Endogenous estradiol and inflammation biomarkers: potential interacting mechanisms of obesity-related disease.

Authors

Eldridge RC, Wentzensen N, Pfeiffer RM, Brinton LA, Hartge P, Guillemette C, Kemp TJ, Pinto LA, Trabert B

Affiliations

• Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. ronald.eldridge@emory.edu.
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
• Pharmacogenetics Laboratory, Faculty of Pharmacy, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Laval University, Quebec City, QC, Canada.
• HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc, Frederick, MD, USA.

Abstract

PURPOSE: Disentangling the effects of endogenous estrogens and inflammation on obesity-related diseases requires a clearer understanding of how the two biological mechanisms relate to each other.

METHODS: We studied 155 healthy postmenopausal women not taking menopausal hormone therapy enrolled in the Prostate Lung Colorectal and Ovarian (PLCO) screening cancer trial. From a baseline blood draw, we measured endogenous estradiol and 69 inflammation biomarkers: cytokines, chemokines, adipokines, angiogenic factors, growth factors, acute phase proteins, and soluble receptors. We evaluated the estradiol-inflammation relationship by assessing associations across different models (linear, ordinal logistic, and binary logistic) using a variety of estradiol classifications. We additionally investigated the estradiol-inflammation relationship stratified by baseline obesity status (BMI < 30 stratum and BMI > 30 stratum).

RESULTS: Associations of estradiol with 7 inflammation biomarkers met p < 0.05 statistical significance in linear and ordinal models: C-reactive protein (CRP), adiponectin, chemokine (C-X-C motif) ligand-6, thymus activation-regulated chemokine, eosinophil chemotactic protein, plasminogen activator inhibitor-1, and serum amyloid A. The positive association between estradiol and CRP was robust to model changes. Each standard deviation increase in endogenous estradiol doubled a woman's odds of having CRP levels higher than the study median (odds ratio 2.29; 95% confidence interval 1.28, 4.09). Estradiol was consistently inversely associated with adiponectin. Other estradiol-inflammation biomarker associations were not robust to model changes.

CONCLUSIONS: Endogenous estradiol appears to be associated with CRP and adiponectin; the evidence is limited for other inflammation biomarkers.