Differential Effects of Raloxifene and Estrogen on Insulin Sensitivity in Postmenopausal Women

OBJECTIVES: To test the hypothesis that both raloxifene and estrogen would improve insulin sensitivity in postmenopausal women and that the magnitude of the effect would be similar for both drugs. DESIGN: Placebo‐controlled, double‐blind, randomized study. SETTING: The General Clinical Research Center of the University of Michigan Medical Center, a university hospital. PARTICIPANTS: Forty‐four healthy postmenopausal women 73 ± 7 years old (mean age ± standard deviation) who were not receiving hormone replacement therapy. INTERVENTION: Eight weeks of drug therapy with randomization to raloxifene (n = 16), estrogen (n = 14), or placebo (n = 14). MEASUREMENTS: These subjects underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (S I ) and total and regional (central) body composition measurements by dual‐energy x‐ray absorptiometry at baseline and after 8 weeks of drug therapy. RESULTS: There were no statistically significant differences in age, body mass index, total or central fat mass, or S I between the three groups at baseline. The major outcome variable was S I . After 8 weeks of drug therapy, there was no significant change in S I in the placebo group or in the estrogen group and a significant decrease in S I in the raloxifene group, P = .003. CONCLUSION: In contrast to estrogen's ability to maintain insulin sensitivity, raloxifene decreases insulin sensitivity in healthy nondiabetic postmenopausal women. The clinical significance of this effect of raloxifene to impair insulin sensitivity in postmenopausal women warrants further evaluation in future studies.