The link between COVID-19 vaccines and the menstrual cycle is one that has been hotly debated over the past couple of years. There are many reasons, with some (say, the inherent subjectivity and variability of period symptoms regardless of vaccine status) being arguably more legitimate than others (for example, the failure of vaccine companies to even ask about period changes during clinical trials). In a new Perspective for Science Magazine, reproductive immunologist Victoria Male has summarized the situation so far – and where the picture might go from here.

The COVID-19 pandemic is, believe it or not, only about three years old at this point – and working vaccines against the virus are even younger, with the first one in the entire world only being administered in December 2020. 

The speed of this development and rollout was the result of a massive worldwide drive to, you know, stop millions of people dying – and it worked very well. However, it did mean that identifying some potential side effects from the vaccines was effectively crowd-sourced to the public, with programs such as the UK’s Yellow Card scheme or bodies such as the FDA and CDC in the US logging reported post-shot symptoms – no matter how absurd or unrelated they happened to be.

Despite these reporting systems, one side effect became known more by word-of-mouth than any official channel – changes to the menstrual cycle. Hundreds of thousands of people across the world – including those who wouldn’t normally have a period any more, like transgender or post-menopausal people – found their shot in the arm came with a free side of extremely heavy bleeding, a longer-than-expected cycle, and many other weird and annoying effects to their monthly bleed.

Not only that, but the side effect appeared absent from official advice – leading many of those with first-hand experience of the symptom to grow frustrated with what they saw as the medical establishment’s continued bias against female health issues.

“More than half of the world’s population menstruate at some time in their lives, yet data about effects on menstruation are rarely collected in vaccine trials,” writes Male. “This must change – not least to offer reassurance that this area of public health is also taken seriously by vaccine developers.”

A handful of more recent studies have sought to close this gap in the knowledge. It’s now confirmed, for instance, that a COVID-19 vaccine can cause changes to the menstrual cycle – albeit small ones, rarely lasting more than two cycles. But the damage was done: misinformation had been unleashed, with various memes falsely claiming that the vaccine could interfere with your fertility, cause miscarriages, or any number of other grisly reproductive outcomes.

That made things dangerous. “Vaccines only work if people take them,” Male points out. “Although there is extensive evidence that COVID-19 vaccination does not affect fertility, misinformation that it could has been a major source of vaccine hesitancy among young women.”

Even now, the underlying mechanism for these menstrual changes is not fully understood, she notes – and while further information is clearly needed, it’s also challenging to collect. “Approaches using menstrual cycle tracking apps have proved powerful because large volumes of data are available and data collection in real time mitigates recall and recruitment bias,” Male explains, but “app users are not representative of the global population because they live mainly in high-income countries and young, white, educated individuals are overrepresented.” 

Then there’s the so-called “nocebo” effect – how do you separate the side effects caused by a vaccine from those caused by the knowledge that a person just had a vaccine? This has already proved a problem for COVID-19 vaccine researchers, but it’s perhaps even more significant with something like period length and strength, which are already highly variable from month to month. 

Nevertheless, Male sees cause for optimism. Research may have stumbled at the beginning with regard to period changes, but we now have the opportunity to make up for lost ground – researchers can recruit people in advance to study the effects of vaccination on their menstrual cycle, she suggests, and perhaps even open the door to wider questions about the link between the immune system and the menstrual cycle.

There are, undoubtedly, “important lessons to be learned,” Male writes – but, she concludes, “there is an opportunity, finally, to start making real progress in an area that has historically been understudied.”