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 estrogen-sensitive tissues as a function of obesity and body fat.
Eighty premenarchal girls (26 OB, 54 NW), aged 8.2–14.7 years, underwent dual-energy x-ray 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, BA), 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.
When controlling for breast morphological stage determined by ultrasound, %BF was not associated with serum estrogen or gonadotropin (LH and FSH) levels or with indices of systemic estrogen action (uterine volume, endometrial thickness, BA 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.
These studies do not support the hypothesis that estrogen derived from total body fat or local (mammary) fat contributes to breast development in OB girls.
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We thank and acknowledge the staff of the CRU, Wake Radiology, and Social and Scientific Systems, Inc. for their support in conducting these studies. We thank Dr. Deborah C. terMeulen (Breast Imaging Division, Massachusetts General Hospital) for assistance with breast ultrasound imaging and interpretation and Paul Kim (Battelle) for technical assistance. We thank Dr. Janet E. Hall for her helpful discussions and careful review of the manuscript.
This work was supported, in part, by the Intramural Research Program of the NIH, NIEHS (Z01-ES103315) and by Grant Number 1UL1TR001102. NDS is also supported as a Lasker Clinical Research Scholar (1SI2ES025429-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Center for Advancing Translational Science or the National Institutes of Health. The findings and conclusions in this paper have not been formally disseminated by the Centers for Disease Control and Prevention, the Agency for Toxic Substances and Disease Registry, and should not be construed to represent any agency determination or policy. Use of trade names and commercial sources is for identification only and does not constitute endorsement by the U.S. Department of Health and Human Services or the U.S. Centers for Disease Control and Prevention.
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