Inflammatory mechanisms of menstrual cycle changes following COVID-19 vaccination in adolescents

Changes in menstrual cycle characteristics following COVID-19 vaccination have been reported in women and adolescent girls, yet the biological mechanisms underlying these changes remain poorly understood. Inflammation, though frequently hypothesized as a possible mechanism underlying this finding, has yet to be explicitly studied. Thus, the present study examined the relationships of ovarian hormones and inflammatory processes pre- and post-COVID-19 booster vaccination to menstrual changes among adolescent girls.

47 adolescent girls aged 13-20 who received a COVID-19 booster vaccination provided saliva samples and completed self-reported measures at five time points across the menstrual cycle. Saliva samples were assayed for inflammatory markers IL-1β, IL-6, TNF-α and ovarian hormones estradiol (E2) and progesterone.

Higher levels of IL-1β, measured 24 h post-vaccination, were significantly associated with shorter cycle length in the cycle during which the booster was administered. No significant effects were found for ovarian hormones or other inflammatory markers. Cluster analyses based on anti-spike immunoglobulin G (IgG) levels identified two distinct immune response profiles (high and low responders), though this was not significantly associated with menstrual cycle changes.

Pro-inflammatory cytokine IL-1β plays a significant role in explaining the shortening of the menstrual cycle following COVID-19 vaccination in adolescent girls, primarily impacting the cycle in which the vaccine was received This finding suggests that vaccine-induced inflammation can influence menstrual cycle regulation in adolescents, possibly due to the immaturity of the HPO-axes during adolescence.