Menstrual cycles are a somewhat forgotten vital sign of health – not unlike pulse, breathing rate and body temperature, but far less talked about.
Except in early 2021, when people started noticing that they had heavier than usual, or unexpected, menstrual bleeding after getting vaccinated against COVID-19.
Although these changes were short-lived, and most people's cycles returned to normal a month or two later, a question still lingered: how many vaccinated menstruators had experienced changes in their periods after vaccination?
Nearly half, according to a massive study published in Science Advances which surveyed more than 39,000 adults over three months, and found around 42 percent of those with regular menstrual cycles bled more heavily than usual after vaccination.
Most clinical trials focus on whether vaccines such as those made to combat COVID-19 are safe to give to someone who is pregnant (yes) or affect fertility (no). Vaccine trials also don't usually monitor participants for more than a week post-vaccination and rarely ask about menstruation.
Vaccine manufacturers, therefore, "had no way of addressing the extent to which this observation was a coincidence or a potential side effect of the vaccines," writes biological anthropologist and study author Katharine Lee of the Washington University School of Medicine and colleagues.
So, Lee joined forces with Kate Clancy, a human reproductive ecologist specializing in women's health at the University of Illinois at Urbana-Champaign, and started collecting data.
This was April 2021, and with multiple viral variants spreading in waves around the world, the researchers designed a web-based survey to capture a wide range of responses from menstruating adults.
"The response was overwhelming," Clancy told ScienceAlert in an email.
The idea that vaccines, which prime the immune system to defend against infections, could alter menstrual cycles is certainly not new.
In 1913, a study noted how the typhoid vaccine was associated with menstrual irregularities, which include missed, late, early and heavy periods. Hepatitis B and cervical cancer vaccines (against human papillomavirus or HPV) have also been known to disrupt menstrual cycles in some people.
"Generally, changes to menstrual bleeding are not uncommon or dangerous, yet attention to these experiences is necessary to build trust in medicine," Lee and colleagues explain.
The survey asked fully vaccinated people who had not had COVID-19 to report changes they had noticed in their period flow, cycle length, bleeding duration, and common menstrual symptoms after vaccination.
"Unexpected and unplanned menstrual changes can cause concern, distress, or other negative responses, in addition to discomfort and physical pain," Lee and colleagues write.
Of respondents who described their menstrual cycles as predominantly regular, nearly half of respondents in the online survey (42 percent) said they had heavier menstrual bleeding after getting vaccinated against COVID-19.
Roughly the same proportion of people (44 percent) reported no change to their period flow after vaccination.
A much smaller proportion of people had lighter periods.
What's more, a sizeable fraction of people who don't typically menstruate (because they are post-menopausal or use long-acting reversible contraceptives or gender-affirming hormones) also reported breakthrough bleeding.
Lee, Clancy, and colleagues caution that the survey results may not generalize to wider populations, and likely overestimate the prevalence of short-lived, heavy bleeding after vaccination.
"The point of this was never to perfectly assess prevalence," Clancy told ScienceAlert, but "to listen to people and validate their concerns because there were so many who were quick to dismiss them."
Clancy also reports that many survey respondents said they were "still very glad to have gotten the vaccine but that they were angry that no one had studied this beforehand".
The researchers stress that the findings are not indicative of changes to fertility and suggest that their study warrants further research into possible causes of temporarily disrupted cycles.
Among the people under 45 years old, those who experienced heavier periods after getting vaccinated were more likely to be older, identify as Latino or Hispanic, or have pre-existing conditions such as endometriosis.
We also know a host of biological stressors can unsettle even the most regular of menstrual cycles. High levels of sustained, intense exercise and calorie restriction, prolonged stress and inflammation can all disrupt or halt menstrual cycles without affecting fertility in the long run.
The wide-ranging experiences of survey respondents make it challenging to precisely define how period length, timing and flow may change after getting vaccinated.
Based on their data, Lee and Clancy have a hunch, though, about what might be happening.
They think it's more likely that vaccines could be messing with the body's inflammatory pathways, rather than changing ovarian hormone pathways because there was little difference between people with periods who were taking hormone contraception and those who weren't.
Of course, the only way to disentangle these possibly interwoven effects is to collect the data – and better it be from the outset, as part of clinical trials.
"One important lesson is that the effects of medical interventions on menstruation should not be an afterthought in future research," Victoria Male, a reproductive immunologist at the Imperial College London wrote in 2021 in the British Medical Journal.
"Clinical trials provide the ideal setting in which to differentiate between menstrual changes caused by interventions from those that occur anyway, but participants are unlikely to report changes to periods unless specifically asked."
Lee and Clancy's next steps are to reanalyze the full dataset from the first survey, to see if the findings hold true in a larger sample and over time. In a second study, they are also taking a look back at people's past experiences of healthcare.
"We hope we can better understand how healthcare experiences affect vaccine sentiments, to improve trust and communication and give patients the listening and the caring treatment they deserve," Clancy told ScienceAlert.
The study was published in Science Advances.