Higher Insulin Resistance And Adiposity In Postmenopausal Women With Breast Cancer Treated With Aromatase Inhibitors

Context: Aromatase deficiency causes obesity and insulin resistance in aromatase knockout mice and humans with rare mutations of the aromatase gene (CYP19). Aromatase inhibitors are a commonly prescribed therapy for postmenopausal breast cancer.Objective: We hypothesized that aromatase inhibitors induce obesity and insulin resistance when used in treatment of breast cancer.Design: Case-control study.Setting: University teaching hospital.Participants: Patients with postmenopausal breast cancer (n = 20) treated with aromatase inhibitors and 20 age-matched control subjects.Main outcome measures: The primary outcome measure was insulin sensitivity index - Matsuda, derived from a 75-g oral glucose tolerance test. Body composition was assessed by dual energy x-ray absorptiometry and biopsy specimens of subcutaneous adipose tissue obtained for assessment of mRNA transcript levels. Data are reported as mean +/- SEM (patients receiving inhibitors vs control group, respectively).Results: Aromatase inhibitor therapy was associated with significantly lower insulin sensitivity (5.15 +/- 0.45 vs 6.80 +/- 0.64; P = 0.041), higher peak insulin concentration after oral glucose tolerance test (693.4 +/- 78.6 vs 527.6 +/- 85.5 pmol/L; P = 0.035), greater percentage of body fat (38.4% +/- 1.0% vs 34.6% +/- 1.3%; P = 0.026), and higher plasma leptin concentration (23.5 +/- 2.8 vs 15.5 +/- 2.3 ng/mL; P = 0.035).Conclusion: Women who received aromatase inhibitors for postmenopausal breast cancer had greater percentage body fat and insulin resistance compared with control subjects with no history of breast cancer.