Clue data study links follicular-phase vaccination to more side effects

A study using menstrual tracking data from the Clue app has found that people vaccinated against COVID-19 during the follicular phase of their cycle were 35% more likely to report vaccine side effects than those vaccinated during the luteal phase. The research, published in npj Women's Health, is among the first to examine whether cycle timing affects vaccine response, and its authors say the findings support a broader call to incorporate menstrual cycle data into mainstream immunology research.

The study was led by Poppy Cooper at the London School of Hygiene and Tropical Medicine and Alexandra Alvergne at the University of Montpellier, in collaboration with researchers from Oregon Health and Science University and Clue itself. Of the 1,474 Clue users included in the analysis, 760 had been vaccinated during the follicular phase and 714 during the luteal phase. Crucially, cycle phase was determined by matching survey responses against each participant's own previously tracked cycle data, rather than relying on self-reported estimates.

Key findings and caveats

The 35% higher odds of reporting any side effect during the follicular phase held up across multiple sensitivity analyses, including after excluding participants vaccinated around menstruation, which the researchers say rules out a simple confound with premenstrual or menstrual symptoms. There was no evidence, however, that follicular-phase vaccination was associated with more severe side effects or a greater number of them.

A secondary finding showed that participants vaccinated during the follicular phase went a median of 35 days longer before a subsequent COVID-19 infection (200 days versus 164 days). The researchers are explicit that this result is exploratory and hypothesis-generating: only 82 infections were recorded across the whole sample, far too few to support a clinical recommendation.

Amanda Shea, fractional Chief Science Officer at Clue, said: "To truly understand women's health, we need to stop treating the menstrual cycle as background noise and start recognising it as a fundamental part of human biology."

The research team is equally explicit that the findings should not prompt people to time their vaccinations around their cycle. Receiving a dose when one is available remains the priority.

Market and research context

The study sits within a growing field of women's health research that has historically been underfunded relative to its disease burden. Femtech, the technology category that includes cycle-tracking apps, fertility tools and menopause platforms, has attracted increasing venture interest over the past several years, though it remains a small fraction of overall digital health investment.

Clue, operated by Berlin-based BioWink GmbH, says it holds data on more than 250 million tracked cycles and over 30 billion data points from consenting users, making it one of the larger longitudinal menstrual health datasets available to researchers. The company has existing research partnerships with MIT, Oxford, Columbia and UC Berkeley. Its scale gives it a meaningful advantage in powering observational studies of this kind, though observational designs carry inherent limitations around causality that this study's authors acknowledge.

The biological rationale is reasonably well established: oestrogen is generally associated with heightened immune activity, while progesterone tends to dampen immune responses. Prior research has shown women mount stronger antibody responses than men to several vaccines, including influenza, MMR and hepatitis, and report more side effects on average. This study extends that literature by asking whether those differences vary systematically across the cycle itself.

For the immunology and women's health research communities, the study's primary value may lie less in its specific numerical findings and more in its methodological demonstration: that large-scale, passively collected cycle-tracking data can be matched against health outcomes to answer questions that traditional trial designs have rarely asked.