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Apr 29, 2009

Hormone Replacement Therapy’s Effects on the Proteome Revealed

  • Scientists from the Fred Hutchinson Cancer Research Center have uncovered changes that take place in the serum proteome related to hormone replacement therapy. They report finding that estrogen upregulates proteins involved in several major body processes.

    “As many as 10 percent of plasma proteins analyzed were found to be affected by estrogen hormone replacement therapy in post-menopausal women,” notes Samir Hanash, M.D., Ph.D. “These changes indicate a substantial effect on coagulation and metabolic proteins that may explain the increased risk of venous thromboembolism and stroke and the reduced risk of fracture found in the WHI (Women’s Health Initiative) trial.”

    The authors used baseline and one-year post-treatment sera samples from 50 women in the WHI trial separated into five experimental pools. The average age of the subjects was 61.4 years. There were no statistically significant differences in any baseline characteristics between pools. A subset of proteins that exhibited increased levels with estrogen therapy by quantitative proteomics was selected for validation studies.

    Of 611 proteins quantified based on differential stable isotope labeling, the levels of 116 (19%) were changed after one year of treatment, while 64 of these had estimated false discovery rates. Most of the changed proteins were not previously known to be affected by hormone replacement therapy and had relevance to processes that included coagulation, metabolism, osteogenesis, inflammation, and blood pressure maintenance.

    To validate quantitative proteomic data, 14 proteins were selected for ELISA. Findings for 10 (IGF1, IGFBP4, IGFBP1, IGFBP2, F10, AHSG, GC, CP, MMP2, and PROZ) were confirmed in the initial set of 50 subjects and further validated in an independent set of 50 additional subjects who received hormone replacement therapy.

    The findings appear in Genome Medicine in a study called “Application of serum proteomics to the Women's Health Initiative conjugated equine estrogens trial reveals a multitude of effects relevant to clinical findings.”



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