Serum metabolomic profiles associated with postmenopausal hormone use
Postmenopausal hormone use is linked to several health outcomes and the risk associated with some may differ depending on whether estrogen is used alone or in combination with progestin.
Metabolomic analyses of postmenopausal hormone use and differences between hormone regimes was done to identify metabolites associated with each type of hormone treatment.
Untargeted metabolomics analysis was done on serum from 1336 women enrolled in the Cancer Prevention II Nutrition Cohort. Levels of 781 named metabolites were compared between 667 nonusers with 332 estrogen-only and with 337 estrogen plus progestin users using linear regression. Metabolite levels were also compared between estrogen-only and estrogen plus progestin users.
Compared to nonusers, 276 metabolites were statistically significantly (P < 6.40 × 10− 5) associated with estrogen-only use and 222 were associated with estrogen plus progestin use. The metabolites associated with both types of hormones included numerous lipids, acyl carnitines, and amino acids as well as the thyroid hormone thyroxine and the oncometabolite fumarate. The 65 metabolites that differed significantly between estrogen-only and estrogen plus progestin users included 19 steroids and 12 lipids that contained the bioactive fatty acid arachidonic acid.
These findings suggest that postmenopausal hormone use influences metabolic pathways linked to a variety of cellular processes, including the regulation of metabolism and stress responses, energy production, and inflammation. The differential association of numerous lipids which influence cellular signaling suggests that differences in signal transduction may contribute to the disparate risks for some diseases between estrogen-only and estrogen plus progestin users.
KeywordsHormone replacement therapy Estrogen Progestin Postmenopausal
The authors express sincere appreciation to all Cancer Prevention Study II participants and to each member of the study and biospecimen management group. We also thank Dr. Steven Moore (National Cancer Institute) for assistance in obtaining partial financial support for this project.
The views expressed here are those of the authors and do not necessarily represent the American Cancer Society or the American Cancer Society—Cancer Action Network.
Conception and design: V.L. Stevens; Acquisition of the data: V.L. Stevens, Y. Wang, B.D. Carter; Analysis and interpretation of the data: V.L. Stevens, Y. Wang, B.D. Carter; Writing and review of the manuscript: V.L. Stevens, Y. Wang, M.M. Gaudet, S.M. Gapstur.
The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort. The metabolomic analyses were supported, in part, through the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest.
All aspects of the CPS-II Nutrition Cohort were approved by the Emory University Institutional Review Board (IRB00045780).
Informed consent was obtained from all individual participants included in this study.
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