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

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-alpha (IFN-alpha), and RANTES (regulated upon activation normal T-cell expressed and secreted) levels varied significantly across the menstrual cycle. The proinflammatory factors IL-1 beta, IL-6, IL-8, and HGF were 1.5-3 times higher during menses than the late follicular phase. In marginal structural models, IL-1 beta, 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. (C) 2014 by American Society for Reproductive Medicine.