Endogenous Sex Hormone Changes in Postmenopausal Women in the Diabetes Prevention Program

Context: Whether endogenous sex hormones (ESH) [SHBG, estradiol, testosterone, and dehydroepiandrosterone (DHEA)] are altered by intensive lifestyle modification (ILS) or metformin and whether such changes affect glucose levels among dysglycemic postmenopausal women is unclear. Objectives: Our objective was to examine intervention impact on ESH and associations with fasting plasma glucose (FPG) and 2-h glucose changes among postmenopausal glucose-intolerant women. Design: We performed a secondary analysis of a randomized controlled trial. Participants: Participants included postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n = 382) who participated in the Diabetes Prevention Program. Interventions: Interventions included ILS with the goals of weight reduction of at least 7% of initial weight and 150 min/wk of moderate intensity exercise or metformin or placebo administered 850 mg twice a day. Main Outcome Measures: Intervention-related changes in ESH and associations of changes in ESH and glucose levels were evaluated. Results: ILS significantly increased SHBG and decreased DHEA before and after adjustment for changes in waist circumference and fasting insulin. ILS did not alter estradiol or testosterone. Metformin did not change any ESH. ILS-induced increases in SHBG and declines in DHEA were associated with decreases in FPG and 2-h glucose, and declines in estradiol were associated with decreases in FPG, before and after adjustment for age, FSH, race/ethnicity, changes in waist circumference, and 1/fasting insulin. Conclusions: Among postmenopausal glucose-intolerant women not using estrogen, ILS increased SHBG levels and lowered DHEA levels. These changes were associated with lower glucose independent of adiposity and insulin. Metformin effects upon ESH were not significant. (J Clin Endocrinol Metab 97: 2853-2861, 2012)