Where You Are in Your Menstrual Cycle Could Alter Vaccine Response
COVID-19 vaccination during the follicular phase was associated with greater side-effect reporting in a new study.
Following the COVID-19 pandemic, it became apparent that some women experienced changes in their menstrual cycles after vaccination.
A handful of studies explored how vaccination impacts the menstrual cycle. Now an international collaboration led by the London School of Hygiene & Tropical Medicine has turned this question on its head, asking whether menstrual cycle phases alter vaccination outcomes. The findings, published in Nature, suggest that menstrual cycle phase at vaccination may influence side effect profiles and protection against infection.
The menstrual cycle: An overlooked biological clock
Many factors influence vaccine-induced immunity and outcomes, including underlying health conditions, environmental factors, genetics, and gender. Poppy Cooper, lead study author, elaborated: “We've known for a long time that reproductive hormones affect immunity and that they drive sex differences in vaccine response. Those same hormones change across the menstrual cycle, so the logical question is: could where someone is in their cycle affect how they respond to a vaccine?”
Previous work has shown that females have higher vaccine reactogenicity: they are more likely to experience side effects and may produce more antibodies than their male counterparts, but this doesn’t necessarily translate into greater vaccine efficacy.
Typically, vaccine research focuses on target groups, such as elderly individuals at risk of the flu or people living in regions with a higher risk of infectious diseases. Within these efforts, the circadian rhythm has been studied in chrono-optimization investigations that assess how treatments can be adjusted to match the body’s daily rhythm. Yet another biological clock has remained understudied—the menstrual cycle.
Cooper explained the relevance: “The follicular and luteal phases are the two broad phases of the cycle, each dominated by a different ovarian hormone.”
“Immune cells—neutrophils, dendritic cells, macrophages, T cells, and B cells—all carry receptors for these hormones,” she continued. “This makes the two phases a natural, if simplified, proxy for comparing the hormones' effects and a biologically meaningful starting point for statistical analysis.”
The menstrual cycle, put simply
In the follicular phase, estrogen is the dominant hormone, as it supports egg maturation. In the luteal phase, progesterone predominates, which would support implantation if an egg is fertilized after ovulation. If fertilization and implantation do not occur, the cycle starts over. The menstrual period marks the end of the luteal phase, when the uterine lining sheds, and re-entry into the follicular phase.
Follicular-phase vaccination linked to higher side-effect reporting
Between late 2021 and early 2022, the team invited women to participate in a survey through the period-tracking app, Clue. The survey covered COVID-19 vaccination outcomes, demographic data, lifestyle factors, and health markers.
Of the respondents, 1474 had tracked sufficient cycle data for matching and were included in the analysis, which aimed to answer two key hypotheses:
- Vaccine reactogenicity will be greater when vaccination occurs during the follicular phase.
- Post-vaccination COVID-19 infection risk will be lower when vaccination occurs during the follicular phase.
Cooper explained the rationale: “Broadly, estrogen tends to promote immune response, while progesterone tends to dampen it.”
“In the follicular phase, when estrogen is rising, we might expect someone to be more likely to report side effects, reflecting this stronger immune response, which might also translate into a more robust antibody response,” she continued.
Using survey responses and period-tracking data, participants were classified as vaccinated in either the follicular or luteal phase. In addition to effectively “splitting” the cycle into two phases, the team explored the ebb and flow of side-effect reporting across cycles by mapping them onto a standardized timeline.
“As expected, side effects didn't switch on and off neatly at the phase boundaries: reporting climbed through the late follicular phase, dropped sharply just after ovulation, then climbed again to a second peak in the late luteal phase, possibly reflecting premenstrual symptoms,” Cooper explained.
“Overall, though, side effect reporting was more likely following vaccination in the follicular phase than the luteal phase.” — Poppy Cooper, PhD researcher and lead study author
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The study found that women vaccinated during the follicular phase had 35% higher odds of reporting at least one side effect compared with those vaccinated during the luteal phase. Regarding infection risk, although direct comparison suggested that follicular-phase vaccination was associated with longer time-to-infection, the study lacked sufficient infection events to draw a definitive conclusion.
A starting point for menstrual phase vaccination research
Cooper highlighted the need to interpret these findings with caution: “Our study shouldn't be read as evidence that anyone should time their vaccine around their cycle. We can't be sure of the mechanism underlying our findings. Are people in the follicular phase mounting a genuinely stronger immune response, or are they simply more sensitive to the aches and fatigue that follow a jab?”
“Estrogen and progesterone both influence immunity and pain perception. Future studies need to tease these potential mechanisms apart,” she added.
Further studies would benefit from quantitative analysis to confirm hormone levels and immune response, particularly given that the standardized timeline used doesn’t account for menstrual variation between individuals.
Both a benefit and a limitation of the study is reliance on self-reported data. On the one hand, the prospective nature of cycle tracking provides more accurate cycle-phase assessment and prevents hindsight bias from influencing participant-reported outcomes.
At the same time, the survey was completed on average ~8 months after vaccination, which introduces recall bias, especially given that COVID-19 vaccines were widely discussed in the media. Additionally, Cooper added: “Symptoms attributed to the vaccine could have been coincidental menstrual symptoms; sensitivity analyses excluding people vaccinated right around their period still held, though it remains a possibility.
“What this study does establish is that the menstrual cycle isn't just ‘noise’ to control for in immunology research. It's a meaningful biological variable that deserves proper study. Women's biology has too often been excluded from research design rather than investigated on its own terms, so even asking the question properly is a step forward, regardless of where the answer eventually lands,” concluded Cooper.
Reference: Cooper PA, Boniface ER, Darney BG, et al. Menstrual cycle phase and its association with COVID-19 vaccine outcomes among period tracking app users. npj Womens Health. 2026. doi: 10.1038/s44294-026-00150-x
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