Why Reports Of Menstrual Changes After COVID Vaccine Are Tough To Study

Sore arms. Headaches. Low-grade fevers.

These are some of the expected side effects of a COVID-19 vaccine — a sign that the body's mounting an immune response and learning how to fend off the coronavirus.

But thousands of people in the U.S. think they may have had other side effects that drugmakers and doctors never warned them about: unexpected changes in their menstrual cycles. Though many researchers and gynecologists say a causal link hasn't yet been established between the vaccines and the reported changes, it hasn't stopped the worry among some people. And so far, scientists haven't collected much data on whether or how the vaccines might affect a menstrual period.

Kate Clancy, a human reproductive ecologist and associate professor of anthropology at the University of Illinois Urbana-Champaign, and biological anthropologist Katharine Lee of Washington University School of Medicine in St. Louis hope to change that. Clancy has centered her research for decades around uterine function, ovarian hormones and menstrual cycles, and Lee is also a data engineer; her current postdoctoral work includes "collaborations on physical activity and reproductive hormones across the lifespan in healthy adult premenopausal women."

The two researchers have collected more than 140,000 reports from people who say they've noticed a change in their periods after vaccination; Lee and Clancy are formally documenting those cases in an open-ended study.

Clancy's interest was first piqued by her own experience.

"My period after dose one was one of the heaviest I remember having ever in my life," she says.

She took to social media with her story, and five months later, people are still responding to her original tweet.

"I did not anticipate it blowing up to the extent that it has," Clancy says. "A lot of emails, a lot of Instagram DMs and a lot of tweets of people who are just baring their souls to us."

The individual stories, even in large numbers, are not enough to prove vaccines are causing changes to menstruation. A healthy menstrual cycle is a complex hormonal process that can vary widely from person to person and month to month and is affected by many factors. Stress can contribute to lighter or heavier periods, for example, as can medication, a recent switch to a different form of birth control, or some herbal supplements.

Both the Food and Drug Administration and all three manufacturers of U.S.-approved vaccines tell NPR that they have not seen evidence that the COVID-19 vaccine is causing menstrual irregularities — let alone causing any health problems related to menstruation or fertility. The American College of Obstetricians and Gynecologists says it is aware of the reports, but that vaccination is highly recommended and that there is no reason to schedule vaccination around periods or other menstrual events.

"Obstetrician-gynecologists and other women's health care practitioners should lead by example by being vaccinated and encouraging eligible patients to be vaccinated as well," the association says.

Nonetheless, the outpouring of interest and concern among people who menstruate points to a blind spot in the way that clinical research on the COVID-19 vaccines was done. As with many other vaccine trials, the early COVID-19 studies did not ask much about reproductive health aside from questions around pregnancy. "It seeds doubt," Lee says. "It makes people feel like their bodies were not considered in part of the [clinical] trial."

The Centers for Disease Control and Prevention is giving the issue a closer look. A CDC spokesperson tells NPR that the agency is reviewing reports from one of its databases, called the Vaccine Safety Datalink, to see whether it's possible to detect how the vaccine may affect menstruation.

Any changes to menstrual cycle seem to be short-lived

The stories collected by Lee and Clancy usually describe only brief disruptions to menstruation. "From what we have seen so far, it appears that the changes to the menstrual cycle seem to be short-lived, just a couple of cycles," Lee says.

After vaccination, many people in the survey have reported heavy flows or bleeding at an unexpected time in the menstrual cycle, what's known as breakthrough bleeding or spotting.

This is what Lee went through after getting her first shot: spotting and cramping, "which for me is really, really unusual," she says. "I'm on the Mirena IUD so I normally don't experience a period."

Lee says it wasn't particularly serious, but that the cramps were uncomfortable. Many people who have contacted the researchers for their survey reported similar changes, but others had different experiences.

"We started hearing a lot about breakthrough bleeding, from people on long-acting reversible contraception, people on gender-affirming hormones, and postmenopausal people who were years and years out from their last period, sometimes decades out," Lee says.

Both researchers describe themselves as "pro-vaccine," especially given the dangers of COVID-19. Still they're troubled by the reports they've collected that some people are having their concerns dismissed out of hand by doctors. That's the sort of dismissiveness that can seed mistrust, Lee and Clancy note, and it's happening in part, they believe, because changes to menstruation are not officially listed as a possible side effect.

Rumors of menstruation problems have also fed larger conspiracy theories, and Lee says that further undermines the vaccines' credibility in some circles. "It seeds distrust, because it's not expected," she says.

Even if the disruption to the menstrual cycle is minor and transient, people taking the vaccine have a right to know if it might temporarily alter their cycle, so research determining that once and for all should be done, says Alice Lu-Culligan, an MD-Ph.D. candidate who studies immunology and reproductive health at Yale University: "That's a very simple question that they deserve to have an answer to," she says. "But at this time we really don't have an understanding of those changes."

An overlooked side effect is not the same thing as a cause for concern

The multitude of stories represents just a small fraction of the many tens of millions of people who have been vaccinated against COVID-19. Most have not experienced changes to menstruation, including women in the clinical trials, according to statements to NPR from Pfizer, Moderna and Johnson & Johnson.

"We haven't really heard much concern about menstrual issues," says Dr. Kathryn Edwards, a professor at Vanderbilt University School of Medicine who sits on an independent data monitoring committee for the Pfizer COVID-19 vaccine and is paid by the company for that work.

Edwards says the clinical trials would have picked up any issues that were truly dangerous. For example, researchers were able to detect an extremely rare and dangerous side effect, known as "thrombosis with thrombocytopenia syndrome," that sometimes caused incidental changes to menstruation. "If it were leading to hospitalizations and severe illness, we would capture that," she says.

But she acknowledges that relatively minor or unusually rare changes to menstruation might be missed. Participants in the clinical trials are handed a checklist asking about minor side effects such as headaches or arm soreness, but Edwards says there aren't any specific questions such as, "Are your menstrual periods irregular? Is your flow heavier?"

Because this data isn't collected, trial participants are left to report changes to menstruation as "adverse events'' — a situation that could cause the trials to miss relatively minor disruptions, she said.

Lee, one of the anthropologists studying the effect of the vaccines on menstruation, says she doesn't think she would personally describe her breakthrough bleeding as an "adverse event."

New research does suggest there's at least a plausible route by which vaccines could alter menstruation. Yale's Lu-Culligan says that recent studies show immune cells play a role in both building up and breaking down the uterine lining during a cycle.

"When you're altering your immunological state with a vaccine, it's certainly possible that you could be altering a bit of the normal dynamics you could have," she says.

Why such research is difficult to design

But proving whether or not it's possible the vaccine could cause a minor menstrual disruption is difficult because periods can be so variable from person to person and cycle to cycle, says Dr. Laura Riley, chair of obstetrics and gynecology at New York-Presbyterian/Weill Cornell Medical Center in New York City.

"The menstrual cycle itself is just so incredibly difficult to study, because there are so many other things that may impact it," Riley says.

Factors such as stress or minor illness can change the duration of a period or the amount of bleeding, and some people have irregular cycles all the time. Moreover, what constitutes a "heavy" period varies from person to person and is highly subjective. "Just even thinking about how you would design that study to me is mind-boggling," Riley says.

Edwards says the COVID-19 vaccine posed an especially difficult challenge for drugmakers. As the companies hurried to test the vaccines last year, safety monitors were focusing all their energy on spotting truly dangerous side effects. "I want people to understand that we're not blowing them off," Edwards says, "but we have some priorities that we have to have."

The CDC says exploratory work to look into the issue is now underway, although the agency did not offer a timeline for when, or even if, a full study could be conducted.

But even if the question can't be answered for COVID-19 vaccines, Riley says she believes issues such as the effects on menstruation need to be addressed in future clinical trials of drugs and vaccines: "Because when you can't answer those questions, you're asking people just to believe."

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