IntroductIonPolycystic ovary syndrome (PCOS) may be the most common endocrine disorder of young women, affecting ~7% of women in their reproductive years (1). Hallmarks of PCOS include ovarian hyperandrogenemia (HA) and ovulatory dysfunction (2,3). The etiology of PCOS remains unclear, but hyperinsulinemia, neuroendocrine abnormalities (e.g., exaggerated luteinizing hormone (LH) secretion), and primary abnormalities of ovarian steroidogenesis have all been proposed as causes (4-6).Manifestations of PCOS often begin soon after menarche, and HA during adolescence can be a precursor of adult PCOS (7,8). However, the cause(s) of adolescent HA is (are) unclear. Obesity is a well-recognized factor in the HA of adult PCOS (9); and some (10-12) but not all (13) studies suggest that obesity is linked to HA in peripubertal girls. Therefore, obesity during the pubertal transition may be an important factor contributing to adolescent and adult PCOS (14). Although mechanisms underlying the relationship between peripubertal obesity and HA remain uncertain, early data suggest that differences of insulin and LH contribute to free testosterone (T) differences between obese and nonobese girls (11,12).Of special interest, not all peripubertal obese girls demonstrate elevated free T (12,13), suggesting that obesity per se is not sufficient to produce HA. Herein we present data that demonstrates marked variability of free T among obese girls. Furthermore, to assess potential determinants of free T elevations in obese girls, we evaluated the relationship between free T and both fasting insulin and morning LH, while simultaneously adjusting for differences in age, pubertal development, and gender-specific BMI z-score. Our primary hypotheses were that insulin and LH would be independent predictors of free T levels in obese girls. Methods and Procedures subjectsOur collaborative group collected hormonal and anthropometric data from obese girls across the pubertal spectrum. Volunteers were recruited from Endocrinology Clinics and via local advertisements and evaluated at the University of Virginia (n = 61), the University of California at San Diego (n = 8), and Yale (n = 23). Gender-specific BMI-for-age percentile (BMI%) and BMI z-score was calculated for each participant using a SAS program incorporating normative data from the National Health and Nutrition Examination Surveys

In insulin-resistant obese girls with hyperinsulinemia, free testosterone levels correlated positively with insulin sensitivity and, likely, circulating LH concentrations but not with circulating insulin levels. In the setting of relatively uniform hyperinsulinemia, variable steroidogenic-cell insulin sensitivity may correlate with metabolic insulin sensitivity and contribute to variable free testosterone concentrations.

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