass spectrometry


Low density lipoprotein cholesterol


Natural log




Myocardial infarction


Scavenger receptor class B type I


Women’s Health Initiative



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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