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Cited by 55Hypothalamic control of reproductive hormonesReproductive Biology and FertilityOvarian function and disorders

Healthy post-menarchal adolescent girls demonstrate multi-level reproductive axis immaturity

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Sun, Bob Z, Kangarloo, Tairmae, Adams, Judith M, Sluss, Patrick M, Welt, Corrine K, Chandler, Donald W, Zava, David T, McGrath, John A +3 more·2019·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2018-00595PMC PMC6325170
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Abstract

Context: Menstrual irregularity after menarche has been attributed to immature estrogen positive feedback activity (E+FB) but data are conflicting. Objective: To determine the hypothalamic-pituitary-ovarian contributions to menstrual irregularity in adolescents. Methods: Twenty-three healthy girls [aged 12.8 to 17.6 years; 0.4 to 3.5 years postmenarche; body mass index (BMI) percentile, 41.0 to 99.3] underwent serial hormone measurements and pelvic ultrasounds during two consecutive menstrual cycles. Hormones and follicle growth were compared with 65 adult historic controls with ovulatory cycles (OVs). Results: Girls had anovulatory cycles (ANOVs; 30%), OVs with a short luteal phase (short OVs; 22%), or OVs with normal luteal phase (normal OVs; 48%) without differences in cycle length, chronologic or gynecologic age, or BMI. Adolescents showed a spectrum of E+FB [midcycle LH adjusted for preovulatory estradiol (E2)]; only normal OV girls were comparable to adults. All OV girls had lower E2, progesterone, and gonadotropins during the luteal phase and luteal-follicular transition compared with adults. Normal OV girls also had lower follicular phase LH and FSH levels, a longer follicular phase, a slower dominant follicle growth rate, and smaller estimated preovulatory follicle size than adults. Follicular phase E2 and inhibin B levels were lower in normal OV girls than in adults even after adjusting for differences in FSH and follicle size. Conclusions: Early postmenarchal girls with normal OVs demonstrate mature E+FB but continue to have lower gonadotropin levels, diminished ovarian responsiveness, and decreased corpus luteum sex steroid synthesis compared with adults, indicating that reproductive axis maturity requires coordinated development of all components of the hypothalamic-pituitary-ovarian axis.

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  • Coordinated development of all components of the HPO axis may take up to 5 years postmenarche.

    “A pilot study entailing serial hormone concentrations and ultrasound studies in ovulatory postmenarcheal girls revealed lower steroid (estrogen and progesterone) concentrations, slower dominant follicle growth rate, and longer follicular phases compared with adult women; these data suggest that coordinated development of all components of the HPO axis may take up to 5 years postmenarche [136, 137]”

    From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [136]

  • A pilot study entailing serial hormone concentrations and ultrasound studies in ovulatory postmenarcheal girls revealed lower steroid (estrogen and progesterone) concentrations, slower dominant follicle growth rate, and longer follicular phases compared with adult women.

    “A pilot study entailing serial hormone concentrations and ultrasound studies in ovulatory postmenarcheal girls revealed lower steroid (estrogen and progesterone) concentrations, slower dominant follicle growth rate, and longer follicular phases compared with adult women; these data suggest that coordinated development of all components of the HPO axis may take up to 5 years postmenarche [136, 137]”

    From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [136]

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2 of the 75 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Doring GK. The incidence of anovular cycles in women. J Reprod Fertil. 1969;6:77-81.
  2. Feicht CB, Johnson TS, Martin BJ, Sparkes KE, Wagner WW Jr. Secondary amenorrhoea in athletes. Lancet. 1978;2(8100):1145- 1146.

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Authors
Sun, B. Z., Kangarloo, T., Adams, J. M., Sluss, P. M., Welt, C. K., Chandler, D. W., Zava, D. T., McGrath, J. A., Umbach, D. M., Hall, J. E., & Shaw, N. D.
Affiliations
  • National Institutes of Health (US)
  • Massachusetts General Hospital (US)
  • University of Utah (US)
  • Endocrine Sciences, Laboratory Corp, Calabasas Hills, California
  • ZRT Laboratory (US)
  • Social and Scientific Systems (United States) (US)
Corresponding author
Shaw, Natalie D
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2018-10-04
Volume
104
Issue
2
Pages
613-623
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2018-00595
PMC
PMC6325170
OpenAlex
W2895146499
Cited by
55
References
75
Citations by year
2026: 5 · 2025: 8 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 7 · 2020: 3 · 2019: 5
FWCI
4.00
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Environmental Health Sciences (Z01-ES103315)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Keywords
menstrual irregularity, estrogen positive feedback, hypothalamic-pituitary-ovarian axis, anovulatory cycles, short luteal phase, ovarian follicle development, gonadotropins, inhibin B
MeSH terms
Adolescent, Adult, Child, Estradiol, Female, Follicle Stimulating Hormone, Humans, Hypothalamo-Hypophyseal System, Inhibins, Luteinizing Hormone, Menarche, Menstrual Cycle, Ovary, Ovulation, Progesterone, Cohort Studies, Adolescent Development

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