Background Epidemiologic studies demonstrated that overweight/obese girls (OW/OB) undergo thelarche and menarche earlier than normal weight girls (NW). There have been no longitudinal studies to specifically investigate how body weight/fat affects both clinical and biochemical pubertal markers in girls. Methods 90 girls (36 OW/OB, 54 NW), aged 8.2–14.7 years, completed 2.8 ± 1.7 study visits over the course of four years. Visits included dual-energy x-ray absorptiometry to calculate total body fat (TBF), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and assessment of menarchal status. The effect of TBF on pubertal markers was determined using a mixed, multi-state, or Cox proportional hazards model, controlling for baseline BMORPH. Results NW were older than OW/OB (11.3 vs. 10.2 yrs, p<0.01) at baseline and had more advanced BMORPH (p<0.01). LH, estradiol, and ovarian and uterine volumes increased with time with no effect of TBF. There was a time x TBF interaction for FSH, inhibin B, estrone, total and free testosterone, and androstenedione: levels were initially similar, but after 1 yr, levels increased in girls with higher TBF, plateaued in girls with mid-range TBF, and decreased in girls with lower TBF. Girls with higher TBF progressed through BMORPH stage D more slowly but achieved menarche earlier than girls with lower TBF. Conclusions In late puberty, girls with higher TBF demonstrate differences in standard hormonal and clinical markers of puberty. Investigation of the underlying causes and clinical consequences of these differences in girls with higher TBF deserves further study.

Background-Girls who are overweight/obese (OB) develop breast tissue but do not undergo menarche (the first menstrual period) significantly earlier than girls of normal weight (NW). It has been proposed that estrogen synthesized by adipose tissue may be contributory, yet OB do not have higher serum estrogen levels than NW matched on breast stage. We hypothesized that estrogen synthesized locally, in mammary fat, may contribute to breast development. This hypothesis would predict that breast development would be more advanced than other estrogensensitive tissues as a function of obesity and body fat. Methods-80 pre-menarchal girls (26 OB, 54 NW), aged 8.2-14.7 yrs, underwent dual-energy xray absorptiometry to calculate percent body fat (%BF), Tanner staging of the breast, breast ultrasound for morphological staging, trans-abdominal pelvic ultrasound, hand x-ray (bone age), a blood test for reproductive hormones, and urine collection to determine the vaginal maturation index (VMI), an index of estrogen exposure in urogenital epithelial cells. Results-When controlling for breast morphological stage determined by ultrasound, %BF was not associated with serum estrogen or gonadotropin (LH and FSH) levels or on indices of systemic estrogen action (uterine volume, endometrial thickness, bone age advancement, and VMI). Tanner breast stage did not correlate with breast morphological stage and led to misclassification of chest fatty tissue as breast tissue in some OB. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Background: Studies comparing the timing and pace of puberty in overweight/obese girls (OW/OB) vs normal weight girls (NW) have produced conflicting results; some suggest earlier activation of the central components of the reproductive axis in OB while others are more consistent with a peripheral source of estrogen (e.g. adipose tissue) driving puberty in OB. Importantly, there have been no longitudinal assessments of both clinical and biochemical pubertal markers in OB vs. NW. Methods: 90 healthy pre-menarchal girls (26 OW/OB, 54 NW) from the community, aged 8.2-14.7 years, completed 2.8 ± 1.7 (mean, SD) study visits over the course of 4 years. Visits included dual-energy x-ray absorptiometry to calculate percent total body fat (TBF), Tanner staging, breast ultrasound for morphological staging (BMORPH; stages A-E), pelvic ultrasound, hand x-ray (bone age, BA), blood tests for reproductive hormones, and urine collection to determine a vaginal maturation index (VMI), an index of estrogen exposure in urogenital epithelial cells. Menarchal status was determined at each visit and via follow-up questionnaires. The effect of TBF on hormones and markers of estrogen action, the pace of breast maturation, and age at menarche were determined using a mixed, multi-state, or Cox proportional hazards model, respectively. Mixed and Cox models controlled for BMORPH at visit 1 (V1) and race. Results: NW girls were older than OW/OB (11.3 vs. 10.2 yrs, p<0.01) at V1, more likely to be non-Hispanic White (66 vs. 40%, p=0.03), and had more advanced breast morphology BMORPH (p<0.01). LH, E2, VMI, BA, and ovarian and uterine volume increased with time with no effect of TBF. There was an interaction between time and TBF for FSH, INHB, E1, Total T, Free T, and A’dione (p<0.05): levels were initially similar in all TBF groups, but after 1 yr, levels increased in girls with higher TBF, plateaued in girls with mid-range TBF, and decreased in girls with lower TBF. Girls with higher TBF progressed through BMORPH stage D (corresponding to growth/arborization of the breast ductal system), more slowly than girls with lower TBF but achieved menarche at a younger age (risk 1.04x higher per 1 unit increase in TBF). Conclusions: Intensive reproductive phenotyping of girls during the pubertal transition reveals that both the neuroendocrine and ovarian components of the axis are generally preserved in girls with higher TBF but that the axis appears to be activated earlier than in girls with lower TBF. In late puberty, however, girls with higher TBF demonstrate subtle differences in standard hormonal (e.g. serum FSH, INHB, and androgen) and clinical (e.g. delayed growth of breast bud) markers of puberty. Investigation of the mechanistic basis for these differences and their potential clinical consequences for girls with higher TBF deserves further study.