Menstrual cycle-associated changes in blood levels of interleukin-6, alpha 1 acid glycoprotein, and C-reactive protein

Based on previous studies we hypothesized that interleukin-6 (IL-6) plasma levels would increase during the menstrual cycle, in analogy to the increase in IL-1 levels seen during the luteal phase. Thus we have investigated menstrual cycle-associated changes in IL-6, alpha 1 acid glycoprotein (AGP), and C-reactive protein (CRP). The study design was cross-sectional and was conducted in 18 healthy premenopausal women with regular menstrual cycles and in 15 age-matched men. The women had blood drawings in the follicular phase, at midcycle, and in the luteal phase of the menstrual cycle. A single blood sample was obtained from men to compare IL-6 levels between sexes. The median IL-6 level was 0.68 pg/ml (95% confidence interval (CI): 0.60 to 1.05) in the follicular phase and did not change significantly during the menstrual cycle. IL-6 levels did not differ between women and men (0.79 pg/ml; CI: 0.66 to 1.05; p > 0.05). Median AGP levels decreased by 6% (CI: -14% to 1%) during the luteal phase (p = 0.005), and a significant correlation between mean AGP and IL-6 levels was found (r = 0.60; p = 0.01). Median CRP levels increased by 44% (CI: 27% to 59%; p < 0.001) at midcycle and by 31% (CI: 17% to 68%; p = 0.002) in the luteal phase, and there was a significant correlation between the relative increase in CRP at midcycle and the relative increase in progesterone levels during midcycle (r = 0.60; p = 0.01) and the luteal phase (r = 0.71; p = 0.001), In conclusion, we found no sustained menstrual cycle-dependent changes in systemic IL-6 plasma levels. AGP and CRP levels may be differentially regulated during the menstrual cycle of healthy women: AGP levels correlated with IL-6 levels, and AGP levels decreased during the menstrual cycle, whereas CRP levels increased during the menstrual cycle and correlated with the increase in progesterone levels. The reason for the observed changes in CRP levels remains to be elucidated.