Insulin resistance with hormone replacement therapy: associations with markers of inflammation and adiposity

Abstract

This study was undertaken to determine whether insulin resistance associated with combination hormone replacement therapy (HRT) is mediated by changes in serum markers of inflammation or in serum adipocyte hormones. Forty-five postmenopausal women, aged 55 +/- 7 years, were examined from a randomized, double-blind placebo-controlled trial evaluating the effect of HRT on insulin-stimulated glucose disposal and body composition. Volunteers were randomly assigned to conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg vs placebo for 1 year. At baseline and at 1 year, body composition was assessed by dual photon x-ray absorptiometry scans; body fat distribution was measured by computed tomographic scans at the L4/L5 vertebral disk space; insulin sensitivity was measured by euglycemic hyperinsulinemic clamp; interleukin-6 (IL-6), leptin, and adiponectin were measured by enzyme-linked immunosorbent assay; and c-reactive protein (CRP) was measured by radioimmunoassay. HRT increased CRP by 121% compared with a 32% increase with placebo (P = .03); HRT decreased glucose disposal by 17% compared with no change with placebo (P = .04) as reported previously. HRT did not affect body composition, body fat distribution, IL-6, leptin, or adiponectin. The increase in CRP did not correlate with the decrease in glucose disposal in the HRT group (R = 0.11, P = .65). Treatment with HRT for one year increases CRP, but does not alter IL-6, adiponectin, or leptin. The change in CRP was not, however, related to the decrease in glucose disposal with HRT treatment.