HYPERINSULINEMIA AND SEX-HORMONES IN HEALTHY PREMENOPAUSAL WOMEN - RELATIVE CONTRIBUTION OF OBESITY, OBESITY TYPE, AND DURATION OF OBESITY

Insulin secretion in response to an oral glucose tolerance test (OGTT) and sex hormone levels (free testosterone, androstenedione, dehydroep iandrosterone sulfate [DHEAS], estradiol, and sex hormone-binding glob ulin [SHBG]) were evaluated in 49 healthy obese premenopausal women (b ody mass index [BMI], 30 to 50.6 kg/m(2)) and 21 control subjects (BMI , 17.8 to 24.0 kg/m(2)) with normal glucose tolerance and without sign s of hyperandrogenism. Obese women were divided into two groups accord ing to waist to hip ratio (WHR): 27 subjects with upper-body obesity ( WHR > 0.85) and 22 subjects with lower-body obesity (WHR < 0,8), Both fasting and glucose-induced insulin levels were higher in women with u pper-body obesity than in controls (P < .001) and those with lower-bod y obesity (P < .001). Hyperandrogenism was observed in women with uppe r-body obesity, as evident by significantly elevated free testosterone (P < .05 v controls and subjects with lower-body obesity) and decreas ed SHBG (P < .001 v controls). The most important independent determin ants of fasting insulin levels were BMI (P < .01) and the ratio of DHE AS to free testosterone (P < .01). The most important determinants of cumulative insulin response were WHR (P < .0005), duration of obesity (P < .01), and androstenedione levels (P < .01). In conclusion, in hea lthy obese premenopausal women without clinical signs of hyperandrogen ism, a high BMI and more pronounced upper-body fat localization result ed in hyperinsulinemia and hyperandrogenism. The duration of obesity e xaggerated the glucose-induced insulin level and cumulative insulin re sponse independently of the degree of obesity and obesity type. The ra tio of DHEAS to free testosterone was an independent determinant of fa sting insulin concentration. Furthermore, the ratio of DHEAS to free t estosterone rather than either of these androgens alone may be importa nt in the regulation of insulin action in women. Copyright (C) 1998 by W.B. Saunders Company.