A number of pathophysiological mechanisms underlie the polycystic ovary syndrome (PCOS). Neuroendocrine abnormalities play a significant role in most women with PCOS, and PCOS is associated with relative resistance of the gonadotropin releasing hormone (GnRH) pulse generator to negative feedback by progesterone and estradiol. This hypothalamic resistance to negative feedback appears to be a result of hyperandrogenemia (HA), and can also occur in adolescents with HA. We have hypothesized that peripubertal HA (which can represent a forerunner of adult PCOS) can promote the development of PCOS in part via induction of hypothalamic resistance to negative feedback. However, the cause of peripubertal HA remains largely unknown. Obesity is a well-recognized pathophysiological factor in the HA of adult PCOS; and recent data demonstrate that peripubertal obesity is associated with HA. However, the mechanisms underlying the relationship between peripubertal obesity and HA—and the marked variability of androgen levels observed among obese girls—are unknown. We have gathered preliminary data that suggests that obese pre- and early pubertal girls with high androgen levels also exhibit greater degrees of insulin resistance compared to obese girls with lower androgens.