title: Serum 2-methoxyestradiol, an estrogen metabolite, is positively associated with serum HDL-C in a population-based sample.
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.
authors.affiliation: Section of General Internal Medicine, University of Chicago, 5841 S. Maryland Avenue, M/C 2007, Chicago, IL, USA, cmasi@medicine.bsd.uchicago.edu.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Masi
authors.forename: Louise C
authors.initials: LC
authors.lastname: Hawkley
authors.forename: John T
authors.initials: JT
authors.lastname: Cacioppo
mesh_terms: D000077584:2-Methoxyestradiol; D000214:Acyl Coenzyme A / Q000097:blood*; D001741:Black or African American; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood*; D002853:Chromatography, Liquid; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D008074:Lipoproteins / Q000097:blood; D013058:Mass Spectrometry; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood* / Q000187:drug effects / Q000208:ethnology; D014280:Triglycerides / Q000097:blood; D014481:United States / Q000453:epidemiology; D044465:White People
chemical_list: D000214:Acyl Coenzyme A; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D004958:Estradiol; D000077584:2-Methoxyestradiol