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Open Access 01-12-2022 | Cytokines | Registered report

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

Authors: 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, Raina Fichorova, Paul L. Fidel Jr, Keith R. Fowke, Suzanna C. Francis, Mimi Ghosh, Loris Y. Hwang, Mariel Jais, Vicky Jespers, Vineet Joag, Rupert Kaul, Jordan Kyongo, Timothy Lahey, Huiying Li, Julia Makinde, Lyle R. McKinnon, Anna-Barbara Moscicki, Richard M. Novak, Mickey V. Patel, Intira Sriprasert, Andrea R. Thurman, Sergey Yegorov, Nelly Rwamba Mugo, Alison C. Roxby, Elizabeth Micks, Florian Hladik, The Consortium for Assessing Immunity Across the Menstrual Cycle

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

Hormonal 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.

Methods

We 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.

Results

We 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.

Conclusions

Despite 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.

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Wira CR, Rodriguez-Garcia M, Patel MV. The role of sex hormones in immune protection of the female reproductive tract. Nat Rev Immunol. 2015;15(4):217–30.PubMedPubMedCentralCrossRef

Henning TR, Butler K, Hanson D, Sturdevant G, Ellis S, Sweeney EM, et al. Increased susceptibility to vaginal simian/human immunodeficiency virus transmission in pig-tailed macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis. J Infect Dis. 2014;210(8):1239–47.PubMedPubMedCentralCrossRef

Kersh EN, Henning T, Vishwanathan SA, Morris M, Butler K, Adams DR, et al. SHIV susceptibility changes during the menstrual cycle of pigtail macaques. J Med Primatol. 2014;43(5):310–6.PubMedPubMedCentralCrossRef

Vishwanathan SA, Guenthner PC, Lin CY, Dobard C, Sharma S, Adams DR, et al. High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques. J Acquired Immune Def Syndr (1999). 2011;57(4):261–4.CrossRef

Saba E, Grivel JC, Vanpouille C, Brichacek B, Fitzgerald W, Margolis L, et al. HIV-1 sexual transmission: early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model. Mucosal Immunol. 2010;3(3):280–90.PubMedPubMedCentralCrossRef

Szotek EL, Narasipura SD, Al-Harthi L. 17β-Estradiol inhibits HIV-1 by inducing a complex formation between β-catenin and estrogen receptor α on the HIV promoter to suppress HIV transcription. Virology. 2013;443(2):375–83.PubMedCrossRef

Tasker C, Ding J, Schmolke M, Rivera-Medina A, García-Sastre A, Chang TL. 17β-estradiol protects primary macrophages against HIV infection through induction of interferon-alpha. Viral Immunol. 2014;27(4):140–50.PubMedPubMedCentralCrossRef

Al-Harthi L, Kovacs A, Coombs RW, Reichelderfer PS, Wright DJ, Cohen MH, et al. A menstrual cycle pattern for cytokine levels exists in HIV-positive women: implication for HIV vaginal and plasma shedding. AIDS. 2001;15(12):1535–43.PubMedCrossRef

Al-Harthi L, Wright DJ, Anderson D, Cohen M, Matity Ahu D, Cohn J, et al. The impact of the ovulatory cycle on cytokine production: evaluation of systemic, cervicovaginal, and salivary compartments. J Interf Cytokine Res. 2000;20(8):719–24.CrossRef

10.

Boily-Larouche G, Lajoie J, Dufault B, Omollo K, Cheruiyot J, Njoki J, et al. Characterization of the Genital Mucosa Immune Profile to Distinguish Phases of the Menstrual Cycle: Implications for HIV Susceptibility. J Infect Dis. 2019;219(6):856–66.PubMedCrossRef

11.

Bradley F, Birse K, Hasselrot K, Noel-Romas L, Introini A, Wefer H, et al. The vaginal microbiome amplifies sex hormone-associated cyclic changes in cervicovaginal inflammation and epithelial barrier disruption. Am J Reprod Immunol. 2018;80(1):e12863.PubMedCrossRef

12.

Byrne EH, Anahtar MN, Cohen KE, Moodley A, Padavattan N, Ismail N, et al. Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study. Lancet Infect Dis. 2016;16(4):441–8.PubMedCrossRef

13.

Castle PE, Hildesheim A, Bowman FP, Strickler HD, Walker JL, Pustilnik T, et al. Cervical concentrations of interleukin-10 and interleukin-12 do not correlate with plasma levels. J Clin Immunol. 2002;22(1):23–7.PubMedCrossRef

14.

Cortez V, Odem-Davis K, Lehman DA, Mabuka J, Overbaugh J. Quotidian changes of genital tract cytokines in human immunodeficiency virus-1-infected women during the menstrual cycle. Open Forum Infect Dis Ther. 2014;1(1):ofu002.CrossRef

15.

Francis SC, Hou Y, Baisley K, van de Wijgert J, Watson-Jones D, Ao TT, et al. Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection. PLoS One. 2016;11(1):e0143109.PubMedPubMedCentralCrossRef

16.

Gargiulo AR, Fichorova RN, Politch JA, Hill JA, Anderson DJ. Detection of implantation-related cytokines in cervicovaginal secretions and peripheral blood of fertile women during ovulatory menstrual cycles. Fertil Steril. 2004;82(Suppl 3):1226–34.PubMedCrossRef

17.

Gravitt PE, Hildesheim A, Herrero R, Schiffman M, Sherman ME, Bratti MC, et al. Correlates of IL-10 and IL-12 concentrations in cervical secretions. J Clin Immunol. 2003;23(3):175–83.PubMedCrossRef

18.

Hughes BL, Dutt R, Raker C, Barthelemy M, Rossoll RM, Ramratnam B, et al. The impact of pregnancy on anti-HIV activity of cervicovaginal secretions. Am J Obstet Gynecol. 2016;215(6):748, e1–e12.CrossRef

19.

Jais M, Younes N, Chapman S, Cu-Uvin S, Ghosh M. Reduced levels of genital tract immune biomarkers in postmenopausal women: implications for HIV acquisition. Am J Obstet Gynecol. 2016;215(3):324 e1–e10.CrossRef

20.

Jaumdally SZ, Masson L, Jones HE, Dabee S, Hoover DR, Gamieldien H, et al. Lower genital tract cytokine profiles in South African women living with HIV: influence of mucosal sampling. Sci Rep. 2018;8(1):12203.PubMedPubMedCentralCrossRef

21.

Jespers V, Kyongo J, Joseph S, Hardy L, Cools P, Crucitti T, et al. A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa. Sci Rep. 2017;7:13.CrossRef

22.

Keller MJ, Guzman E, Hazrati E, Kasowitz A, Cheshenko N, Wallenstein S, et al. PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity. AIDS. 2007;21(4):467–76.PubMedCrossRef

23.

Kyongo JK, Jespers V, Goovaerts O, Michiels J, Menten J, Fichorova RN, et al. Searching for lower female genital tract soluble and cellular biomarkers: defining levels and predictors in a cohort of healthy Caucasian women. PLoS One. 2012;7(8):e43951.PubMedPubMedCentralCrossRef

24.

Luo L, Ibaragi T, Maeda M, Nozawa M, Kasahara T, Sakai M, et al. Interleukin-8 levels and granulocyte counts in cervical mucus during pregnancy. Am J Reprod Immunol. 2000;43(2):78–84.PubMedCrossRef

25.

Macneill C, de Guzman G, Sousa GE, Umstead TM, Phelps DS, Floros J, et al. Cyclic changes in the level of the innate immune molecule, surfactant protein-a, and cytokines in vaginal fluid. Am J Reprod Immunol. 2012;68(3):244–50.PubMedPubMedCentralCrossRef

26.

Makinde J, Jones C, Bartolf A, Sibeko S, Baden S, Cosgrove C, et al. Localized cyclical variations in immunoproteins in the female genital tract and the implications on the design and assessment of mucosal infection and therapies. Am J Reprod Immunol. 2018;79(2):1–9.

27.

Patel MV, Ghosh M, Fahey JV, Ochsenbauer C, Rossoll RM, Wira CR. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions. Am J Reprod Immunol. 2014;72(1):22–33.PubMedPubMedCentralCrossRef

28.

Rahman S, Rabbani R, Wachihi C, Kimani J, Plummer FA, Ball TB, et al. Mucosal serpin A1 and A3 levels in HIV highly exposed sero-negative women are affected by the menstrual cycle and hormonal contraceptives but are independent of epidemiological confounders. Am J Reprod Immunol. 2013;69(1):64–72.PubMedCrossRef

29.

Rodriguez-Garcia M, Barr FD, Crist SG, Fahey JV, Wira CR. Phenotype and susceptibility to HIV infection of CD4+ Th17 cells in the human female reproductive tract. Mucosal Immunol. 2014;7(6):1375–85.PubMedPubMedCentralCrossRef

30.

Shrier LA, Bowman FP, Lin M, Crowley-Nowick PA. Mucosal immunity of the adolescent female genital tract. J Adolesc Health. 2003;32(3):183–6.PubMedCrossRef

31.

Shust GF, Cho S, Kim M, Madan RP, Guzman EM, Pollack M, et al. Female genital tract secretions inhibit herpes simplex virus infection: correlation with soluble mucosal immune mediators and impact of hormonal contraception. Am J Reprod Immunol. 2010;63(2):110–9.PubMedCrossRef

32.

Tawara F, Tamura N, Suganuma N, Kanayama N. Changes in cervical neutrophil elastase levels during the menstrual cycle. Reprod Med Biol. 2012;11(1):65–8.PubMedCrossRef

33.

Valore EV, Park CH, Igreti SL, Ganz T. Antimicrobial components of vaginal fluid. Am J Obstet Gynecol. 2002;187(3):561–8.PubMedCrossRef

34.

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.PubMedPubMedCentralCrossRef

35.

Stewart LA, Clarke M, Rovers M, Riley RD, Simmonds M, Stewart G, et al. Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement. JAMA. 2015;313(16):1657–65.PubMedCrossRef

36.

Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Chapter 4: Searching for and selecting studies. In: Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page M, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions version 6 (updated July 2019): Cochrane; 2019.

37.

Wallace BC, Small K, Brodley CE, Lau J, Trikalinos TA. Deploying an interactive machine learning system in an evidence-based practice center: abstrackr. Proceedings of the 2nd ACM SIGHIT International Health Informatics Symposium. Miami: Association for Computing Machinery; 2012. p. 819–24.

38.

Rohatgi A. WebPlotDigitizer 2019 [updated]; 2019. Available from: https://automeris.io/WebPlotDigitizer

39.

Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27(6):1785–805.PubMedCrossRef

40.

McGrath S, Zhao X, Steele R, Thombs BD, Benedetti A, Collaboration DESD. Estimating the sample mean and standard deviation from commonly reported quantiles in meta-analysis. Stat Methods Med Res. 2020;29(9):2520–37.

41.

Shi J, Luo D, Weng H, Zeng XT, Lin L, Chu H, et al. Optimally estimating the sample standard deviation from the fivenumber summary. Res Synth Methods. 2020;11(5):641–54.

42.

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.PubMedPubMedCentralCrossRef

43.

Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P, Stricker R. Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer. Clin Chem Lab Med. 2006;44(7):883–7.PubMedCrossRef

44.

Charbek E. Luteinizing Hormone: Medscape; 2015. Available from: https://emedicine.medscape.com/article/2089268-overview

45.

Leiva RA, Bouchard TP, Abdullah SH, Ecochard R. Urinary luteinizing hormone tests: which concentration threshold best predicts ovulation? Front Public Health. 2017;5:320.PubMedPubMedCentralCrossRef

46.

Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.PubMedPubMedCentralCrossRef

47.

Yuh T, Micheni M, Selke S, Oluoch L, Kiptinness C, Magaret A, et al. Sexually transmitted infections among Kenyan adolescent girls and young women with limited sexual experience. Front Public Health. 2020;8:303.PubMedPubMedCentralCrossRef

48.

Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, et al. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 2016;9(1):194–205.PubMedCrossRef

49.

Barousse MM, Theall KP, Van Der Pol B, Fortenberry JD, Orr DP, Fidel PL Jr. Susceptibility of middle adolescent females to sexually transmitted infections: impact of hormone contraception and sexual behaviors on vaginal immunity. Am J Reprod Immunol. 2007;58(2):159–68.PubMedCrossRef

50.

Fidel PL Jr, Barousse M, Lounev V, Espinosa T, Chesson RR, Dunlap K. Local immune responsiveness following intravaginal challenge with Candida antigen in adult women at different stages of the menstrual cycle. Med Mycol. 2003;41(2):97–109.PubMed

51.

Ghosh M, Shen Z, Fahey JV, Cu-Uvin S, Mayer K, Wira CR. Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract. Immunology. 2010;129(2):207–19.PubMedPubMedCentralCrossRef

52.

Hughes SM, Pandey U, Johnston C, Marrazzo J, Hladik F, Micks E. Impact of the menstrual cycle and ethinyl estradiol/etonogestrel contraceptive vaginal ring on granulysin and other mucosal immune mediators. Am J Reprod Immunol. 2021;86(2):e13412.PubMedPubMedCentralCrossRef

53.

Hwang LY, Scott ME, Ma Y, Moscicki AB. Higher levels of cervicovaginal inflammatory and regulatory cytokines and chemokines in healthy young women with immature cervical epithelium. J Reprod Immunol. 2011;88(1):66–71.PubMedCrossRef

54.

Jais M, Younes N, Chapman S, Cu-Uvin S, Ghosh M. Reduced Levels and Bioactivity of Endogenous Protease Cathepsin D in Genital Tract Secretions of Postmenopausal Women. AIDS Res Hum Retrovir. 2017;33(5):407–9.PubMedPubMedCentralCrossRef

55.

Lahey T, Ghosh M, Fahey JV, Shen Z, Mukura LR, Song Y, et al. Selective impact of HIV disease progression on the innate immune system in the human female reproductive tract. PLoS One. 2012;7(6):e38100.PubMedPubMedCentralCrossRef

56.

Lieberman JA, Moscicki AB, Sumerel JL, Ma Y, Scott ME. Determination of cytokine protein levels in cervical mucus samples from young women by a multiplex immunoassay method and assessment of correlates. Clin Vaccine Immunol. 2008;15(1):49–54.PubMedCrossRef

57.

Moscicki AB, Shi B, Huang H, Barnard E, Li H. Cervical-Vaginal Microbiome and Associated Cytokine Profiles in a Prospective Study of HPV 16 Acquisition, Persistence, and Clearance. Front Cell Infect Microbiol. 2020;10:569022.PubMedPubMedCentralCrossRef

58.

Novak RM, Donoval BA, Graham PJ, Boksa LA, Spear G, Hershow RC, et al. Cervicovaginal levels of lactoferrin, secretory leukocyte protease inhibitor, and RANTES and the effects of coexisting vaginoses in human immunodeficiency virus (HIV)-seronegative women with a high risk of heterosexual acquisition of HIV infection. Clin Vaccine Immunol. 2007;14(9):1102–7.PubMedPubMedCentralCrossRef

59.

Sriprasert I, Pakrashi T, Shah A, Jacot T, Bernick B, Mirkin S, et al. A pilot study: estradiol/progesterone effect on cervico-vaginal cytokines in premenopause and postmenopause. Climacteric. 2020;23(3):306–10.

60.

Thurman AR, Kimble T, Herold B, Mesquita PMM, Fichorova RN, Dawood HY, et al. Bacterial Vaginosis and Subclinical Markers of Genital Tract Inflammation and Mucosal Immunity. AIDS Res Hum Retrovir. 2015;31(11):1139–52.PubMedPubMedCentralCrossRef

61.

Thurman AR, Yousefieh N, Chandra N, Kimble T, Asin S, Rollenhagen C, et al. Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women. AIDS Res Hum Retrovir. 2017;33(8):807–19.PubMedPubMedCentralCrossRef

62.

Yegorov S, Joag V, Galiwango RM, Good SV, Mpendo J, Tannich E, et al. Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways. Nat Commun. 2019;10(1):2296.

63.

Safaeian M, Falk RT, Rodriguez AC, Hildesheim A, Kemp T, Williams M, et al. Factors associated with fluctuations in IgA and IgG levels at the cervix during the menstrual cycle. J Infect Dis. 2009;199(3):455–63.PubMedCrossRef

64.

Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol. 2015;7(5):1–19.

65.

Barbonetti A, Vassallo MR, Pelliccione F, D'Angeli A, Santucci R, Muciaccia B, et al. Beta-chemokine receptor CCR5 in human spermatozoa and its relationship with seminal parameters. Hum Reprod. 2009;24(12):2979–87.PubMedCrossRef

66.

Duan YG, Wehry UP, Buhren BA, Schrumpf H, Olah P, Bunemann E, et al. CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertilitydouble dagger. Biol Reprod. 2020;103(3):630–42.PubMedCrossRef

67.

Kutteh WH, Prince SJ, Hammond KR, Kutteh CC, Mestecky J. Variations in immunoglobulins and IgA subclasses of human uterine cervical secretions around the time of ovulation. Clin Exp Immunol. 1996;104(3):538–42.PubMedPubMedCentralCrossRef

68.

Usala SJ, Usala FO, Haciski R, Holt JA, Schumacher GF. IgG and IgA content of vaginal fluid during the menstrual cycle. J Reprod Med. 1989;34(4):292–4.PubMed

69.

Kutteh WH, Hatch KD, Blackwell RE, Mestecky J. Secretory immune system of the female reproductive tract: I. Immunoglobulin and secretory component-containing cells. Obstet Gynecol. 1988;71(1):56–60.PubMed

70.

Bergquist C, Johansson EL, Lagergard T, Holmgren J, Rudin A. Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina. Infect Immun. 1997;65(7):2676–84.PubMedPubMedCentralCrossRef

71.

Kozlowski PA, Williams SB, Lynch RM, Flanigan TP, Patterson RR, Cu-Uvin S, et al. Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: influence of the menstrual cycle. J Immunol. 2002;169(1):566–74.PubMedCrossRef

72.

Simpson SJ, Wiggins R, Fox JM, Mthethwa J, Cai C, Lacey CJN. Hepatitis B vaccination induces mucosal antibody responses in the female genital tract, indicating potential mechanisms of protection against infection. Sex Transm Dis. 2019;46(5):e53–e6.PubMedCrossRef

73.

Gaide Chevronnay HP, Selvais C, Emonard H, Galant C, Marbaix E, Henriet P. Regulation of matrix metalloproteinases activity studied in human endometrium as a paradigm of cyclic tissue breakdown and regeneration. Biochim Biophys Acta. 2012;1824(1):146–56.PubMedCrossRef

74.

Han JH, Kim MS, Lee MY, Kim TH, Lee MK, Kim HR, et al. Modulation of human beta-defensin-2 expression by 17beta-estradiol and progesterone in vaginal epithelial cells. Cytokine. 2010;49(2):209–14.PubMedCrossRef

75.

Patel MV, Fahey JV, Rossoll RM, Wira CR. Innate immunity in the vagina (part I): estradiol inhibits HBD2 and elafin secretion by human vaginal epithelial cells. Am J Reprod Immunol. 2013;69(5):463–74.PubMedCrossRef

76.

Archary D, Liebenberg LJ, Werner L, Tulsi S, Majola N, Naicker N, et al. Randomized cross-sectional study to compare HIV-1 specific antibody and cytokine concentrations in female genital secretions obtained by menstrual cup and cervicovaginal lavage. PLoS One. 2015;10(7):e0131906.PubMedPubMedCentralCrossRef

77.

Dezzutti CS, Hendrix CW, Marrazzo JM, Pan Z, Wang L, Louissaint N, et al. Performance of swabs, lavage, and diluents to quantify biomarkers of female genital tract soluble mucosal mediators. PLoS One. 2011;6(8):e23136.PubMedPubMedCentralCrossRef

78.

Fichorova RN, Richardson-Harman N, Alfano M, Belec L, Carbonneil C, Chen S, et al. Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study. Anal Chem. 2008;80(12):4741–51.PubMedPubMedCentralCrossRef

Title: Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data
Authors: 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
Raina Fichorova
Paul L. Fidel Jr
Keith R. Fowke
Suzanna C. Francis
Mimi Ghosh
Loris Y. Hwang
Mariel Jais
Vicky Jespers
Vineet Joag
Rupert Kaul
Jordan Kyongo
Timothy Lahey
Huiying Li
Julia Makinde
Lyle R. McKinnon
Anna-Barbara Moscicki
Richard M. Novak
Mickey V. Patel
Intira Sriprasert
Andrea R. Thurman
Sergey Yegorov
Nelly Rwamba Mugo
Alison C. Roxby
Elizabeth Micks
Florian Hladik
The Consortium for Assessing Immunity Across the Menstrual Cycle
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Cytokines
Progesterone
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-022-02532-9

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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