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Increased estrogen levels, metabolism linked to obesity in prepubescent girls
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Prepubescent girls with obesity have significantly higher estrogen and genotoxic metabolite levels than girls with lean BMI, according to research in The Journal of Clinical Endocrinology & Metabolism.
Research also showed girls with obesity have lower concentrations of 2-methoxyestradiol (2-MeO-E₂) compared with lean controls, a compound that in postmenopausal women has been shown to have chemoprotective and antiproliferative effects in breast cancer cells, according to researchers.
“These results are remarkable as they represent the first line of evidence in humans that genotoxic concentrations of estrogen metabolites can be detected before the onset of puberty and that these concentrations are higher in obese girls,” the researchers wrote.
Nelly Mauras, MD, chief of the division of endocrinology, diabetes and metabolism at Nemours Children’s Health System in Jacksonville, Florida, and colleagues at other institutions analyzed data from 35 prepubertal girls who either had obesity (n = 23) or were lean (n = 12). Researchers measured parent estrogens, estrone, estradiol and their multiple metabolites (12 steroids total), using new, sensitive isotope dilution liquid chromatography–tandem mass spectrometry (LC-MS) estrogen assays developed by study researcher Ian Blair, MD, of the University of Pennsylvania.
Nelly Mauras
Participants with obesity showed higher total estradiol concentrations vs. participants with a lean BMI (P = .04), as well as a higher concentration of 16-alpha-hydroxyestrone (P = .007), a potentially carcinogenic estrogen in postmenopausal women. In contrast, 2-MeO-E₂ was lower in participants with obesity (P = .012). The 16-alpha-hydroxyestrone concentrations were linked to BMI, percentage of fat mass and interleukin-6 concentrations (P < .001).
“The interactions between estrogen metabolites from the fat cells and inflammatory cytokines represent a potentially unhealthy milieu in young prepubertal girls,” Mauras told Endocrine Today. “The long-term consequences of these findings require further study. We would like to confirm these findings in larger cohorts and investigate whether these metabolites can be influenced by targeted interventions for early onset obesity.”
The results echo similar findings related to postmenopausal women that showed an increased accumulation of genotoxic metabolites in breast cancer tumors, according to researchers.
“These data, made possible by new generation assay methodology, suggest that extraglandular estrogen production and metabolism occurs even before the onset of puberty in females,” the researchers wrote. “The changes observed in the [girls with obesity] raise caution about the potential for increased breast cancer risk due to these effects. Long-term epidemiologic studies will now be required to assess this potential risk.” – by Regina Schaffer
Disclosure: Mauras reports receiving grant support (2010 to 2015) from AstraZeneca, Novartis and Pfizer. Please see the full study for a list of the other authors’ relevant financial disclosures.
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