Urinary cytokine and chemokine profiles across the menstrual cycle in healthy reproductive age women

Capsule:
Using longitudinal data on menstrual cycle function, we evaluated urinary cytokines levels for assessment of reproductive function by considering detection, variation across the menstrual cycle, and correlations with hormones.

Authors:
Brian W. Whitcomb, Ph.D., Sunni L. Mumford, Ph.D., Neil J. Perkins, Ph.D., Jean Wactawski-Wende, Ph.D., Elizabeth R. Bertone-Johnson, Sc.D., Kristine E. Lynch, Ph.D., Enrique F. Schisterman, Ph.D.

Volume 101, Issue 5, Pages 1383–1391.e2

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.

Design:
Longitudinal cohort study.

Setting:
Academic institution.

Patient(s):
Healthy, reproductive-aged women with self-reported regular menstrual cycles and at least one observed ovulatory cycle (n = 248).

Intervention(s):
None.

Main Outcome Measure(s):
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.

Result(s):
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.

Conclusion(s):
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.

  • fdominguez

    Congratulations to the authors. Great work¡ The high number of cycles
    and time points measured in this work made it very valuable. I wonder if you
    have planned similar studies trying to correlate urine cytokine levels with
    implantation/pregnancy rates and other parameters directly related to
    reproduction success.

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