Reported changes in menstrual cycle after vaccination for COVID-19
Clinical trials are structured to investigate the efficacy and safety of a new investigational medicinal product (IMP), such as a vaccine. As part of the safety evaluation of an IMP, any adverse effects that occur after administration are evaluated. It is recognized that the occurrence of some adverse reactions after vaccination is common and generally not a cause for concern. The 2020 trials of the first vaccines for COVID-19 – which went ahead and received approval for human use – reported that some participants experienced tenderness, pain, warmth, itching or bruising at the injection site, in addition to some fatigue, chills, pain in the joints and nausea. Fast forward to today and ~12.16 billion doses of COVID-19 vaccine have been administered globally, with 66% of the global population receiving at least one dose. Such large-scale administration of the vaccines allows the collection of safety and efficacy data in real time, including the reporting of adverse events not investigated in clinical trials. 2020 COVID-19 vaccine clinical trials not investigate whether the COVID-19 vaccines have side effects on the menstrual cycle. This is not a rare case. Clinical research has been criticized for its lack of inclusion, with “complications of the menstrual cycle” even being cited as a basis for excluding some people from research studies. In early 2021, reports of menstrual cycle changes following the COVID-19 vaccination began to appear in official channels, including the UK’s yellow card scheme and social media. This prompted researchers such as Dr. Kathryn Clancy, professor of anthropology at the University of Illinois Urbana-Champaign, and Dr. Katharine Lee, professor of anthropology at Tulane University, to begin collecting data for these reports. “Dr. Lee and I have had our own uncomfortable post-vaccination experiences,” says Clancy. “If Dr. Lee hadn’t pointed them out to me first, I might never have made the connection myself. After I tweeted about it and the response was overwhelming, we designed a survey tool that would allow us to record these experiences as well as any factors that could put this side effect at risk. We really wanted to listen to people and validate their concerns because there were so many who were quick to dismiss them.”
Conducting the survey
Clancy and his colleagues used their survey to ask people about their experiences after being vaccinated against COVID-19. “We recruited online, mainly through Twitter but also Facebook and Instagram. The survey really took off in what’s called “snowball sampling,” where people who participated often encouraged others to participate. The media attention we received also led many people to our study. Because the language of our study was gender inclusive, many LGBT+ people also shared our study and encouraged people to participate,” Clancy describes.
On June 29, 2021, the research team downloaded their data and began their analysis. To avoid confounding the data, people who had received a diagnosis of COVID-19 – known to be associated with menstrual cycle changes – and people aged 45–55 years – who could be considered perimenopausal – were excluded. In total, results from 39,129 participants were analyzed (these included 35,572 people who identified as female and 3,557 people of different race).
“Our recruitment efforts aimed to get anyone with a uterus (or formerly with a uterus) who was over 18 years of age and had been vaccinated, but it is possible that there was some selection bias where people who developed symptoms were more likely to participate.” , – Clancy.
All respondents had received two doses of a COVID-19 vaccine at least 14 days before completing the study, including Pfizer, Moderna, AstraZeneca, Johnson & Johnson Novavax, and other vaccines.
“We focused our analysis on those who menstruate regularly and those who do not currently menstruate but have in the past,” Clancy said. “The latter group included postmenopausal people and people on hormonal treatments that suppress menstruation, for whom bleeding is especially surprising.”
Changes in menstrual flow were detected
The survey results found that 42.1% of menstruating subjects experienced heavier periods after vaccination, with some reporting that this happened within the first 7 days, while others experienced changes 8-14 days later. In contrast, 43.6% of respondents reported that they experienced no change in their periods. “Our key finding is that increased bleeding (heavier among menstruating women and heavier bleeding in non-menstruating men) is real, mechanistically plausible, and experienced by a significant number of people,” says Clancy. “Now it’s also supported by several prospective studies that have also found the same thing.” “A secondary finding is that there are key factors that increase the likelihood of someone having this increased bleeding phenotype – being older (for menstruating people – younger if postmenopausal), being pregnant/having children, having a hyperproliferative reproductive state.
Why might these changes be occurring?
The exact biological mechanism behind the menstrual cycle changes seen after vaccination has yet to be identified, but there are several hypotheses mentioned in the study. Vaccines trigger an immune response, creating the production of antibodies. This induced immune response can lead to changes in hemostasis and inflammatory pathways in the body. It is possible that such effects may influence the complex chemical interactions that regulate menstrual cycles. Other vaccines, such as the human papillomavirus (HPV) vaccine, have also been reported to have a temporary impact on menstrual cycles. “The uterus is an immune organ. When the immune system is activated by something like a vaccine, it will have all kinds of effects, including in the womb,” says Clancy. “The endometrium (lining of the uterus) needs to bleed and thicken properly as it repairs and heals. A disorder of immune function or inflammation is going to disrupt these processes in at least some people.” The researchers hypothesized that the people most vulnerable to such a disruption would be those with uteruses that had undergone significant cycles of repair and healing, for example: people who had many periods (i.e. were older), were pregnant or had children, or participants who they may have hyperproliferative disorders, such as endometriosis or fibroids. “These hypotheses were supported in our study,” notes Clancy.
COVID-19 vaccines and fertility
It is important to note that there is no evidence to suggest that COVID-19 vaccines can adversely affect fertility. “The important message is that it is very clear that the vaccine has no adverse effects on fertility or pregnancy. There are many studies that have looked at the effect of the vaccine on fertility and pregnancy in both men and women. The evidence shows that the getting the vaccine has no negative impact on any of these things and is important to protect pregnant women and their babies.These new findings are not surprising and there is certainly no reason to delay or avoid a vaccine for COVID-19 says Associate Professor Helen Petousis-Harris. , a vaccinologist at the University of Oakland, who was not involved in the study.
Changing the landscape of clinical research
The new study adopted a self-report methodology and is retrospective in nature. Therefore, causality between the COVID-19 vaccination and menstrual cycle changes cannot be proven – a limitation the researchers acknowledge. However, the team emphasizes that the data are useful to “help shape the narrative around the nature of short-term menstrual changes, assist clinicians working with vaccine-hesitant patients, and develop the necessary, on-the-ground data.” for this new phenomenon. “. The study also highlights the need for clinical trials to research menstrual cycle experiences. “At a minimum, trials should include questions about menstrual periods, and daily spam reporting should span at least 14 days, because many of our respondents had their heavy periods outside the 7-day window that is common in most test designs,” says Clancy. “We’ve had some participants tell us they were in vaccine trials and tried to report their symptoms – in one case the person they spoke to dismissed their concerns and said ‘you must just be in menopause’ instead of writing down their symptoms . “
Research advances in menstrual cycle changes after vaccination
Drs Clancy and Lee are excited to take their research further. “First, we want to reanalyze the full data set to see if our findings from the first months of data collection are still supported,” says Clancy. “Next, we want to analyze a second survey that we sent to our participants, which looks at how many periods were disrupted, among those who experienced change.”
The second research investigates stressors that could worsen symptoms, including lifestyle factors such as stress. “It looks at the kinds of health care experiences people have had in the past,” Clancy says. “So many people have shared with us experiences of institutional betrayal in health care settings – times they were fired or abused when they tried to say they had menstrual changes or heavy bleeding with the vaccine – we wanted to explore this further and give more people the opportunity to to share what happened,” he concludes.
Any changes in menstrual cycles – whether temporary or long-term – can be upsetting for a person and can cause health concerns…
