Menstrual cycle timing may influence vaccine side effects, research suggests

Menstrual cycle timing may affect vaccine side effects, according to a study involving 1,474 users of period-tracking app, Clue.

People vaccinated before ovulation were more likely to report side effects than those vaccinated after ovulation.

They also appeared to go longer before a subsequent Covid-19 infection, although the researchers said this finding was exploratory.

Amanda Shea, fractional chief science officer at Clue, said: “We know that immune function fluctuates across the menstrual cycle, yet it’s still rarely considered in mainstream health research.

“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.

“Incorporating cycle data into research is essential to building the evidence needed for more personalised and effective care.”

In the study, participants vaccinated during the follicular phase had 35 per cent higher odds of reporting any vaccine side effect than those vaccinated during the luteal phase.

The follicular phase occurs before ovulation, when oestrogen is dominant. The luteal phase follows ovulation and is dominated by progesterone.

Sensitivity analyses produced similar findings after people vaccinated around menstruation were excluded, suggesting the association was not simply explained by menstrual or premenstrual symptoms.

A sensitivity analysis checks whether findings remain consistent when researchers change parts of their analysis.

The researchers found no evidence that vaccination during the follicular phase was linked to more severe side effects or a greater number of side effects.

Those vaccinated during the follicular phase went a median of 35 days longer before reporting a subsequent Covid-19 infection.

The median was 200 days among those vaccinated during the follicular phase, compared with 164 days for those vaccinated during the luteal phase.

However, only 82 infections were recorded across the sample.

The researchers said the result was exploratory and intended to generate a hypothesis rather than provide evidence that vaccination timing improves protection.

The study was led by Poppy Cooper at the London School of Hygiene & Tropical Medicine and Alexandra Alvergne at the University of Montpellier.

They worked with researchers from Oregon Health & Science University and cycle-tracking company Clue.

The findings add to growing evidence that reproductive hormones may influence immune function.

Oestrogen is generally associated with heightened immune activity, while progesterone tends to have a dampening effect.

Previous studies have found that women often develop stronger antibody responses than men after vaccines for influenza, measles, mumps and rubella, and hepatitis. They also often report more side effects.

Antibodies are proteins made by the immune system that identify and help fight infections.

Clue said research has been central to its work since the company was founded.

Its users have tracked more than 250m cycles and contributed more than 30bn data points with their consent, creating what the company describes as one of the world’s largest long-term menstrual health datasets.

Clue works with researchers at institutions including MIT, Oxford, Columbia and the University of California, Berkeley.

The company said the study was possible because users chose to contribute their tracked cycle data to research.

Rhiannon White, chief executive of Clue, said: “Every time the Clue community tracks their cycle, they’re helping answer a question about their own body that medicine has too often ignored.

“This study is a small example of something bigger: when women are given the tools to understand themselves, and the research catches up to meet them, real change becomes possible.”

Researchers surveyed Clue users about when they received their first Covid-19 vaccine dose, any side effects they experienced and subsequent infections.

The responses were matched with cycle information that each participant had previously recorded in the app, rather than relying on recalled estimates.

Of the 1,474 users included, 760 were vaccinated during the follicular phase and 714 during the luteal phase.

The researchers stressed that people should not use the findings to schedule vaccinations around their menstrual cycle.

They said receiving a vaccine when it is available remains far more important than the phase of the cycle in which it is given.

As the first study to investigate the association, further evidence is needed before any recommendations can be made.

The researchers said future vaccine and immunology studies should consider menstrual cycle phase as an important variable.