Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls

Abstract

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 >or= 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 <or= 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.

Figure 1. Graphical representation of observed differences between obese and normal weight girls grouped by Tanner stage

Data are presented as mean ± SEM. Differences are assessed with Wilcoxon rank sum tests and are also denoted in Table 1. * P < 0.05, ** P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001 prior to Bonferroni correction. Conversion from conventional to SI units: total T × 3.47 (nmol/liter); insulin × 7.18 (pmol/liter); DHEAS × 27.21 (nmol/liter).

Figure 2. Proportion of normal weight and obese girls with hyperandrogenemia

The normal range for free T was established for each Tanner stage grouping as the range observed in normal weight girls with no evidence of hirsutism (and no irregular periods in girls at least 2 y postmenarche). Fisher’s exact test was employed to compare the proportions with elevated free T within each Tanner stage grouping.

Figure 3. Overnight changes in sex steroid concentrations (Tanner 1–3)

Data are presented as mean ± SEM. Differences between time points were assessed via Wilcoxon sign rank tests: * P ≤ 0.001 (concentrations at approximately 0600 vs. 2300 h). Differences between normal weight (left panel; n = 17) and obese girls (right panel; n = 6) were assessed via Wilcoxon rank sum tests: a = P < 0.05 (normal weight vs. obese at same time point). Conversion from conventional to SI units: P × 3.18 (pmol/L); total T × 3.47 (pmol/L); E₂ × 3.671 (pmol/L).