MON-158 - Proteomics Profiling of Obese Postmenopausal Women Treated with Conjugated estrogens and Bazedoxifene.

Background:
Obesity in postmenopausal women is associated with insulin resistance, dyslipidemia, and low-grade systemic inflammation. Conjugated estrogens / bazedoxifene (CE/BZA) produce metabolic benefits in this population, but the underlying molecular mechanisms remain unclear. We applied a multi-omics approach to define pathway signatures associated with CE/BZA treatment.

Methods:
Stored plasma samples from a previously published 12-week randomized, placebo-controlled trial of CE/BZA versus placebo in obese postmenopausal women (CE/BZA n=7, placebo n=5) underwent untargeted proteomic, lipidomic and metabolomic profiling at baseline and week 12. Here we report proteomic findings using bioinformatic analysis performed using custom R-scripts Ingenuity Pathway Analysis (QIAGEN).

Results:
CE/BZA induced marked proteomic alteration characterized by increased activation of leukocytes, antigen-presenting cells, phagocytes, granulocytes, and neutrophils, along with enhanced cell movement and chemotaxis compared to placebo. Despite enrichment of immune activation, pathway analysis indicated that CE/BZA reduced accumulation of phagocytes, granulocytes, and neutrophils, consistent with increased immune activation but reduced chronic inflammation compared to placebo. CE/BZA treatment arm was further associated with reduced inflammatory signaling in liver, respiratory, and intestinal systems compared to placebo. Notably, the CE/BZA treatment arm exhibited decreased pathways of breast and gynecologic cancers compared to placebo.

Conclusion:
These findings identify new mechanistic insight into the pleiotropic effects of CE/BZA in menopausal women.

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