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      Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to Insulin Action

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          Abstract

          Context:

          Type 2 diabetes (T2D) is reduced in postmenopausal women randomized to estrogen-based hormone therapy (HT) compared with placebo. Insulin sensitivity is a key determinant of T2D risk and overall cardiometabolic health, and studies indicate that estradiol (E 2) directly impacts insulin action.

          Objective:

          We hypothesized that the timing of E 2 administration after menopause is an important determinant of its effect on insulin action.

          Design:

          We performed a randomized, crossover, placebo-controlled study.

          Participants:

          Study participants were early postmenopausal (EPM; ≤6 years of final menses; n = 22) and late postmenopausal (LPM; ≥10 years since last menses; n = 24) women naive to HT.

          Intervention:

          Study interventions included short-term (1 week) transdermal E 2 and placebo.

          Main Outcomes and Measures:

          The study's main outcome was insulin-mediated glucose disposal (glucose disposal rate [GDR]) via hyperinsulinemic-euglycemic clamp.

          Results:

          Compared to EPM women, LPM women were older (mean ± SD; 63 ± 3 vs 56 ± 4 years, P < .05) and more years past menopause (12 ± 2 vs 3 ± 2 years, P < .05). Body mass index (24 ± 3 vs 25 ± 7 kg/m 2) and fat mass (25 ± 7 vs 23 ± 6 kg) did not differ between groups, but fat-free mass (FFM) was lower in LPM women compared to EPM women (40 ± 4 vs 43 ± 5 kg, P < .05). Baseline GDR did not differ between groups (11.7 ± 2.8 vs 11.5 ± 2.9 mg/kg FFM/min). In support of our hypothesis, 1 week of E 2 decreased GDR in LPM women compared to an increase in EPM women (+0.44 ± 1.7 vs − 0.76 ± 2.1 mg/kg FFM/min, P < .05).

          Conclusions:

          There was not an apparent decline in GDR with age or time since menopause per se. However, E 2 action on GDR was dependent on time since menopause, such that there was an apparent benefit early (≤6 years) compared to harm later (≥10 years) in menopause. E 2-mediated effects on insulin action may be one mechanism by which HT reduces the incidence of T2D in early postmenopausal women.

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          Author and article information

          Journal
          J Clin Endocrinol Metab
          J. Clin. Endocrinol. Metab
          jcem
          jceme
          jcem
          The Journal of Clinical Endocrinology and Metabolism
          Endocrine Society (Washington, DC )
          0021-972X
          1945-7197
          December 2015
          1 October 2015
          1 December 2016
          : 100
          : 12
          : 4456-4462
          Affiliations
          Department of Medicine (T.A.S., C.B.E., R.E.V.P.), Division of Geriatric Medicine; Department of Medicine (R.I.P., B.A.C.), Division of Endocrinology, Metabolism and Diabetes; Colorado School of Public Health, Biostatistics and Informatics (P.W.), University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045
          Author notes
          Address all correspondence and requests for reprints to: Rachael E. Van Pelt, Ph.D., Division of Geriatric Medicine, University of Colorado Anschutz Medical Campus, 12631 East 17th Ave, Campus Box B-179, Aurora, CO 80045. E-mail: rachael.vanpelt@ 123456ucdenver.edu .
          Article
          PMC4667161 PMC4667161 4667161 15-3084
          10.1210/jc.2015-3084
          4667161
          26425886
          054f85fd-e1e5-4ae4-8f7e-2b4062505e47
          Copyright © 2015 by the Endocrine Society
          History
          : 3 August 2015
          : 28 September 2015
          Categories
          6
          Original Articles

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