Precocious Pubarche, Hyperinsulinism, and Ovarian Hyperandrogenism in Girls: Relation to Reduced Fetal Growth

Abstract

Pronounced adrenarche with precocious pubarche (PP) in girls has been associated with hyperinsulinism and subsequent functional ovarian hyperandrogenism (FOH). Recently, pronounced adrenarche and insulin resistance have each been related to low birth weight. We have now tested the hypothesis that the frequent concurrence of PP with pronounced adrenarche, FOH, and hyperinsulinemia in girls may be secondary to separate relationships between these conditions and low birth weight. A total of 185 girls (aged 5-18 yr) without endocrinopathy or with PP and pronounced adrenarche with or without FOH were studied; mean serum insulin (MSI) concentrations were determined after a standardized oral glucose tolerance test. Birth weight SD scores [mean (SEM)] of control girls (0.38+/-0.08; n = 83) were higher (P < 0.0001) than those of PP girls (-0.81+/-0.13; n = 102). Among postmenarcheal PP girls, birth weight SD scores of girls without FOH (-0.25+/-0.19; n = 25) were higher (P < 0.0001) than those in girls with FOH (-1.51+/-0.28; n = 23). In pubertal girls (n = 145), MSI levels correlated negatively with birth weight SD scores (r = -0.48; P < 0.05), independently of PP. MSI levels in girls with birth weight below 1 SD (93+/-9 mU/L; n = 33) were higher (P < 0.0001) than those in girls with birth weight between -1 and +1 SD (52+/-2 mU/L; n = 94), whereas glycemia profiles were comparable. Integration of the aforementioned data suggests that there may be a sequence in the associations between reduced fetal growth and components of the postnatal endocrine system; minor fetal growth reduction appears to be associated with amplified adrenarche, whereas more pronounced prenatal growth restriction seem to precede FOH and hyperinsulinemia during adolescence. In conclusion, these findings corroborate the hypothesis that the frequent concurrence of PP (with pronounced adrenarche), FOH, and hyperinsulinemia in girls may result from a common early origin (low birth weight serving as a marker), rather than from a direct interrelationship later in life.