title: Association of inflammation markers with menstrual symptom severity and premenstrual syndrome in young women.
abstract: OBJECTIVE
  Are markers of chronic inflammation associated with menstrual symptom severity and premenstrual syndrome (PMS)?
  
  
  CONCLUSIONS
  Serum levels of inflammatory markers, including interleukin (IL)-2, IL-4, IL-10, IL-12 and interferon (IFN)-γ were positively associated with menstrual symptom severity and/or PMS in young women.
  
  
  BACKGROUND
  Chronic inflammation has been implicated in the etiology of depression and other disorders that share common features with PMS, but whether inflammation contributes to menstrual symptom severity and PMS is unknown.
  
  
  METHODS
  Cross-sectional study of 277 women aged 18-30 years, conducted in 2006-2011.
  
  
  METHODS
  Participants provided information on menstrual symptoms, lifestyle, diet, anthropometry and other factors by questionnaire and/or direct measurement, and a mid-luteal phase fasting blood sample was taken between 7 a.m. and 12 p.m. Total, physical and affective menstrual symptom scores were calculated for all participants, of whom 13% (n = 37) met criteria for moderate-to-severe PMS and 24% (n = 67) met PMS control criteria. Inflammatory factors assayed in serum included IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α, granulocyte macrophage colony stimulating factor, IFN-γ and C-reactive protein.
  
  
  RESULTS
  After adjustment for age, smoking status and BMI, total menstrual symptom score was positively associated with levels of IL-2 (percentage difference in women at the 75th percentile of total symptom score versus at the 25th percentile = 24.7%; P = 0.04), IL-4 (21.5%; P = 0.04), IL-10 (28.0%; P < 0.01) and IL-12 (42.0%; P = 0.02) in analyses including all participants. Affective menstrual symptom score was linearly related to levels of IL-2 (percentage difference at 75th percentile versus 25th percentile = 31.0%; P = 0.02), while physical/behavioral symptom score was linearly related to levels of IL-4 (19.1%; P = 0.03) and IL-12 (33.2%; P = 0.03). Additionally, mean levels of several factors were significantly higher in women meeting PMS criteria compared with women meeting control criteria, including IL-4 (92% higher in cases versus controls; P = 0.01); IL-10 (87%; P = 0.03); IL-12 (170%; P = 0.04) and IFN-γ (158%; P = 0.01).
  
  
  CONCLUSIONS
  Our study has several limitations. While a single blood sample may not perfectly capture long-term levels of inflammation, ample data suggest that levels of cytokines are stable over time. Although we did not base our assessment of PMS on prospective symptom diaries, we used validated criteria to define PMS cases and controls, and excluded women with evidence of comorbid mood disorders. Furthermore, because of the cross-sectional design of the study, the temporal relation of inflammatory factors and menstrual symptoms is unclear.
  
  
  CONCLUSIONS
  To our knowledge, this is among the first studies to suggest that inflammatory factors may be elevated in women experiencing menstrual symptoms and PMS. Additional studies are needed to determine whether inflammation plays an etiologic role in PMS.
  
  
  BACKGROUND
  This study was funded by the Departments of Public Health and Nutrition and by a Faculty Research Grant, University of Massachusetts Amherst. No conflicts declared.
  
  
  BACKGROUND
  N/A.
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003-9304, USA ebertone@schoolph.umass.edu.
authors.forename: E R
authors.initials: ER
authors.lastname: Bertone-Johnson
authors.affiliation: Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts, 100 Holdsworth Way, Amherst, MA 01003, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Ronnenberg
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003-9304, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Houghton
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003-9304, USA.
authors.forename: C
authors.initials: C
authors.lastname: Nobles
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003-9304, USA Behavioral Medicine Research Division, Department of Psychiatry, Baystate Medical Center, 259 Chestnut Street, Springfield, MA 01199, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Zagarins
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003-9304, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Takashima-Uebelhoer
authors.affiliation: Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts, 100 Holdsworth Way, Amherst, MA 01003, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Faraj
authors.affiliation: Division of Biostatistics and Epidemiology, Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003-9304, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Whitcomb
mesh_terms: D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D016014:Linear Models; D011293:Premenstrual Syndrome / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; C508594:IL2 protein, human; C508598:IL4 protein, human; D007376:Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: cytokines; inflammation; menstrual cycle; premenstrual syndrome