Menstrual Cycle Changes Associated With COVID-19 Vaccine
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A new study published in Science Advances outlines the most comprehensive data on the effects of COVID-19 vaccines on menstrual cycles to date.
Reported menstrual cycle changes post-COVID-19 vaccination
Clinical trials are structured to explore the effectiveness and safety of a new investigational medicinal product (IMP), such as a vaccine. As part of an IMP’s safety evaluation, any potential side effects that occur after administration are evaluated. It is acknowledged that experiencing some side effects post-vaccination is a common phenomenon and is generally not a cause for concern. The 2020 trials of the first COVID-19 vaccines – which progressed to receive authorization for human use – reported that some participants experienced tenderness, pain, warmth, itching or bruising at the injection site, in addition to some tiredness, chills, joint pain and nausea.
Fast forward to the present day and ~12.16 billion doses of a COVID-19 vaccine have been administered globally, with 66% of the world’s population receiving at least one dose. Such large-scale administration of the vaccines is enabling the collection of safety and efficacy data in real-time, including the reporting of side effects that were not investigated in the clinical trials.
The 2020 COVID-19 vaccine clinical trials did not explore whether COVID-19 vaccines have any side effects on the menstrual cycle. This is not a rare case; clinical research has been criticized for a lack of inclusivity, with the “complexities of the menstrual cycle” even being cited as a basis to exclude certain individuals from research studies.
In early 2021, reports of menstrual cycle changes post-COVID-19 vaccination began to emerge across formal 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 start collecting data on these reports.
“Dr. Lee and I had our own wonky period experiences post-vaccine,” says Clancy. “If Dr. Lee hadn’t pointed them out to me first, I may never have made the connection myself. After I tweeted about it and the response was overwhelming, we designed a survey instrument that would allow us to capture these experiences as well as any factors that might make one more at risk of this side effect. 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 colleagues used their survey to ask individuals about their experiences after receiving a COVID-19 vaccination. “We recruited online, mostly through Twitter but also Facebook and Instagram. The survey really took off in what is called ‘snowball sampling’, where people who participated often encouraged others to participate. The media attention we got also led a lot of people to our study. Because the language of our study was gender inclusive a lot of LGBT+ people also shared our study and encouraged people to participate,” Clancy describes.
On June 29, 2021, the research team downloaded their data and started their analysis. To avoid confounding the data, individuals that had received a diagnosis of COVID-19 – known to be associated with menstrual cycle changes – and those aged 45–55 years – who could be considered perimenopausal – were excluded. In total, results from 39,129 participants were analyzed (this comprised 35,572 individuals that identified as women, and 3,557 gender-diverse individuals).
“Our recruitment efforts were aimed at getting anyone with a uterus (or formerly with a uterus) who was over 18 and had been vaccinated, but it is likely there is some selection bias where people who experienced symptoms were more likely to participate,” – Clancy.
All respondents had received two doses of a COVID-19 vaccine at least 14 days prior to completing the study, including the Pfizer, Moderna, AstraZeneca, Johnson & Johnson Novavax and other vaccines.
“We focused our analysis on those who regularly menstruate and those who do not currently menstruate but have in the past,” said Clancy. “The latter group included postmenopausal individuals and those on hormonal therapies that suppress menstruation, for whom bleeding is especially surprising.”
Changes to menstrual flow identified
The survey results identified that 42.1% of menstruating individuals had experienced a heavier menstrual flow following vaccination, with some reporting that this occurred within the first 7 days, while others experienced changes 8–14 days afterwards. In contrast, 43.6% of respondents reported that they did not experience any changes to their menstrual flow.
“Our key finding is that increased bleeding (heavier among menstruating people, and breakthrough bleeding among non-menstruating people) is real, mechanistically plausible and experienced by a significant number of people,” says Clancy. “It is also now supported by several prospective studies that have also found the same thing.”
“A secondary finding is that there are key factors that increase the chance someone may have this increased bleeding phenotype – being older (for menstruating people – younger if postmenopausal), having been pregnant/had kids, having a hyperproliferative reproductive condition.”
Why could these changes be occurring?
The exact biological mechanism behind menstrual cycle changes experienced post-vaccination has not yet been pinpointed, but there are several hypotheses cited in the study. Vaccines induce an immune response, generating the production of antibodies. This induced immune response can lead to changes in hemostasis and inflammatory pathways in the body. It’s possible that such effects can impact 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 is going to have all sorts of downstream effects, including on the uterus,” says Clancy. “The endometrium (lining of the uterus) is needing to bleed and clot appropriately as it repairs and heals. A disruption of immune function or inflammation is going to disrupt those processes in at least some people.”
The researchers hypothesized that individuals more vulnerable to such disruption would be those who had uteruses that had undergone considerable cycles of repairing and healing, for example: people who had many periods (i.e., were older), had been pregnant or had children, or participants that 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 COVID-19 vaccines can adversely impact fertility.
"The important message is 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 both male and female fertility and pregnancy. The evidence shows that getting the vaccine has no negative impact on any of these things and it is important for protecting pregnant women and their infants. These new findings are of no surprise and certainly no reason to delay or avoid a COVID-19 vaccine," says Associate Professor Helen Petousis-Harris, a vaccinologist at the University of Auckland, 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. Causality between COVID-19 vaccination and menstrual cycle changes therefore cannot be proven – a limitation the researchers acknowledge. However, the team emphasize that the data is useful to “help shape the narrative around the nature of short-term menstrual changes, help clinicians working with vaccine-hesitant patients, and develop the necessary, on-the-ground data on this new phenomenon”.
The study also points to the need for clinical trials to enquire about menstrual cycle experiences. “At minimum, trials should include questions about menstrual periods and the daily adverse reporting should extend to at least 14 days because many of our respondents got their heavy periods outside of the 7-day window common in most trial designs,” says Clancy. “We had some participants tell us that they were involved in vaccine trials and that they tried to report their symptoms – in one case the person they talked to dismissed their concerns and said ‘you just must be perimenopausal’ rather than writing down their symptoms.”
Advancing research into menstrual cycle changes post-vaccination
Drs Clancy and Lee are excited to further advance their research. “First, we want to re-analyze the full dataset to see if our findings from the first few months of data collection are still supported,” Clancy says. “Then we want to analyze a second survey that we sent out to our participants that looks at how many periods were disrupted, among those who experienced changes.”
The second survey explores the stressors that could worsen symptoms, including lifestyle factors such as stress. “It looks at the kinds of healthcare experiences people had in the past,” says Clancy. “So many people shared with us experiences of institutional betrayal in healthcare settings – times when they were dismissed or mistreated when they tried to say they had menstrual changes or heavy bleeding with the vaccine – we wanted to explore that more and give more people a chance to get to share what happened,” she concludes.
Any changes to menstrual cycles – be it temporary or long-term – can be distressing to an individual and may prompt concerns regarding their health status. To that end, the research team encourage anyone experiencing breakthrough bleeding to consult with their physician.
Dr. Kathryn Clancy was speaking to Molly Campbell, Senior Science Writer for Technology Networks.
Reference: Lee K, Junkins E, Luo C et al. Investigating trends in those who experience menstrual bleeding changes after SARS-CoV-2 vaccination. Sci Adv. 2022. doi: 10.1126/sciadv.abm7201.