Why We Need To Investigate Menstrual Changes After COVID-19 Vaccination

Across the globe, 5.86 billion doses of a COVID-19 vaccine have now been administered, and 29.91 million shots are given on a daily basis. The COVID-19 vaccines rollout has proven a crucial tool in our fight against the SARS-CoV-2 virus. We are starting to see life return to varying forms of "normal" as an increasing number of people are immunized in different regions of the world. Importantly, the more people that receive their vaccine, the more real-time data we are gathering on the side effects that the different authorized vaccines can have both common and rare.

One side effect that has been reported to the Yellow Card scheme – and that was not studied in the vaccine clinical trials – is changes to the menstrual cycle. Increasing calls for this phenomenon to be explored further led to the National Institutes of Health (NIH) dedicating $1.67 million of funding to this area of unmet need.

Victoria Male, lecturer in reproductive immunology at Imperial College London, recently published an editorial in the British Medical Journal addressing the "plausible link" between COVID-19 vaccines and menstrual cycle changes. In the piece, she wrote that a key lesson from the vaccine rollout is that the effects of medical interventions on menstruation should not be an afterthought in future research.

Technology Networks interviewed Dr. Male to learn more about the plausible link and what kind of research she would like to see in this space. Dr. Male also discussed why a lack of conversation surrounding menstruation may lead individuals to conceal information in this context.

Molly Campbell (MC): Why might an immune response, such as that which is triggered by vaccination, influence the menstrual cycle?

Victoria Male (VM): I should make it clear that we don’t know for sure that this is happening yet, but we can imagine at least two biologically plausible mechanisms. One is that a perturbation to the immune system, such as occurs after vaccination or infection, could affect sex hormones and that this in turn will affect the menstrual cycle. The other is that the immune cells that help control the build-up and break down of the lining of the uterus could be affected by the general activation of the immune response, and this could in turn affect the timing and heaviness of bleeding.

MC: There is no evidence that suggests that COVID-19 vaccines adversely impact fertility. Can you expand on some of this evidence?

VM: There are two situations in which we have compared pregnancy rates between vaccinated and unvaccinated people. One was in the clinical trials, in which accidental pregnancies occurred at the same rate in the vaccinated and unvaccinated groups. Following the general rollout of the vaccines, we also have comparisons of vaccinated and unvaccinated IVF patients – and again there’s no difference in pregnancy rate, or any measure of fertility.

MC: Vaccination against human papillomavirus (HPV) has been associated with menstrual changes. Can you talk more about these changes?

VM: One study looked at around 30,000 Japanese teenagers. In this group, those who had had the HPV vaccine were more likely to report heavy or irregular periods than those who had not. In this study, the participants knew whether they had received the vaccine or not – indeed, had chosen whether to receive it – so it is not as good evidence as we would get in a proper trial. But nonetheless, it is suggestive.

MC: Why is the way in which the Yellow Card data is collected making it difficult to form firm conclusions?

VM: At the time I wrote the article, there were 30,000 reports of changes to periods following vaccination to the Yellow Card reporting scheme, but what we really want to do is compare the rates at which people experience these changes following vaccination to the rates at which they would normally experience them and see if there is a difference. Yellow Card does not collect all the data we would need to calculate the rates even in people who are vaccinated, let alone those who are unvaccinated.

That’s not to say I think Yellow Card is a bad scheme by the way. It is very good at doing what it was designed to do – detecting severe adverse events that rarely happen in unvaccinated people.

MC: What impact might the reported changes have on vaccine hesitancy and how can we look to combat this?

VM: It is important to say that most people who have noticed a change find their period goes back to normal very quickly, and that research shows that there’s no impact of vaccination on fertility. These are the two main concerns that come up. But you can understand that people might be worried by this and that’s why I think it is important to do this research. Then, we will definitively be able to say either “no, there’s no difference” or “yes, this is a side effect like fever or fatigue that happens to X percent of people, so you shouldn’t worry if it happens to you”.

MC: What research would you like to see conducted into menstrual changes following COVID-19 vaccination?

VM: We really need approaches that measure the chance that you will have – say – a late period in any given cycle, and then compare that rate to the rate of late periods following vaccination. One way of doing this is to recruit people before they get their vaccine and ask them to track their cycles before and after vaccination. A higher-tech way is to take advantage of the data that exists already from menstrual cycle tracking apps – although the difficulty there is that you then have to add a function that allows people to log their vaccines to the app.

MC: You state that an important lesson here is that the effects of medical interventions on menstruation should not be an afterthought in medical research. Why do you think this has been an afterthought in this case?

VM: In the trials, information was solicited about events that were expected but not serious, such as fever and fatigue, or serious. Since changes to the menstrual cycle didn’t fit in either of these categories, it wasn’t solicited – and most people won’t volunteer information about their periods unless specifically asked. This is partly because we don’t talk about our periods as much as maybe we should. This lack of discussion not only means that people didn’t volunteer information, it also means that people designing trials don’t necessarily have this in the forefront of their minds.

Victoria Male was speaking to Molly Campbell, Science Writer for Technology Networks.