Interleukin-6 is higher in naturally menstruating women compared with oral contraceptive pill users during the low-hormone phase

Abstract

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), vasoconstrictive substance, endothelin-1 (ET-1), and measures of vascular function among relatively lower and higher hormone phases of non-OCP and OCP. Concentrations of estrogen, progesterone, IL-6 and ET-1 and measures of vascular function were collected in 22 women (22±1 y, OCP: n=12) during the early follicular (EF, ≤5 days of menstruation onset) and early luteal (EL, 4±2 days post-ovulation) phases of non-OCP 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. Vascular function was assessed via brachial artery flow-mediated dilation (%FMD). Concentrations of endogenous estrogen and progesterone were higher in the EL phase as compared to 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 as compared to the EL phase as well as compared to 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 during the lower hormone phase, despite similarities in vascular function and concentrations of ET-1 between groups and phases.

Arterial stiffness and blood pressure are similar in naturally menstruating and oral contraceptive pill‐using women during the higher hormone phases

“…57.12 (29.10) vs. 53.0 (28.8) pg/ml; progesterone: 1.4 (1.0) vs. 1.2 (0.9) ng/ml), as previously reported (Eagan et al, 2021). Contrastingly, among non-OCP users, serum concentrations of oestrogen and progesterone were significantly lower in the EF phase as compared to the EL phase (oestrogen: 91.8 (34.5) vs. 120.9 (32.6) pg/ml; progesterone: 1.4 (0.6) vs. 5.1 (3.6) ng/ml) (Eagan et al, 2021).…”

“…Following haemodynamic and anthropometric measures, cardiovascular health and fitness were assessed with a cycle ergometer $${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$$ exercise test, as previously described (Eagan et al., 2021). Briefly, $${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$$ was determined using a graded exercise protocol lasting until participants met volitional fatigue or failed to maintain a cycling cadence of 75–80 rpm.…”

“…Following haemodynamic and anthropometric measures, cardiovascular health and fitness were assessed with a cycle ergometer VO 2 peak exercise test, as previously described (Eagan et al, 2021).…”

“…Upon arrival for Visits 2 and 3, blood was drawn from an antecubital vein into serum separator tubes, spun, pipetted and stored in samples as described in a previous manuscript (Eagan et al, 2021).…”

Similar inflammatory response and conduit artery vascular function between sexes following induced inflammation

“…Interestingly, in a recent study from our laboratory, baseline IL-6 concentrations were higher during the early follicular phase compared with the midluteal phase in premenopausal, naturally menstruating women. These findings support a partial withdrawal of oestrogen-related dampening effects on IL-6 production (Eagan et al, 2021). Although women have lower oestrogen concentrations during the early follicular phase compared with other phases of the menstrual cycle, it is plausible that oestrogen receptors in women have greater sensitivity compared with those of men, potentially explaining the similar, not higher, IL-6 concentrations in women compared with men.…”