Evidence map›Paper›PMID 25856214›Full record

ArticleThe Journal of clinical endocrinology and metabolism2015

Estrogens and Their Genotoxic Metabolites Are Increased in Obese Prepubertal Girls.

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

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Review
  6. Salivary Sex Steroid Levels in Infants and the Relation with Infantile ColicJournal of clinical research in pediatric endocrinology · 2024
    Article
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  14. Estrogen Metabolism in Premenopausal Women Is Related to Early Life Body Fatness.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018
    Article
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  16. Observational
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Nelly MaurasDivision of Endocrinology, Diabetes, and Metabolism (N.M.), Nemours Children's Health System, Jacksonville, Florida 32207; Division of Endocrinology (R.J.S.), University of Virginia, Charlottesville, Virginia 22908; Division of Hematology and Oncology (G.C.-O.), Mayo Clinic, Jacksonville, Florida 32224; Department of Statistics and Bioinformatics (J.H.), Dupont Hospital for Children, Wilmington, Delaware 19803; and Center for Excellence in Environmental Toxicology (Q.W., C.M., I.A.B.), Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Richard J SantenDivision of Endocrinology, Diabetes, and Metabolism (N.M.), Nemours Children's Health System, Jacksonville, Florida 32207; Division of Endocrinology (R.J.S.), University of Virginia, Charlottesville, Virginia 22908; Division of Hematology and Oncology (G.C.-O.), Mayo Clinic, Jacksonville, Florida 32224; Department of Statistics and Bioinformatics (J.H.), Dupont Hospital for Children, Wilmington, Delaware 19803; and Center for Excellence in Environmental Toxicology (Q.W., C.M., I.A.B.), Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Gerardo Colón-OteroDivision of Endocrinology, Diabetes, and Metabolism (N.M.), Nemours Children's Health System, Jacksonville, Florida 32207; Division of Endocrinology (R.J.S.), University of Virginia, Charlottesville, Virginia 22908; Division of Hematology and Oncology (G.C.-O.), Mayo Clinic, Jacksonville, Florida 32224; Department of Statistics and Bioinformatics (J.H.), Dupont Hospital for Children, Wilmington, Delaware 19803; and Center for Excellence in Environmental Toxicology (Q.W., C.M., I.A.B.), Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Jobayer HossainDivision of Endocrinology, Diabetes, and Metabolism (N.M.), Nemours Children's Health System, Jacksonville, Florida 32207; Division of Endocrinology (R.J.S.), University of Virginia, Charlottesville, Virginia 22908; Division of Hematology and Oncology (G.C.-O.), Mayo Clinic, Jacksonville, Florida 32224; Department of Statistics and Bioinformatics (J.H.), Dupont Hospital for Children, Wilmington, Delaware 19803; and Center for Excellence in Environmental Toxicology (Q.W., C.M., I.A.B.), Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Qingqing WangDivision of Endocrinology, Diabetes, and Metabolism (N.M.), Nemours Children's Health System, Jacksonville, Florida 32207; Division of Endocrinology (R.J.S.), University of Virginia, Charlottesville, Virginia 22908; Division of Hematology and Oncology (G.C.-O.), Mayo Clinic, Jacksonville, Florida 32224; Department of Statistics and Bioinformatics (J.H.), Dupont Hospital for Children, Wilmington, Delaware 19803; and Center for Excellence in Environmental Toxicology (Q.W., C.M., I.A.B.), Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Clementina MesarosDivision of Endocrinology, Diabetes, and Metabolism (N.M.), Nemours Children's Health System, Jacksonville, Florida 32207; Division of Endocrinology (R.J.S.), University of Virginia, Charlottesville, Virginia 22908; Division of Hematology and Oncology (G.C.-O.), Mayo Clinic, Jacksonville, Florida 32224; Department of Statistics and Bioinformatics (J.H.), Dupont Hospital for Children, Wilmington, Delaware 19803; and Center for Excellence in Environmental Toxicology (Q.W., C.M., I.A.B.), Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Ian A BlairDivision of Endocrinology, Diabetes, and Metabolism (N.M.), Nemours Children's Health System, Jacksonville, Florida 32207; Division of Endocrinology (R.J.S.), University of Virginia, Charlottesville, Virginia 22908; Division of Hematology and Oncology (G.C.-O.), Mayo Clinic, Jacksonville, Florida 32224; Department of Statistics and Bioinformatics (J.H.), Dupont Hospital for Children, Wilmington, Delaware 19803; and Center for Excellence in Environmental Toxicology (Q.W., C.M., I.A.B.), Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Translational Therapeutics (United States) · USCommunity Health Systems - Dupont Hospital · USJacksonville College · USNemours Children's Health System · USUniversity of Virginia · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
Development of Breast Cancer Risk Model Based on Estrogen MetabolomicsR01CA158328 · NCI · UNIVERSITY OF VIRGINIA · PI BLAIR, IAN ALEXANDER, HEITJAN, DANIEL FRANCIS · 2012 to 2013
$779k
NCI NIH HHS NCIP50-CA01508NCI NIH HHS R01 CA158328NCI NIH HHS R01CA158328NIEHS NIH HHS P30 ES013508NIEHS NIH HHS P30ES013508
6 · The paper itself

Abstract

contextEstrogen 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.

objectiveThe objective of the study was to investigate whether total and genotoxic estrogens are increased in prepubertal obese girls compared with lean controls.

designStored 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.

resultsE2 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).

conclusionsE2 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.

Indexed as

2-MethoxyestradiolCase-Control StudiesChildEstradiolEstradiol CongenersEstriolEstrogensEstroneFemaleHumansMutagensPediatric ObesityPubertyThinnessUp-Regulation2-MethoxyestradiolEstradiolEstradiol CongenersEstriolEstrogensEstroneMutagens

Identifiers

PMID25856214
PMCPMC4454805
OpenAlexW2066206894

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.