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 menop-ause. 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.
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