Interleukin-6 Is Higher In Naturally Menstruating Women Compared With Oral Contraceptive Pill Users During The Low-Hormone Phase

Endogenous sex hormone concentrations vary between healthy naturally menstruating (non-OCP) and oral contraceptive pill-using (OCP) women, as well as across cycles. The aim of this study was to investigate potential differences in concentrations of inflammatory cytokine interleukin-6 (IL-6) and vasoconstrictive substance endothelin-1 (ET-1) and measures of vascular function among relatively lower- and higher-hormone phases of non-OCP and OCP women. Concentrations of estrogen, progesterone, IL-6, and ET-1 and measures of vascular function were collected in 22 women (22 +/- 1 yr, OCP: n = 12) during the early follicular (EF, <5 days of menstruation onset) and early luteal (EL, 4 +/- 2 days postovulation) phases of non-OCP subjects and were compared to the placebo pill (PP, <= 5 days of PP onset) and active pill (AP, <= 5 days of highest-dose AP) phases of OCP subjects. Vascular function was assessed via brachial artery flow-mediated dilation (%FMD). Concentrations of endogenous estrogen and progesterone were higher in the EL phase compared with the EF phase of non-OCP (P = 0.01) but were similar between phases of OCP (P > 0.05). IL-6 was higher in non-OCP during the EF phase compared with the EL phase (P = 0.03) as well as compared with OCP during the PP phase (P = 0.002) but was similar between groups during the EL and AP phases, respectively (P > 0.05). Concentrations of ET-1 and measures of %FMD were similar between groups and unaffected by phase (P > 0.05). Thus, there exists variation in inflammation between young, healthy non-OCP and OCP women during the lower-hormone phase, despite similarities in vascular function and concentrations of ET-1 between groups and phases.NEW & NOTEWORTHY We demonstrate that despite having similar macrovascular function and concentrations of the vasoconstrictive substance endothelin-1 (ET-1) healthy naturally menstruating women display higher concentrations of circulating IL-6 during the lower-hormone phase of their menstrual cycle compared with 1) the higher-hormone phase of their menstrual cycle and 2) the lower-hormone phase of healthy women using oral contraceptive pills.