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Obesity and Sex Steroid Changes across Puberty: Evidence for Marked Hyperandrogenemia in Pre- and Early Pubertal Obese Girls

The Center for Research in Reproduction (C.R.M., S.K.B., K.A.P., S.Ch., C.A.E., K.D.H., J.C.M.) and Division of Endocrinology (C.R.M., S.K.B., K.A.P., S.Ch., C.A.E., K.D.H., J.C.M.), Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia 22908; Division of Reproductive Endocrinology and Infertility (R.Y., R.J.C.), Department of Reproductive Medicine, University of California, San Diego, San Diego, California 92103; Division of Endocrinology (C.M.F.), Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108; and Department of Pediatrics (S.Ca.), Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Christopher R. McCartney, Center for Research in Reproduction, Box 800391, University of Virginia Health System, Charlottesville, Virginia 22908. E-mail: cm2hq{at}virginia.edu.

Context: Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear.

Objective: The objective of the study was to assess the degree of hyperandrogenemia across puberty in obese girls and assess overnight sex steroid changes in Tanner stage 1–3 girls.

Design: This was a cross-sectional analysis.

Setting: The study was conducted at general clinical research centers.

Subjects: Thirty normal-weight (body mass index for age < 85%) and 74 obese (body mass index for age 95%) peripubertal girls.

Intervention: Blood samples (circa 0500–0700 h) were taken while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1–3 girls.

Main Outcome Measures: Hormone concentrations stratified by Tanner stage were measured.

Results: Compared with normal-weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, whereas fasting insulin was 3-fold elevated in obese Tanner 1–3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05) but not in more mature girls. In a subgroup of normal-weight Tanner 1–3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P 0.001). In obese Tanner 1–3 girls (n = 6), evening P and T were elevated, and both tended to increase overnight [mean 1.4- and 1.6-fold, respectively (P = 0.06)].

Conclusions: Peripubertal obesity is associated with hyperandrogenemia and hyperinsulinemia throughout puberty, being especially marked shortly before and during early puberty. P and T concentrations in normal-weight Tanner 1–3 girls increase overnight, with similar but less evident changes in obese girls.

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