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One of the most-read articles we published in 2021 was about a Boston University professor who was leading one of five teams awarded $1.67 million in research funding from the National Institutes of Health to study whether COVID-19 vaccines impact menstruation. The story moved readers, and to date it has almost 500,000 page views, and 400 passionate comments from people sharing their personal experiences after being vaccinated.
Lauren Wise, a School of Public Health professor of epidemiology, is looking for evidence of COVID vaccines affecting periods through PRESTO (Pregnancy Study Online), an NIH-funded online study she runs. It follows women trying to conceive from preconception through six months after birth, and it’s been collecting data since 2013 on a range of aspects related to female health and fertility.
Four months after we first interviewed Wise about COVID vaccines and menstruation, we reconnected with her for an update on her research. Our conversation was recorded, so you can read along with the transcript, and hear personally from Wise about her work.
Both the recorded conversation and this transcript have been condensed and edited for clarity.
BU Today: How did researchers come to this idea of studying whether the COVID vaccines may be affecting menstruation?
Lauren Wise: I just want to say how surprised I was to see so many comments on The Brink about this topic. Maybe I shouldn’t have been so surprised ,but it’s pretty clear that menstruation is a really important health outcome for women and it’s great to see so many women talking about this. This is typically more of a taboo subject, but so many women have come out and expressed their experience about menstruation following vaccination and I’m glad that their voices are being heard. There have been a lot of anecdotal reports, on various social media outlets, where women have said after vaccination they’ve experienced changes in their menstruation, such as heavier menses, earlier onset of menses, or more painful periods. But in the clinical trials that came out looking at the effects of vaccination, they really just looked at life or death type outcomes and not reproductive outcomes like menstruation or fertility or even pregnancy outcomes. So, this is a very understudied area of investigation and I’m really happy that the National Institutes of Health has decided to fund these additional studies, looking at the extent to which COVID vaccination has an impact on menstruation.
To study the effects of the COVID vaccine on women’s menstrual cycle, which data have you been tracking?
I guess scientifically, thinking about why this could be happening, I mean, I think any agent that triggers an immune response could plausibly influence cellular processes in the uterus and ovaries that could have an impact on menstruation. Whether the effect might be short term or long term, or whether the effect is evident when we compare women who didn’t have any changes in their menses, we need to make sure that we study them, as well. And in addition to asking them about their lifestyle, their behaviors, their diet, a range of different exposures, we also ask them about their menstruation. And we also invite them to use a menstrual charting app, where they can track lots of information about their menstrual characteristics. And so, and in addition to that, we were able to add new questions on COVID vaccination and also COVID infection. And also stressors related to the COVID pandemic, which could plausibly confound these associations. And so we’ll be able to look at the COVID vaccination and changes in menstruation during six cycles of follow up, using multiple sources of data.
So, we have self-reported questionnaire data, and then we have the menstrual charting data. And some of the outcomes that we’re actually interested in that have also come up in some of the anecdotal reports are changes in cycle regularity, cycle length, intensity of menstrual flow, women have reported heavier periods. Length or duration of the menstrual flow like longer periods. And some women have actually reported bleeding between periods, so intermenstrual bleeding, and then there’s pain associated with menses. And we have information on vaccine type. So, the brand we can look at, and as I mentioned earlier, we can control for lots of additional factors that could explain why. Some women are having these symptoms versus not, so there’s some reports about perimenopausal women having more symptoms. COVID infection itself and then just the sheer number of COVID related stressors, like financial insecurity, childcare problems, [a] range of different stressors. And then of course we know that those who received the vaccination earlier tended to have preexisting health conditions, so we need to control for that. And, finally, occupation is another important consideration.
Since 2013, you have studied female health and fertility through the PRESTO study. Can you tell us a bit about it?
Sure, happy to talk about PRESTO [which stands for Pregnancy Study Online]. So, PRESTO is a prospective cohort study and we recruit women in the quick inspection states that they are actively trying to conceive, but they are not pregnant yet. So the goal really is to identify a group of women who have just recently continued birth control, so they are not using any condoms or any kind of contraception and they are trying to conceive. We do advertise primarily on social media, so it’s very much an internet-based study, where all the recruitment occurs through the internet. So, we might put an ad on Instagram or Facebook or Twitter and prospective participants will see the ad, they’ll click on the ad, they’ll go to the Boston University website, and they can read more about the study.
And then they can fill out the consent form if they’re interested, and then go right to the baseline questionnaire once we confirm their email address. So there’s this very innovative, efficient way of recruiting participants. And then getting them to fill out this pretty lengthy baseline questionnaire that really asks about, like medical history, contraceptive reproductive histories, just a range of different behaviors, lifestyle factors, diet, use of multivitamins, exercise. And then what we do, is we follow the women forward in time, using shorter questionnaires. So, every two months they fill out a shorter questionnaire asking whether they’ve conceived or not. And just updating any exposure information that could plausibly change over time. So, that’s why it’s so much shorter and so important to keep the participants engaged and connected to the study. And so they get followed up to 12 months or until they conceive, whichever comes first. And then they can also fill out an early pregnancy questionnaire and a late pregnancy questionnaire if they conceive, and then postpartum questionnaire six months after delivery.
What’s nice about PRESTO is right after they are the participants they are offered a premium menstrual charting app. And so they can enter information about days of their menstrual cycle, characteristics of the menstrual cycle, but also their fertility signs, so did they test for ovulation, did they look at the cervical, the consistency of their cervical mucus, did they check for their basal body temperature? All of these things can be helpful for identifying the fertile window and helping couples time intercourse to the fertile window and increase their chances of conception.
So, the reason why this cohort was so conducive to doing a study of vaccination and menstruation is that we have the menstrual charting app information. We also have all the menstrual characteristics from the baseline questionnaire and from follow up. And these women are not on hormones, I mean, it’s really key. One of the things that they put in the request for applications from the NIH was that the participants not be using hormones. And because all of these women are trying to conceive, none of them are on hormones, so it seemed like a really good fit.
Can you talk about how you incorporated studying whether COVID vaccination affected menstruation into the PRESTO study?
So, the study is ongoing, we are still actively recruiting participants from the United States and Canada, from all 50 states, from all 10 provinces, no restrictions. And we now have more than 16,000 women who have enrolled since 2013. And we recruit about 3,000 women per year in a good year. And, of course, provided we have funding from the NIH, which we are lucky to have. And we also recruit their male partners but to a much smaller extent. So, we have, I want to say nearly 4,000 male partners enrolled. And so the study really has not changed its focus. This menstruation project is very much like a supplemental side focus.
And I have to say we’ve received a lot of emails from people who are interested in the menstrual study that we’re doing, but very few of them have enrolled, very few of them are actively trying to conceive. So, we don’t think there’s gonna be a very large probability that women will enroll in the study because they’ve been having menstrual problems and they want to be able to contribute to the study. In fact, we’ve had to turn a lot of people away who wanted to enroll. That being said, the perspective design is really helpful, because what we do is we only compare women before and after they received the vaccination. So, it’s not like we’re enrolling people who have already had a vaccination and the menstrual changes into our study. We would only be looking at their data comparing before the vaccination versus after. And so that’s a good way to guard against any bias in the reporting of the menstrual factors or the selection of the participants into the study.
Because the study is ongoing, we will have the potential to look at the effects of the booster shots. So, today, we just added some questions about the booster shots—we had to allow for participants to report a change in the brand. So, we didn’t assume that they have the same type of vaccination—for example, Pfizer, you could switch over to Moderna and vice versa. So, we didn’t make that assumption. And we also collect a lot of information on the male partner because we know that, for example, fever that might be associated with vaccination could have a profound effect on semen quality. So, we tried to get a full range of information from both partners, and perhaps in the future, we could look at the effects of the booster on menstruation and also fertility.
Is it too soon to know if COVID vaccination affects menstruation?
We don’t know yet whether vaccination does have an effect on menstruation. So, I think we need to wait and see what the results of these studies come out with. And let’s just say there is an effect, we don’t know if it’s just a short-term effect or a longer-term effect. And so even if we see evidence of short-term effects, it may be that these effects go away and are no longer clinically meaningful or wreaking havoc on women’s lives over the long term, meaning like six months after vaccination. We also need to keep in mind what are the other types of reproductive outcomes of interest like fertility. That being said, I can tell you that I was surprised to see how low the percent vaccinated in our cohort was.
One area of concern women have raised is whether the COVID-19 vaccine can affect fertility. What are you seeing so far?
I think in particular young reproductive-aged women may be less likely to be getting vaccination against COVID because there’s so little known about the effects on their fertility. I think that’s a really major reason for vaccine hesitancy in this population. And for good reason, that maybe there’s not enough research out there on these effects. I think we find about 60 percent of the women reported vaccination and again this increases with time. And we only have gone through follow-up through early November, but still, I think some women are holding out. So, women are concerned about the anecdotal reports of effects of menstruation and some women are concerned about effects on fertility. We need to hear that, validate the concerns, and provide more data that we can use to evaluate the effects of vaccines on health outcomes.
Now that being said, I’ve been vaccinated, everybody on my team has been vaccinated. The Centers for Disease Control and Prevention recommends that all individuals aged five and above get vaccinated. And there’s no evidence that the vaccine has any impact on menstruation, fertility, any of these reproductive outcomes.
Fertility is definitely on our minds because that’s like our main outcome variable for this study. And I can tell you that we have completed our analyses of fertility and we have a manuscript that’s currently under review.
What about women who might be thinking about pregnancy loss and vaccination?
So, it is not as alarming as one would think—pregnancy loss is actually pretty common. It’s about 20 percent of all confirmed pregnancies. So, all pregnancies that might be confirmed by a home pregnancy test, about 20 percent of them do result in a loss after that point. So, it’s much more common than scientists initially conceived. And there have been two studies that have come out at least showing no effect of COVID vaccination on miscarriage. The data have been pretty limited. They’ve been looking at later losses because they’ve been using claims databases. Some of them actually might rely on self reported data. I don’t know if you’ve heard of the v-safe. So, it’s basically when I got my vaccination I actually got invited to participate. It’s like this link that was sent to me and I just filled it out based on how I was feeling, what are my symptoms. And I’d get a questionnaire through my text messages, I think it was like every week after I was first vaccinated, and then it was like every month thereafter. That is a sort of national dataset of individuals who did opt in to complete the questionnaires after they were vaccinated. And that study also did not find any association between COVID vaccination and miscarriage.
So, given all that, do you recommend women trying to conceive get vaccinated?
There’s a wealth of information that COVID infection itself has a really negative impact, a harmful impact on pregnancy outcomes and birth outcomes. And so taking into account all the available information right now, from all the data out there, I think the evidence is still weighing for vaccination. And so, it’s tough being a researcher in this area, because while we recognize the lack of data, as trained as an epidemiologist, we are strongly encouraging our participants to get vaccinated. So again, given the biology, what we know about how these vaccines could affect reproductive health given the available evidence. And there has been one study on fertility outcomes, a very small study that came out last month. And then all that data on the negative effects of COVID infection on pregnancy and birth outcomes. We strongly encourage women to get vaccinated against COVID.
Needless to say, COVID has caused a lot of stress in people’s lives, and in particular women, research has shown. Is it possible that’s causing menstruation changes?
There’s a lot more research out there on the effects of chronic stress and fertility. I don’t know as much about menstruation, but there’s certainly a link between the hypothalamic-pituitary-adrenal axis that produces stress hormones and the hypothalamic-pituitary-ovarian axis that produces ovarian hormones that are important for menstruation. So, there is quite a bit of literature on the connectedness, the interrelatedness between those two axes. And so, for sure in PRESTO and many previous studies, we have found that higher levels of perceived stress, as measured by the perceived stress scale, have been associated with reduced fertility. And that makes a lot of sense. So, certainly a part of the association we’re seeing here, or the anecdotal reports that we’re seeing when we look at vaccination and menstruation, could be driven by increased levels of stress related to the COVID pandemic. So, it’ll be very important to control for that. And, yes, I would say the evidence to support that is much clearer. Stress can harm reproduction, stress is negatively associated with menstruation.
So, has the study begun? And is there any progress you can talk about?
Yes, we have started cleaning the data and taking a look at the distribution of some of the variables that we’re interested in, like the menstrual characteristics. Part of the challenge is trying to identify the precise timing of the vaccination relative to each menstrual cycle. So, we’ve been doing a lot of additional coding and cleaning of the data. And so just looking at the first and second doses of Pfizer, Moderna, and the J&J dose, the first dose, we should be able to produce some results by spring 2022. And be able to look at those short-term and long-term effects over a six-month period. And then if there’s any interest in looking at the effects of the booster—which you’ve probably heard that the CDC is recommending that all adults get their booster shots at this point, not just specific subgroups who are at high risk. So, all adults are now being encouraged to get a booster. We would anticipate that as the prevalence of that increases, we will be able to start looking at the effects of the booster administration. Maybe by the summertime we should have some results there or next fall. So, the key thing is to be able to look not only at short-term effects, but also long-term effects, to see if these vaccination effects, if they do exist, if they linger or go away.
What can you say about results at this time?
I cannot give the actual results at this time. But I can tell you that we’ve already received comments back, so we’re in the process of revising the manuscript. And it really should be out within the next two months, maybe even sooner if everything goes well. And so, we will have some really good data, probably the best data out there on the extent to which COVID vaccination affects fertility. Because again, we really want to be able to study couples who are actively trying to conceive before they conceive and look at the effect of the vaccination on dependability in a prospective design. I can tell you that there’s no evidence currently that COVID vaccination has any negative impact on menstruation, fertility, pregnancy outcomes, birth outcomes. So, there’s no evidence to support any of those associations. And so I think based on the best available evidence right now, it makes good sense for women to get the COVID vaccination. Particularly because there is much better evidence that COVID infection adversely affects the risk of crazy outcomes, birth outcomes, many, many different outcomes, including morbidity, mortality. So, that’s where we’re at right now. I think I could make an even stronger statement in the future once this fertility paper comes out. Science is one of those things that just keeps evolving, right? There’s more and more information that comes out over time, especially with this pandemic. So, as we get more and more data about vaccination and its impact on menstruation, fertility, miscarriage, and other outcomes, I’ll be able to revise my statement.
I agree that it’s frightening. There’s so little that’s known. We need to validate the feelings that people have, their fears about vaccination. But I can tell you that millions of people have been vaccinated and they’re doing just fine. And again, there’s very little reason to think that the vaccine would be harmful to menstruation, fertility, or any of these other outcomes.
I imagine you are excited about seeing results and being able to share them, now that you have seen the overwhelming response to the study you are conducting.
So, I feel, obviously, very lucky to be in this space. And it’s a tremendous opportunity to learn so much more about these understudied health outcomes. And I feel so thankful and grateful to our participants for being willing to share this information with us. I don’t think these outcomes are particularly easy to share. I think they’re very sensitive, especially pregnancy loss, especially changes in menstruation. And so, I’m often in awe of the participants who are willing to enroll and share their experiences with us. So, yes, just a tremendous amount of gratitude that we are able to do this research. These couples are doing this out of the goodness of their hearts for altruistic reasons. And it really is such an amazing thing that they’re hoping to advance science. They’re hoping to help other couples, future couples, learn more about how to improve their fertility and how to reduce miscarriage and reduce adverse pregnancy outcomes. So, yes, I love my work. I love being in the space. It just feels fun, and eye-opening, and rewarding.
Can you briefly talk about who is involved in this research with you?
I just feel like I owe a lot of credit to our wonderful research team and also to Boston University for supporting our research way before we even got funding from the National Institutes of Health. We would apply for seed grants through BU. And we have so many students now at various levels of training in master’s degree program, doctoral program, postdoctoral fellows, who are actively engaged in the research and just contributing so much to collecting the data, analyzing the data, summarizing the data, disseminating the data. And really, it’s a team effort. It takes a village to do this kind of work. And I just really appreciate all their contributions, as well. So, I just want to make sure I give credit to Dr. Amelia Wesselink, who has been taking the lead on this analysis of COVID vaccination [and] menstruation. She’s also the first author of the paper on COVID vaccination and fertility that’s under review. There’s a brand new doctoral student, Sharonda Lovett, who is doing the analyses on the menstruation data. And these are really complicated analyses. So, I just wanna give her a lot of credit. And also Tanran Wang, who is our senior data analyst, who has just carefully processed the data and made them available to the team in a way that was conducive to getting their results generated and getting the results out there. So, it definitely takes a village. And we are very committed to getting these results out there for women who are really concerned about vaccination, and menstruation, and fertility, and miscarriage. And I certainly feel a tremendous sense of responsibility to get the most accurate data out there in a timely fashion.