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.

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.

Keywords: Chemokines; cytokines; immunology; inflammation; menstrual cycle.