Context: In post-menopausal 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 post-menopausal women.

Objective: Our objective was to examine the association between endogenous sex hormones and glucose tolerance in post-menopausal women.

Design, Setting, and Participants: This was a cross-sectional study of 1,973 post-menopausal women ages 45-84 years, 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 sex hormone binding globulin (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 following multivariable adjustment. While higher dehydroepiandrostenedione (DHEA) was associated with a greater odds of IFG (p for trend=0.02), it was not associated with diabetes. Among 1,100 women with normal glucose tolerance, E2 and DHEA were positively associated and SHBG was inversely associated with HOMA-IR (all p<0.001) following multivariable adjustment. Bioavailable T was associated with HOMA-IR (p<0.001) but not fasting glucose.

Conclusion: Among post-menopausal women, endogenous bioavailable T, E2, and DHEA were positively, and SHBG negatively associated with insulin resistance.