CoChat
Sign Up
Cited by 56Genetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesSexual Differentiation and DisordersHypothalamic control of reproductive hormones

Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial

Open access
Quigley, Charmian A., Wan, Xiaohai, Garg, Sipi, Kowal, Karen, Cutler, Gordon B., Ross, Judith L.·2014·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2013-4518PMC PMC4154082
Open this paper in CoChat — free account

Abstract

CONTEXT: The optimal approach to estrogen replacement in girls with Turner syndrome has not been determined. OBJECTIVE: The aim of the study was to assess the effects of an individualized regimen of low-dose ethinyl estradiol (EE2) during childhood from as early as age 5, followed by a pubertal induction regimen starting after age 12 and escalating to full replacement over 4 years. DESIGN: This study was a prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: The study was conducted at two US pediatric endocrine centers. SUBJECTS: Girls with Turner syndrome (n = 149), aged 5.0-12.5 years, were enrolled; data from 123 girls were analyzable for pubertal onset. INTERVENTION(S): Interventions comprised placebo or recombinant GH injections three times a week, with daily oral placebo or oral EE2 during childhood (25 ng/kg/d, ages 5-8 y; 50 ng/kg/d, ages >8-12 y); after age 12, all patients received escalating EE2 starting at a nominal dosage of 100 ng/kg/d. Placebo/EE2 dosages were reduced by 50% for breast development before age 12 years, vaginal bleeding before age 14 years, or undue advance in bone age. MAIN OUTCOME MEASURES: The main outcome measures for this report were median ages at Tanner breast stage ≥2, median age at menarche, and tempo of puberty (Tanner 2 to menarche). Patterns of gonadotropin secretion and impact of childhood EE2 on gonadotropins also were assessed. RESULTS: Compared with recipients of oral placebo (n = 62), girls who received childhood low-dose EE2 (n = 61) had significantly earlier thelarche (median, 11.6 vs 12.6 y, P < 0.001) and slower tempo of puberty (median, 3.3 vs 2.2 y, P = 0.003); both groups had delayed menarche (median, 15.0 y). Among childhood placebo recipients, girls who had spontaneous breast development before estrogen exposure had significantly lower median FSH values than girls who did not. CONCLUSIONS: In addition to previously reported effects on cognitive measures and GH-mediated height gain, childhood estrogen replacement significantly normalized the onset and tempo of puberty. Childhood low-dose estrogen replacement should be considered for girls with Turner syndrome.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1210/jc.2013-4518

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • One double-blind placebo-controlled trial demonstrated a modest synergistic increase in adult height, normalization of the timing of thelarche for about one-quarter of girls, and modest improvements in cognition and memory.

    “One double-blind, placebo-controlled trial using ultra-low-dose oral ethinyl estradiol as a growth-promoting agent during the prepubertal period combined with GH, followed by a standardized incremental pubertal induction regimen, demonstrated a modest synergistic increase in adult height, normalization of the timing of thelarche for about one-quarter of the girls, and modest improvements in cogni”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [181]

  • Even ethinyl estradiol, generally not recommended for puberty induction but used in ultra-low doses and gradually increased, resulted in favorable adult height.

    “Even ethinyl estradiol, generally not recommended for puberty induction, but used in ultra-low doses and gradually increased, resulted in favorable adult height.”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [181]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. [25]25. Hamill PW, Drizd TA, Johnson CL, Reed RB, Roche AF. Health examination survey data, NCHS growth charts, 1976. Monthly Vital Statistics Report. 1976;25(suppl 3):1–22 [Google Scholar]
  2. [30]30. Dewhurst CJ, de Koos EB, Haines RM. Replacement hormone therapy in gonadal dysgenesis. Br J Obstet Gynaecol. 1975;82(5):412–416 [DOI] [PubMed] [Google Scholar]
  3. [69]69. Kesler SR. Turner syndrome. Child Adolesc Psychiatr Clin N Am. 2007;16(3):709–722 [DOI] [PMC free article] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Related

Authors
Quigley, C. A., Wan, X., Garg, S., Kowal, K., Cutler, G. B., & Ross, J. L.
Affiliations
  • Indiana University School of Medicine (US)
  • Novartis (United States) (US)
  • GCE Solutions Inc (S.G.), Bloomington, Illinois 61701
  • Thomas Jefferson University (US)
  • Gordon Cutler Consultancy, LLC (G.B.C.), Deltaville, Virginia 23043
Corresponding author
Quigley, Charmian A.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2014-09-01
Volume
99
Issue
9
Pages
E1754-E1764
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2013-4518
PMC
PMC4154082
OpenAlex
W2167700231
Cited by
56
References
75
Citations by year
2024: 4 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 8 · 2016: 5 · 2015: 7 · 2014: 2
FWCI
4.80
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
Turner syndrome, ethinyl estradiol, estrogen replacement therapy, pubertal development, puberty induction, gonadotropins, follicle-stimulating hormone, luteinizing hormone, menarche, thelarche, growth hormone, bone age, breast development, puberty timing
MeSH terms
Adolescent, Body Height, Breast, Dose-Response Relationship, Drug, Double-Blind Method, Estrogens, Ethinyl Estradiol, Female, Gonadotropins, Humans, Menarche, Placebos, Puberty, Turner Syndrome, Treatment Outcome, Hormone Replacement Therapy, Kaplan-Meier Estimate, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review