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Hum Reprod. 2014 Sep;29(9):1987-94. doi: 10.1093/humrep/deu170. Epub 2014 Jul 17.

Association of inflammation markers with menstrual symptom severity and premenstrual syndrome in young women.

Author information

1
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.
2
Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts, 100 Holdsworth Way, Amherst, MA 01003, USA.
3
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.
4
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.

Abstract

STUDY QUESTION:

Are markers of chronic inflammation associated with menstrual symptom severity and premenstrual syndrome (PMS)?

SUMMARY ANSWER:

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.

WHAT IS KNOWN ALREADY:

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.

STUDY DESIGN, SIZE, DURATION:

Cross-sectional study of 277 women aged 18-30 years, conducted in 2006-2011.

PARTICIPANTS/MATERIALS, SETTING, 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.

MAIN RESULTS AND THE ROLE OF CHANCE:

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).

LIMITATIONS, REASONS FOR CAUTION:

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.

WIDER IMPLICATIONS OF THE FINDINGS:

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.

STUDY FUNDING/COMPETING INTERESTS:

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.

TRIAL REGISTRATION NUMBER:

N/A.

KEYWORDS:

cytokines; inflammation; menstrual cycle; premenstrual syndrome

PMID:
25035435
DOI:
10.1093/humrep/deu170
[Indexed for MEDLINE]
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