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

Abstract

Objective-To determine if insulin resistance associated with combination hormone replacement therapy (HRT) is mediated by changes in serum markers of inflammation or in serum adipocyte hormones.Study design-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 randomized 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 (DEXA); body fat distribution was measured by CT scans at the L4/L5 vertebral disc space; insulin sensitivity was measured by euglycemic hyperinsulinemic clamp; interleukin-6 (IL-6), leptin and adiponectin were measured by ELISA; and c-reactive protein (CRP) was measured by RIA.Results-HRT increased CRP by 121% compared to a 32% increase with placebo (p=0.03); HRT decreased glucose disposal by 17% compared to no change with placebo (p=0.04) 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=0.65).Conclusion-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.

Estrogen replacement therapy decreases plasma adiponectin but not resistin in postmenopausal women

“…In the present study, neither treatment affected the BMI (Table 1). In other studies, PE treatment has been combined with progesterone, resulting in either no change [20,27] or decrease [28] in plasma adiponectin concentrations; but the use of progesterone prevents a reliable comparison with our results.…”

Effect of Hormones on Matrix Metalloproteinases Gene Regulation in Human Aortic Smooth Muscle Cells

“…The expression of estrogen-binding receptors in the microenvironment has been positively correlated to levels of inflammatory cytokines IL-1␤, TNF-␣, and IL-6 [26]. Furthermore, estrogen has been found to induce pro-inflammatory cytokines IL-1␤, TNF-␣, and C-reactive protein and to generate reactive oxygen species and nitrogen species [27,28]. In contrast, estrogen in combination with progesterone has been found to decrease IL-1␤-stimulated vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 [29], important in inflammatory reactions.…”

Insulin-sensitive obesity

“…It has been demonstrated that hormone replacement therapy decreases insulin sensitivity (9). Moreover, it has been argued that insulin-sensitive obesity is mainly a phenotype seen in premenopausal women, who become insulin resistant after menopause.…”