Effect of conjugated estrogens and bazedoxifene on glucose, energy and lipid metabolism in obese postmenopausal women

in European Journal of Endocrinology
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  • 1 Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
  • 2 Tulane University Health Sciences Center, New Orleans, Louisiana, USA
  • 3 Southeast Louisiana Veterans Administration Healthcare System, New Orleans, Louisiana, USA
  • 4 Baton Rouge General Hospital, Baton Rouge, Louisiana, USA
  • 5 Departments of Internal Medicine, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA

Correspondence should be addressed to F Mauvais-Jarvis; Email: fmauvais@tulane.edu

*(K L Marlatt and D Lovre contributed equally to this work)

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Objective:

Combining conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is a novel, orally administered menopausal therapy. We investigated the effect of CE/BZA on insulin sensitivity, energy metabolism, and serum metabolome in postmenopausal women with obesity.

Design:

Randomized, double-blind, crossover pilot trial with washout was conducted at Pennington Biomedical Research Center. Eight postmenopausal women (age 50–60 years, BMI 30–40 kg/m2) were randomized to 8 weeks CE/BZA or placebo. Primary outcome was insulin sensitivity (hyperinsulinemic-euglycemic clamp). Secondary outcomes included body composition (DXA); resting metabolic rate (RMR); substrate oxidation (indirect calorimetry); ectopic lipids (1H-MRS); fat cell size, adipose and skeletal muscle gene expression (biopsies); serum inflammatory markers; and serum metabolome (LC/MS).

Results:

CE/BZA treatment produced no detectable effect on insulin sensitivity, body composition, ectopic fat, fat cell size, or substrate oxidation, but resulted in a non-significant increase in RMR (basal: P = 0.06; high-dose clamp: P = 0.08) compared to placebo. CE/BZA increased serum high-density lipoprotein (HDL)-cholesterol. CE/BZA also increased serum diacylglycerol (DAG) and triacylglycerol (TAG) species containing long-chain saturated, mono- and polyunsaturated fatty acids (FAs) and decreased long-chain acylcarnitines, possibly reflecting increased hepatic de novo FA synthesis and esterification into TAGs for export into very low-density lipoproteins, as well as decreased FA oxidation, respectively (P < 0.05). CE/BZA increased serum phosphatidylcholines, phosphatidylethanolamines, ceramides, and sphingomyelins, possibly reflecting the increase in serum lipoproteins (P < 0.05).

Conclusions:

A short treatment of obese postmenopausal women with CE/BZA does not alter insulin action or ectopic fat but increases serum markers of hepatic de novo lipogenesis and TAG production.

Supplementary Materials

    • Supplemental Table 1. Effect of CE/BZA on Serum Global Metabolomics Panel
    • Supplemental Table 2. Effect of CE/BZA on Serum Complex Lipidomics Panel
    • Supplemental Table 3. Effect of CE/BZA on Muscle Global Metabolomics Panel

 

     European Society of Endocrinology

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