Androgens May Mediate a Relative Preservation of IGF-I Levels in Overweight and Obese Women Despite Reduced Growth Hormone Secretion

Abstract

Obesity is characterized by reduced GH secretion, but data regarding IGF-I levels and their determinants are conflicting. The objectives were to determine whether IGF-I levels are reduced and to investigate determinants of GH and IGF-I in healthy overweight and obese women. A cross-sectional study was performed. The study was conducted at a General Clinical Research Center. Thirty-four healthy women without pituitary/hypothalamic disease participated, including 11 lean [body mass index (BMI) <25 kg/m(2)], 12 overweight (BMI > or =25 kg/m(2) and <30 kg/m(2)), and 11 obese (BMI > or =30 kg/m(2)) women of comparable age (overall mean age, 30.7 +/- 7.8 yr). There was no intervention. The main outcome measures were frequent sampling (every 10 min for 24 h) for GH, peak GH after GHRH-arginine stimulation, IGF-I, IGF binding protein-3, estrone, estradiol, testosterone, free testosterone, SHBG, homeostasis model assessment of insulin resistance, and abdominal fat. Mean 24-h GH and peak stimulated GH were lower in overweight than lean women and lowest in obese women. Mean IGF-I levels trended lower in obese, but not overweight, compared with lean women. Free testosterone was positively associated with IGF-I (R = 0.36, P = 0.04) but not with GH measures. Visceral fat was the only determinant of mean 24-h GH (R(2) = 0.66, P < 0.0001) and of peak stimulated GH (R(2) = 0.63, P < 0.0001), and mean 24-h GH accounted for 39% of the variability of IGF-I (P = 0.0002), with an additional 28% (P < 0.0001) attributable to free testosterone levels. Despite a linear decrease in GH secretion and peak stimulated GH levels with increasing BMI in healthy overweight and obese women, IGF-I levels were not commensurately reduced. Androgens may contribute to this relative preservation of IGF-I secretion in overweight and obese women despite reduced GH secretion.