The relationship between ovarian structure and serum insulin, insulin-like growth factor-I (IGF-I) and its binding protein (IGFBP-1 and IGFBP-3) levels in premature pubarche

Abstract

The aim of this study was to determine serum insulin, insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBP-1 and IGFBP-3) levels and their relationship with androgen levels and ovarian structure in 23 girls with premature pubarche (PP). Fasting levels of testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), androstenedione (delta4A), sex hormone binding globulin (SHBG), glucose (G), insulin (I), IGF-I, IGFBP-1, IGFBP-3 were measured. Androgens or steroid hormone levels > 3 SD of normal postpubertal levels were considered as an exaggerated response to the ACTH test. The fasting I to G ratio (FIGR) was calculated and FIGR > 22 was suggestive of insulin resistance (IR). A pelvic ultrasound (US) was carried out and the ovarian structure was divided into five classes (c): c1--homogeneous, c2--microcystic, c3--multicystic, c4--polycystic and c5--follicular. The girls with PP were divided into two groups according to the main ovarian classes observed: PPc1 (n = 6) and PPc2 (n = 15). The FIGR showed IR in 44% of patients. The androgens, SHBG, G, I, FIGR, IGF-I and IGFBP-1 levels were similar among the groups (PPc1 vs PPc2). An exaggerated response to ACTH was more common and IGFBP-3 levels were higher in the PPc2 than in the PPc1 group (p = 0.04). Regression analysis revealed that I was correlated with DHEAS (r = -0.43, p = 0.04) and IGFBP-1 (r = -0.51, p = 0.01); IGF-I was correlated with DHEA (r = -0.42, p = 0.05), delta4A (r = -0.47, p = 0.02), SHBG (r = -0.43, p = 0.04), IGFBP-1 (r = -0.61, p = 0.002) and IGFBP-3 (r = 0.56, p = 0.005); IGFBP-1 was correlated with SHBG (r = 0.56, p = 0.005). These findings suggest that there might be interactions between the insulin-IGF-I-IGFBPs system and hyperandrogenism. However, the possible causal role of adrenal androgen hypersecretion on the insulin-IGF-I-IGFBPs axis and ovarian structure in girls with PP remains to be established. Since studies reveal that IGFBP-3 levels could be a negative predictor for insulin sensitivity throughout puberty, we hypothesize that girls with PP and microcystic ovaries are at risk of developing IR in the course of normal puberty.