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Effects of metformin and leuprolide acetate on insulin resistance and testosterone levels in nondiabetic postmenopausal women: a randomized, placebo-controlled trial.

Author(s): Patel SM, Iqbal N, Kaul S, Ratcliffe SJ, Rickels MR, Reilly MP, Scattergood T, Basu A, Fuller C, Cappola AR

Affiliation(s): Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

Publication date & source: 2010-03-11, Fertil Steril., [Epub ahead of print]

OBJECTIVE: To determine whether insulin sensitizers lower androgen levels and whether androgen suppression improves insulin resistance in nondiabetic postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Clinical and Translational Research Center of a university hospital. PATIENT(S): Thirty-five postmenopausal women aged 50-79 years with insulin resistance and higher T levels. INTERVENTION(S): Subjects were randomized to metformin plus leuprolide acetate (LA) placebo, LA plus metformin placebo, or LA placebo plus metformin placebo in a 1:1:1 fashion during a 12-week period. MAIN OUTCOME MEASURE(S): Insulin sensitivity (M) assessed by euglycemic-hyperinsulinemic clamp and free T by equilibrium dialysis. RESULT(S): In those randomized to metformin, free T decreased by 19% compared with placebo, along with an expected improvement in M. Total T also decreased significantly, whereas sex hormone-binding globulin (SHBG) did not change. In those randomized to LA, the percent change in M was not different from placebo, despite a 48% relative decrease in free T levels. CONCLUSION(S): These data are the first to establish a causal link between insulin resistance and T in postmenopausal women. They confirm that treatment of insulin resistance decreases T production in this population and demonstrate that pharmacologic lowering of T does not affect insulin resistance. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Page last updated: 2010-10-05

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