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Endogenous Sex Hormones and Glucose Tolerance Status in Postmenopausal Women

Departments of Medicine (S.H.G., A.S.D., D.V., P.O.) and Epidemiology (S.H.G., M.S.), Johns Hopkins University, Baltimore, Maryland 21205; and Divisions of Endocrinology, Metabolism and Molecular Medicine (P.K.) and Department of Preventive Medicine (S.G., K.L.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611

Address all correspondence and requests for reprints to: Sherita Hill Golden, M.D., M.H.S., Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 2024 East Monument Street, Suite 2-600, Baltimore, Maryland 21205. E-mail: sahill{at}jhmi.edu.

Context: In postmenopausal women, endogenous estradiol (E2) and free testosterone (T) have been positively associated with glucose intolerance and type 2 diabetes. Most studies have not examined these associations in a large group of postmenopausal women.

Objective: The objective was to examine the association between endogenous sex hormones and glucose tolerance in postmenopausal women.

Design, Setting, and Participants: This was a cross-sectional study of 1973 postmenopausal women ages 45–84 yr, not taking hormone replacement therapy, in the Multi-Ethnic Study of Atherosclerosis baseline examination.

Main Outcome Measures: Impaired fasting glucose (IFG) and diabetes were defined based on fasting blood sugar and/or treatment for diabetes. In women with normal glucose tolerance, insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR).

Results: Increasing quartiles of bioavailable T and E2 and decreasing quartiles of SHBG were associated with significantly increased odds of IFG and diabetes (all P for trend < 0.001). Except for the association of bioavailable T with diabetes, the other associations persisted after multivariable adjustment. Although higher dehydroepiandrostenedione (DHEA) was associated with greater odds of IFG (P for trend = 0.02), it was not associated with diabetes. Of 1100 women with normal glucose tolerance, E2 and DHEA were positively associated, and SHBG was inversely associated with HOMA-IR (all P < 0.001) after multivariable adjustment. Bioavailable T was associated with HOMA-IR (P < 0.001), but not fasting glucose.

Conclusion: Of postmenopausal women, endogenous bioavailable T, E2, and DHEA were positively associated and SHBG was negatively associated with insulin resistance.