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

Abstract

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.

Figure 1

Secondary analysis design. We conducted an analysis of the effectiveness of glucose-lowering interventions in a randomized trial (the Diabetes Prevention Program), among postmenopausal women who were either 1) oral estrogen users at baseline and at 1-year follow-up or 2) non-estrogen users at baseline and at 1-year follow-up.

Figure 2

Changes in fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2HG) between baseline and year 1 follow-up, among estrogen therapy (ET) users and non-users. Means and 95% confidence intervals shown; * indicate significant differences from placebo arm.

Figure 3

Changes in select sex hormone measures (sex hormone binding globulin or SHBG, bioavailable estradiol or bioE2, total estradiol or total E2) between baseline and year 1 follow-up, among estrogen therapy (ET) users and non-users. Means and 95% confidence intervals shown; * indicate significant differences from placebo arm.