Menstrual cycle phase and its association with COVID-19 vaccine outcomes among period tracking app users

Despite known hormonal influences on immune function, the impact of menstrual cycle phase on vaccine outcomes remains unexplored. Using prospectively tracked cycle data from the Clue period tracking-app, matched with an in-app survey of 1474 women, we compared self-reported COVID-19 vaccine outcomes between follicular-phase (estrogen-dominant) and luteal-phase (progesterone-dominant) vaccinated women. Side effect presence, severity and number were analysed using binary, ordinal, and negative binomial regression respectively, and post-vaccination time to infection (67–372 days) via Wilcoxon rank-sum test. Follicular-phase vaccination was associated with 35% higher odds of any self-reported side effects (OR: 1.35, 98.3% CI: 1.01–1.79) compared to luteal-phase vaccination. Median time to infection was 35 days longer following follicular-phase vaccination (200 [140–237] vs 165 [107–210] days, p = 0.05), though infection numbers were limited. These findings suggest menstrual cycle phase warrants consideration in sex-based immunity research and may inform future research on vaccination and personalised health strategies.