Estrogens and Their Genotoxic Metabolites Are Increased in Obese Prepubertal Girls

TitleEstrogens and Their Genotoxic Metabolites Are Increased in Obese Prepubertal Girls
Publication TypeJournal Article
Year of Publication2015
AuthorsMauras, N., Santen R. J., Colón-Otero G., Hossain J., Wang Q., Mesaros C., & Blair I. A.
JournalThe Journal of clinical endocrinology and metabolism
Volume100
Issue6
Pagination2322-8
Date Published2015 Jun
ISSN1945-7197
KeywordsCase-Control Studies; Child; Estradiol; Estradiol Congeners; Estriol; Estrogens; Estrone; Female; Humans; Mutagens; Pediatric Obesity; Puberty; Thinness; Up-Regulation
Abstract

CONTEXT: Estrogen levels and their metabolites are higher in obese vs lean postmenopausal women, and obesity increases breast cancer risk. Quinone derivatives of 4-hydroxylated estrogen metabolites, independently of the estrogen receptor, cause depurination and impaired DNA repair (genotoxic). 16α-Hydroxy (16α-OH)-estrone (E1), eg, promotes tumor proliferation and 2-methoxy-estradiol (E2) may be chemoprotective. Childhood obesity increases breast cancer death risk in women, but levels of estrogen derivatives had not been previously studied in young children.
OBJECTIVE: The objective of the study was to investigate whether total and genotoxic estrogens are increased in prepubertal obese girls compared with lean controls.
DESIGN: Stored sera from 12 lean and 23 obese prepubertal girls (Tanner stage I breast and pubic hair) studied previously were assayed for E1, E2, and their multiple metabolites (12 steroids total) using highly sensitive liquid chromatography and tandem mass spectrometry.
RESULTS: E2 concentrations were significantly higher in obese [3.45 (0.5, 4.65) pg/ml (median [quartile 1, quartile 3])] vs lean girls [0.5 (0.5, 2.37), P = .04], 57% of values upper quartile or greater (quartile 3) of controls. Concentrations of 16α-OH-E1 were higher in obese [7.17 (0.5, 9.64) pg/mL] vs lean girls [0.5 (0.5, 1.72, P = .007)], 65% of values quartile 3 or greater of controls. 2-Methoxy-E2 concentrations were lower in the obese group (P = .012). 16α-OH-E1 concentrations were positively correlated with body mass index, percentage fat mass, and IL-6 concentrations (P < .001).
CONCLUSIONS: E2 and genotoxic metabolites were higher in obese vs lean prepubertal girls. These data suggest that obesity is associated with an increased extraglandular estrogen production and metabolism before the onset of puberty in girls. Long-term epidemiological studies are needed to assess any potential increase in breast cancer risk.





DOI10.1016/S1081-1206(10)60082-8
Alternate JournalJ. Clin. Endocrinol. Metab
Refereed DesignationRefereed