title: Urinary cytokine and chemokine profiles across the menstrual cycle in healthy reproductive-aged women.
abstract: OBJECTIVE
  To assess the utility of urinary cytokines for monitoring reproductive function by considering detection, variation across the menstrual cycle, and relations with hormones.
  
  
  METHODS
  Longitudinal cohort study.
  
  
  METHODS
  Academic institution.
  
  
  METHODS
  Healthy, reproductive-aged women with self-reported regular menstrual cycles and at least one observed ovulatory cycle (n = 248).
  
  
  METHODS
  None.
  
  
  METHODS
  Urinary cytokines measured by 30-plex immunoassays in 3,550 biospecimens, and nested random-effects analysis of variance (ANOVA) and marginal structural models used to evaluate variability and relations with hormones.
  
  
  RESULTS
  For 24 of 30 evaluated factors, detectable levels were observed in at least 50% of urine samples. Interleukin-6 (IL-6), IL-8, IL-10, IL-15, granulocyte colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interferon-α (IFN-α), and RANTES (regulated upon activation normal T-cell expressed and secreted) levels varied significantly across the menstrual cycle. The proinflammatory factors IL-1β, IL-6, IL-8, and HGF were 1.5-3 times higher during menses than the late follicular phase. In marginal structural models, IL-1β, IL-6, IL-8 were associated with lower estradiol and progesterone concentrations.
  
  
  CONCLUSIONS
  Variability during the menstrual cycle and correlations with reproductive hormone levels support a role of cytokines in the menstrual cycle; however, because of the limited variability for most cytokines considered, the utility of urine as a matrix for assessment of inflammation in menstrual cycle function appears limited for clinical purposes.
authors.affiliation: Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts. Electronic address: bwhitcomb@schoolph.umass.edu.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Whitcomb
authors.affiliation: Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Sunni L
authors.initials: SL
authors.lastname: Mumford
authors.affiliation: Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Perkins
authors.affiliation: Department of Social and Preventive Medicine, State University of New York, Buffalo, New York.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Bertone-Johnson
authors.affiliation: Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Lynch
authors.affiliation: Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Enrique F
authors.initials: EF
authors.lastname: Schisterman
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D018925:Chemokines / Q000652:urine*; D015331:Cohort Studies; D016207:Cytokines / Q000652:urine*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008597:Menstrual Cycle / Q000652:urine*; D008875:Middle Aged; D011446:Prospective Studies; D060728:Reproductive Health; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines
keywords: Chemokines; cytokines; immunology; inflammation; menstrual cycle