Androgen activity as a risk factor for impaired glucose tolerance in postmenopausal women

OBJECTIVE - Low sex hormone-binding globulin (SHBG) has been proposed as a risk factor for NIDDM development in women. Our aim was to study the relationship between SHBG and androgen activity and glucose tolerance, as well as insulin sensitivity, in women with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS - We studied 22 women with IGT and 46 women with normal glucose tolerance (NGT) aged 57-59 years. Free testosterone (androgen activity) was determined as the testosterone-to-SHBG ratio. A World Health Organization 75 g oral glucose tolerance test (OGTT) was performed, and insulin sensitivity was measured with a euglycemic-hyperinsulinemic clamp. RESULTS - Fasting glucose (P = 0.021), 2-h blood glucose after the OGTT (P < 0.001), and fasting insulin (P = 0.009) were higher in the IGT group, while insulin sensitivity did not differ significantly between the two groups (P = 0.065). We found that SHBG levels were lower in the IGT group (P = 0.004), while the testosterone-to-SHBG ratio was higher in the IGT than in the NGT group (P = 0.004). Insulin sensitivity correlated negatively with testosterone-to-SHBG ratio in both groups. The correlation was higher in the IGT (r = -0.67, P = 0.001) than in the NGT group (r = -0.29, P = 0.047). In contrast, the 2-h blood glucose correlated with testesterone-to-SHBG ratio in the IGT (r = 0.66, P = 0.001) but not the NGT group (r = -0.04, NS). CONCLUSIONS - Postmenopausal women with IGT have higher androgen activity than women with NGT, and the androgen activity correlates with the degree of glucose intolerance in IGT. Furthermore, in women with IGT, who have a high risk of NIDDM development, androgen activity seems to have an enhanced negative influence on insulin sensitivity. Therefore, androgen activity appears to be a risk factor for IGT.