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Reductions in glucose among postmenopausal women who use and do not use estrogen therapy

Kim, Catherine MD, MPH1; Kong, Shengchun MS1; Laughlin, Gail A. PhD2; Golden, Sherita H. MD, MHS3; Mather, Kieren J. MD4; Nan, Bin PhD1; Randolph, John F. Jr MD1; Edelstein, Sharon L. ScM5; Labrie, Fernand MD, PhD6,7; Buschur, Elizabeth MD1; Barrett-Connor, Elizabeth MD2for The Diabetes Prevention Program Research Group

doi: 10.1097/gme.0b013e3182703b73
Original Articles

Objective Among postmenopausal women who do not use estrogen therapy (ET), we have previously reported that intensive lifestyle modification (ILS) leads to increases in sex hormone–binding globulin (SHBG) and that such increases are associated with reductions in fasting plasma glucose (FPG) and 2-hour postchallenge glucose (2HG). Oral ET decreases FPG and increases 2HG while increasing both SHBG and estradiol (E2). It is unknown if ILS reduces glucose among ET users, if changes in SHBG and E2 might mediate any glucose decreases in ET users, and if these patterns differ from those in non-ET users.

Methods We conducted a secondary analysis of postmenopausal women in the Diabetes Prevention Program who used ET at baseline and 1-year follow-up (n = 324) and who did not use ET at either time point (n = 382). Participants were randomized to ILS, metformin, or placebo administered at 850 mg BID.

Results ET users were younger, more often white, and more likely to have had bilateral oophorectomy than non-ET users. Among ET users, ILS reduced FPG (P < 0.01) and 2HG (P < 0.01), and metformin reduced FPG (P < 0.01) but not 2HG (P = 0.56), compared with placebo. Associations between SHBG and total E2 with FPG and 2HG were not significant among women randomized to ILS or metformin. These patterns differed from those observed among women who did not use ET.

Conclusions We conclude that among glucose-intolerant ET users, interventions to reduce glucose are effective but possibly mediated through different pathways than among women who do not use ET.

From the 1University of Michigan, Ann Arbor, MI; 2University of California, San Diego, CA; 3Johns Hopkins University, Baltimore, MD; 4Indiana University, Indianapolis, IN; 5George Washington University, Rockville, MD; 6Laval University, Quebec City, Canada; and 7Al Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia.

Received June 10, 2012; revised and accepted August 16, 2012.

These results were presented in abstract form at the 2012 American Diabetes Association Scientific Sessions in Philadelphia, PA.

The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies.

Funding/support: This work was supported by National Institutes of Health grants U01DK048489, R01DK083297, and K23DK071552. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the coordinating center for the design and conduct of the study, as well as for data collection, management, analysis, and interpretation of the Diabetes Prevention Program. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program of the National Center for Research Resources supported data collection in many of the clinical centers. Funding for data collection and participant support were also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the Office of Research on Women’s Health, the Office of Research on Minority Health, the Centers for Disease Control and Prevention, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc., Health O Meter, Hoechst Marion Roussel Inc., Merck-Medco Managed Care Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center.

Financial disclosure/conflicts of interest: None declared.

Address correspondence to: Catherine Kim, MD, MPH, Room 7C13, 300 North Ingalls Building, Mailstop 5429, Ann Arbor, MI 48109-5429. E-mail:

© 2013 by The North American Menopause Society.