Evidence map›Paper›PMID 36195867›Full record

SynthesisBMC medicine2022

Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data.

Sean M Hughes, Claire N Levy, Ronit Katz, Erica M Lokken, Melis N Anahtar, Melissa Barousse Hall, Frideborg Bradley, Philip E Castle, Valerie Cortez, Gustavo F Doncel and 26 more

Open access · goldAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 18% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  6. T-Cell Biology in the Female Reproductive Tract: Relevance to HIV Infection.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  7. Article
  8. Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Observational
  18. Article
  19. Article
  20. HIV-Associated Genital Immune Biomarkers in the Female Sex Worker Population: A Pilot Study.American journal of reproductive immunology (New York, N.Y. : 1989) · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors at 20 institutions in 7 countries.

Sean M HughesDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Claire N LevyDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Ronit KatzDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Erica M LokkenDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.
Melis N AnahtarRagon Institute of MIT and Harvard, Massachusetts General Hospital, Boston, MA, USA.
Melissa Barousse HallUniversity of Louisville, Louisville, KY, USA.
Frideborg BradleyDepartment of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Philip E CastleDivision of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
Valerie CortezDepartment of Molecular, Cell & Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA.
Gustavo F DoncelCONRAD, Eastern Virginia Medical School, Norfolk, VA, USA.
Raina FichorovaDepartment of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Paul L FidelLouisiana State University Health, New Orleans, LA, USA.
Keith R FowkeDepartment of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
Suzanna C FrancisMRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK.
Mimi GhoshDepartment of Epidemiology, The George Washington University, Washington, DC, USA.
Loris Y HwangDepartment of Pediatrics, University of California, Los Angeles, Los Angeles, CA, USA.
Mariel JaisOffice of Laboratory Safety, The George Washington University, Washington, DC, USA.
Vicky JespersInstitute of Tropical Medicine, Antwerp, Belgium.
Vineet JoagDepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
Rupert KaulDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada.
Jordan KyongoVirology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Timothy LaheyUniversity of Vermont Larner College of Medicine, Burlington, VT, USA.
Huiying LiDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA.
Julia MakindeIAVI Human Immunology Laboratory, Imperial College, London, England, UK.
Lyle R McKinnonDepartment of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
Anna-Barbara MoscickiDepartment of Pediatrics, University of California, Los Angeles, Los Angeles, CA, USA.
Richard M NovakUniversity of Illinois, Chicago, IL, USA.
Mickey V PatelGeisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Intira SriprasertDepartment of OB/GYN, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Andrea R ThurmanCONRAD, Eastern Virginia Medical School, Norfolk, VA, USA.
Sergey YegorovDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Nelly Rwamba MugoDepartment of Global Health, University of Washington, Seattle, WA, USA.
Alison C RoxbyDepartment of Global Health, University of Washington, Seattle, WA, USA.
Elizabeth MicksDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA. emicks@uw.edu.
Florian HladikDepartment of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA. florian@uw.edu.ORCID 0000-0002-0375-2764
Consortium for Assessing Immunity Across the Menstrual Cycle
University of Washington · USUniversity of California, Los Angeles · USEastern Virginia Medical School · USGeorge Washington University · USInstituut voor Tropische Geneeskunde · BEInternational AIDS Vaccine Initiative · USUniversity of Illinois Chicago · USUniversity of Minnesota · USBrigham and Women's Hospital · USDartmouth College · USInfectious Disease Research Institute · USKarolinska University Hospital · SELondon School of Hygiene & Tropical Medicine · GBLouisiana State University Health Sciences Center New Orleans · USMcMaster University · CANational Institutes of Health · USRagon Institute of MGH, MIT and Harvard · USUniversity of California, Santa Cruz · USUniversity of Louisville · USUniversity of Manitoba · CA

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 1988 to 2026
$104.9M
THE PERINATAL COMPLICATIONS OF ASYMPTOMATIC GENITAL HERPES SIMPLEX VIRUSP01AI030731 · NIAID · UNIVERSITY OF WASHINGTON · PI ZHU, JIA · 1991 to 2017
$34.3M
DENDRITIC AND T CELLS IN ANTI-BACTERIAL lg RESPONSESR01AI049192 · NIAID · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI SNAPPER, CLIFFORD M · 2001 to 2010
$2.9M
Impact of Aging on Mucosal Immune Protection in the Female ReproductiveR01AG064794 · NIA · DARTMOUTH COLLEGE · PI WIRA, CHARLES ROBERT · 2019 to 2023
$2.8M
Incident STIs in Kenyan Girls: a prospective cohort spanning sexual debutR01HD091996 · NICHD · UNIVERSITY OF WASHINGTON · PI ROXBY, ALISON CHRISTINA · 2017 to 2020
$1.4M
Cervicovaginal immune factors throughout the menstrual cycle: analysis of a cohort of Kenyan adolescents, systematic review, and meta-analysisR03AI154366 · NIAID · UNIVERSITY OF WASHINGTON · PI HLADIK, FLORIAN · 2020 to 2021
$177k
Medical Research Council G0901756NIAID NIH HHS P01 AI030731NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI049192NIAID NIH HHS R03 AI154366NIA NIH HHS R01 AG064794NICHD NIH HHS R01 HD091996NIH HHS P51 OD011092
6 · The paper itself

Abstract

backgroundHormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence.

methodsWe performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples.

resultsWe screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here.

conclusionsDespite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.

Indexed as

beta-DefensinsElafinFemaleGranulocyte Colony-Stimulating FactorHumansImmunoglobulinsImmunologic FactorsInterferonsInterleukin-16Interleukin-1alphaInterleukin 1 Receptor Antagonist ProteinInterleukin-6InterleukinsLactoferrinMenstrual CycleMuramidasebeta-DefensinsElafinGranulocyte Colony-Stimulating FactorImmunoglobulinsImmunologic FactorsInterferonsInterleukin-16Interleukin-1alphaInterleukin 1 Receptor Antagonist ProteinInterleukin-6InterleukinsLactoferrinMuramidaseProgesteroneCervixChemokineCytokineFemale genital tractMenstrual cycleMeta-analysisSystematic reviewvagina

Identifiers

PMID36195867
PMCPMC9533580
OpenAlexW4301370325

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.