Endocrinology and metabolism after premature pubarche in girls

The prevalence of functional ovarian hyperandrogenism, hyperinsulinism and dyslipidaemia is increased in adolescent girls with a history of premature pubarche, defined as the appearance of pubic hair before the age of 8 years. The ovarian hyperandrogenism is characterized by clinical signs of androgen excess and an exaggerated ovarian 17-hydroxyprogesterone response to gonadotrophin-releasing hormone agonist stimulation. The hyperinsulinism and dyslipidaemia are detectable before and during pubertal development, and they are commonly accompanied by low serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) and sex hormone binding globulin, and by an increased prevalence of anovulation from late adolescence onwards. In girls, premature pubarche, hyperinsulinism, low serum levels of IGFBP-1, dyslipidaemia, anovulation and hyperandrogenism (or various combinations of these conditions) have been related to reduced fetal growth, indicating that these constellations or sequences may have a prenatal origin. These findings suggest that premature pubarche in girls should no longer be regarded as merely a normal variant of development, but rather as a childhood marker pointing to an increased risk of a polyendocrine-metabolic disorder of prenatal origin.