Estrogens and their genotoxic metabolites are increased in obese prepubertal girls

Nelly Mauras, Richard J. Santen, Gerardo Colon-Otero, Jobayer Hossain, Qingqing Wang, Clementina Mesaros, Ian A. Blair

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (E<inf>1</inf>), eg, promotes tumor proliferation and 2-methoxyestradiol (E<inf>2</inf>) 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 E<inf>1</inf>, E<inf>2</inf>, and their multiple metabolites (12 steroids total) using highly sensitive liquid chromatography and tandem mass spectrometry. Results: E<inf>2</inf> 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-E<inf>1</inf> 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-E<inf>2</inf> concentrations were lower in the obese group (P = .012). 16α-OH-E<inf>1</inf> concentrations were positively correlated with body mass index, percentage fat mass, and IL-6 concentrations (P < .001). Conclusions: E<inf>2</inf> 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.

Original languageEnglish (US)
Pages (from-to)2322-2328
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number6
DOIs
StatePublished - Jun 1 2015

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Metabolites
Estrogens
Derivatives
Breast Neoplasms
Estrone
Liquid chromatography
Metabolism
Obesity
Estrogen Receptors
Mass spectrometry
Tumors
Interleukin-6
Repair
Fats
Steroids
Pediatric Obesity
Puberty
Tandem Mass Spectrometry
Liquid Chromatography
DNA Repair

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogens and their genotoxic metabolites are increased in obese prepubertal girls. / Mauras, Nelly; Santen, Richard J.; Colon-Otero, Gerardo; Hossain, Jobayer; Wang, Qingqing; Mesaros, Clementina; Blair, Ian A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 6, 01.06.2015, p. 2322-2328.

Research output: Contribution to journalArticle

Mauras, Nelly ; Santen, Richard J. ; Colon-Otero, Gerardo ; Hossain, Jobayer ; Wang, Qingqing ; Mesaros, Clementina ; Blair, Ian A. / Estrogens and their genotoxic metabolites are increased in obese prepubertal girls. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 6. pp. 2322-2328.
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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-methoxyestradiol (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.",
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T1 - Estrogens and their genotoxic metabolites are increased in obese prepubertal girls

AU - Mauras, Nelly

AU - Santen, Richard J.

AU - Colon-Otero, Gerardo

AU - Hossain, Jobayer

AU - Wang, Qingqing

AU - Mesaros, Clementina

AU - Blair, Ian A.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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-methoxyestradiol (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.

AB - 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-methoxyestradiol (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.

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