Predictors of worsening insulin sensitivity in postmenopausal women.

OBJECTIVE: The purpose of this study was to determine predictors of worsening insulin sensitivity in postmenopausal women. STUDY DESIGN: Seventy-one nonobese postmenopausal women were assigned randomly to receive hormone replacement therapy (conjugated estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg) or placebo daily for 1 year (34 women received hormone replacement therapy, and 37 women received placebo). At baseline and 12 months, the women received a computed tomography scan at the L4-L5 vertebral disk space, a dual x-ray absorptiometry scan, a euglycemic hyperinsulinemic clamp to measure insulin sensitivity, and a lipid profile. Declining insulin sensitivity was defined as the largest quartile change in insulin sensitivity in the women who received the placebo (-1.42 mg/min/kg lean body mass). RESULTS: By univariate analysis, we found that significant predictors of worsening insulin sensitivity were the use of hormone replacement therapy, baseline insulin sensitivity, a younger age, and <10 years since menopause. By logistic regression, we determined that hormone replacement therapy use and higher baseline insulin sensitivity were independent predictors of worsening insulin sensitivity. CONCLUSION: The use of hormone replacement therapy and baseline insulin sensitivity are significant independent predictors of the development of worsening insulin sensitivity in postmenopausal women.

The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: a randomized, double-blind, placebo-controlled trial.

PURPOSE: After menopause, women gain abdominal fat and become less sensitive to insulin. We sought to determine whether hormone replacement therapy (HRT) reduced intraabdominal and sc abdominal fat and improved insulin sensitivity in early menopausal women. METHODS: Seventy-six postmenopausal women, age 51.6 +/- 3.9 yr with body mass index of 24.9 +/- 3.2 kg/m2, were randomized to conjugated estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) or placebo daily. Women received a computed tomography scan at the L4-L5 vertebral disk space, a dual x-ray absorptiometry scan, and a euglycemic hyperinsulinemic clamp at baseline, 6 months, 1 yr, and 2 yr. RESULTS: Fifty-one women completed the trial and were analyzed (n = 26 on HRT and n = 25 on placebo). Intraabdominal fat, sc abdominal fat, total fat, percent fat, fat-free mass, and weight did not differ between treatment groups by time. Insulin sensitivity did not change in the placebo group, but decreased by 17% in the HRT group by 6 months and persisted at 2 yr (P < 0.01 for treatment by time effect). One year after the trial, insulin sensitivity increased by 25% in women who had taken HRT (P = 0.006 for treatment by time effect), to a level similar to those women in the placebo group. CONCLUSIONS: Conjugated estrogens plus medroxyprogesterone acetate reduce insulin sensitivity in menopausal women without affecting body composition or body fat distribution. The reduction in insulin sensitivity is reversible after discontinuing HRT.

Menopause-related differences in inflammation markers and their relationship to body fat distribution and insulin-stimulated glucose disposal.

OBJECTIVE: To determine whether postmenopausal status is associated with elevated plasma inflammation markers compared to premenopausal status, and how this explains differences in fat distribution and insulin-stimulated glucose disposal. DESIGN: Cross-sectional. SETTING: Clinical research center. PATIENT(S): Forty-five premenopausal women and 44 postmenopausal women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured by ELISA. Intraabdominal, subcutaneous abdominal, and total fat were measured by computed tomographic scan and dual-photon x-ray absorptiometry. Insulin-stimulated glucose disposal was measured by euglycemic clamp. RESULT(S): The TNF-alpha was higher in postmenopausal compared to premenopausal women (4.81 +/- 1.99 vs. 3.54 +/- 0.85 pg/mL). Interleukin-6 and CRP did not differ by menopausal status. In both premenopausal and postmenopausal women, CRP was related positively to total fat. The CRP was related to intraabdominal fat only in postmenopausal women and was negatively related to insulin-stimulated glucose disposal in both premenopausal and postmenopausal women. CONCLUSION(S): Postmenopausal status is characterized by higher TNF-alpha. The CRP may be associated with increased cardiovascular risk in postmenopausal women by its association with higher intraabdominal fat. Higher CRP is associated with lower insulin-stimulated glucose disposal in both premenopausal and postmenopausal women.