COVID Vaccine and Menstruation — need for more robust studies

 Victoria Male, PhD, of Imperial College London's Department of Metabolism, Digestion and Reproduction, highlights recent research on the effects of COVID-19 vaccination on menstruation.

The following is a transcript of her remarks:

We first started to think that there might be an impact of COVID vaccination on menstrual periods back in the spring of 2021.

Particularly in the U.K., we first vaccinated vulnerable people -- mostly elderly, too old to have periods. But as we started to vaccinate younger people, people started to say, "Oh, I feel like I noticed that the vaccine affected my period." Because periods vary naturally, and because we don't often talk about our periods, although maybe we should, it was really difficult to know if that variation that people were noticing was actually variation caused by the vaccines or if it was natural variation that they were just noticing because we'd started thinking about it and talking about it.

So in the United States of America and in Norway, some money was put aside to actually study this formally. In the United Kingdom, we had no money, but some of us had a go with very limited resources. The first sort of formal work on that came out in January of this year, 2022, but we now have really a lot of data. The best data comes from menstrual cycle tracking apps.

With respect to timing of periods, what those have shown is if we've got thousands -- about 20,000 people -- who are tracking their periods and get vaccinated, and we compare those to thousands of people who haven't been vaccinated, in the month that you get the vaccine on average, if you get one dose, your period's going to be half a day late. The people who really notice the difference are the people who get two doses in the same cycle, which some people will, particularly in countries that use a 3-week dose interval. Those people will notice about a 2.5- or a 3-day delay to their next period.

It's really important to say that even for the people who have this 2.5- or 3-day delay, their periods are back to normal within two cycles. Actually, most people's periods are back to normal; either they never stopped being normal, or they're back to normal the next cycle. So, that's timing.

Another thing that people noticed was they felt that their periods were heavier. This has been harder to study because people tend to log their menstrual flow less often in menstrual cycle tracking apps. But there is one app study which is now out in preprint, and that suggests that about 4% more people will notice a heavier-than-usual period if they're vaccinated.

There was another study that didn't use app data, that just asked people to retrospectively think about their periods, a Norwegian study, and that found that about 7% of people notice a heavier-than-usual period after vaccination.

Again, where these studies have followed up with people, they're back to normal. Actually for heaviness, they're back to normal the next month.

So, the headline finding is that there are changes, but they're really small compared to natural variation. They go back to normal very quickly.

In other studies that we've done looking at fertility, there's no effect of COVID vaccination on fertility, actually even the month you get vaccinated. There's one study that's looking at people, tracking them over the whole period of the pandemic, and it finds that if you're trying to get pregnant, you're just as likely to get pregnant in the month that you get vaccinated as in any other month.

So we have quite good evidence now that there is an effect, but what we don't have such good evidence about is why there's an effect. But, we do have some clues.

All COVID vaccines seem to have this effect. So, it's not like you can avoid it by getting a particular brand. In fact, there's some evidence that other vaccines have this effect as well. To me as an immunologist, that suggests that instead of there being a particular ingredient which is doing this, it's to do with the activation of the immune response, which happens with all vaccines -- that's what they're designed to do.

So then we start to think how could the immune response impact menstrual cycles, and actually we have a lot of crosstalk between the immune system and reproductive system. That's my whole job.

One of the things that we think could be going on here is that when we get vaccinated, we start off what's called an innate immune response, which later on kind of kicks off the protective part of the immune response. The innate immune response is the bit that to us as people is mostly annoying. It's the bit that gives you a sore arm and makes you feel a little bit under the weather. And I think it's probably the bit that is affecting periods.

So we get the production of the immune mediators, and I think it's probably going to be a particular class of the immune mediators called cytokines, that can crosstalk with the sex hormones that drive the menstrual cycles. This might be changing the timing of the cycle.

The evidence we have in support of this idea is that people who are on combined hormonal contraception, so we are giving them estrogen and progesterone -- those ovarian hormones -- separately on top of their own hormones, keeping them at a nice high, flat level for the contraception, but also that's quite useful for us scientifically. Those people are much less likely to notice a change to the timing of their periods. That gives us the suggestion that this is mediated by hormones.

Another thing that gives the suggestion that this is mediated by hormones is that when in your cycle you get vaccinated makes a difference to how likely it is that you're going to see a change to the timing of your period. We tend to think of the first half of the menstrual cycle as being a little bit more sensitive to perturbations. There's some evidence that if you get vaccinated in the first half of the menstrual cycle, that is what is associated with having a late period. If you get vaccinated in the second half of the menstrual cycle, which is a little bit more robust, those people tend not to see a late period. So, that's the evidence that timing might be affected by crosstalk between the immune system and hormones.

What might be the mechanism that causes us to have heavier periods? There, I think it's a lot less clear. There's one idea that the lining of the uterus is really, really rich in immune cells, and some of these immune cells are involved in the buildup and the breakdown of the uterine lining. Perhaps if we activate these or perturb these by vaccination, then that might have an effect on the buildup and the breakdown, which we would see as a heavier period.

The piece of evidence that supports this idea is quite a small one. Basically, you are more likely to experience a heavier-than-usual period post-vaccination if you're older. There's the idea that older people are a little bit less good at tissue repair -- it's sadly one of the things that happens as you get older -- so that's the suggestion, that vaccination might be contributing to heavier-than-usual periods via immune-mediated mechanisms of tissue repair in the lining of the uterus.

We actually had clues, for more than a century, perhaps, that stimulation of the immune response can cause changes to menstrual periods, but no one really thought to look into it. In some ways, I think that's a little bit indicative of the way that female reproductive health is often treated in medical research.

What's been really interesting about this is that if we'd understood this all along, this particular problem that came up where we noticed this effect, it made people worry really quite a lot. It made people hesitate, people who probably would have benefited from being vaccinated because, you know, COVID is not nice at all. So this tells us that actually sometimes if we're shortsighted and we don't think about female reproductive health, it can come out in all other aspects of healthcare.

So, I think it's important to look a little bit more about the female reproductive health, not just because it's a super important area in its own right, but also because it crosstalks into so many other areas of health. We'll find ourselves hitting ceilings in other areas of health if we don't take this particular aspect seriously.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/101908