Abstract

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