COVID-19 Vaccination May Protect Against COVID-related Menstrual Changes.

New study on COVID-19, vaccination, and the menstrual cycle

There is a new study looking at the impact of both COVID-19 infection and vaccination on the menstrual cycle, so let’s review it!

There has been a fair bit written about the impact of COVID-19 vaccination on the length of the menstrual cycle. The consensus from several papers is there is a small lengthening of the cycle; specifically the period after vaccination is delayed by less than a day. 

But What About the Effect of COVID-19 Itself?

Before we go any further, changes in cycle length of up to seven days aren’t considered medically concerning. The menstrual cycle is not a metronome, so small variations are expected. We also know that about 5-6% of people will have a cycle that is eight days or more longer than expected, meaning even significant menstrual cycle irregularities are not uncommon. This is why it’s vital to always have menstrual cycle data from before an event, be it vaccination or an infection so that a person can be compared to their own baseline.

(As an aside, I read some very interesting studies about menstrual cycle recall for my upcoming book on the menstrual cycle, and I couldn’t discuss them all, but I am going to put up a post soon about them, so stay tuned!).

In a survey of women who had COVID-19, 47% reported a change in menstrual cycle regularity. It’s important to point out that this study has some serious limitations, specifically data on cycle length not collected prospectively and people with menstrual cycle changes may have been more likely to respond to the study. Unfortunately, because of these limitations, it’s not possible to say much more than, yes, there could be a link. Another study that was serendipitously already collecting data on menstrual cycle irregularities as well as collecting blood samples when the pandemic hit was able to test the blood for evidence of a previous infection with COVID-19 and compare menstrual cycle changes for those who had previously had an infection with those who had not. Having antibodies to COVID-19 meant there was a seven-fold greater chance of previously experiencing an irregular cycle, but this study was limited because the timing of the infection wasn’t known.   

The New Study

Published by Alvergne et al. in the journal Obstetrics & Gynecology looked at both the impact of COVID-19 infection and vaccination on the menstrual cycle. It’s a fantastic idea to look at both at the same time so researchers can see if one had a greater impact than the other. To accomplish this goal,  investigators turned to the period tracker app, Clue, looking at over 6,000 users from over 100 countries and evaluating just over 32,000 cycles. Data in Clue is recorded prospectively, which is important as previously mentioned.

A survey was sent to English-language users of the app about their history of COVID-19 infection as well as vaccination rates. Those using hormone contraception and those over age 45 were excluded. People with cycles longer than 38 days were excluded as were those who received two doses of the vaccine in 38 days or less–this excluded people who might have received two doses of the vaccine in the same menstrual cycle. The participants had to have five consecutive cycles of data and participants were divided into three groups: 

• No history of COVID-19 infection or vaccination 

• Vaccinated against COVID-19, but no history of having a COVID-19 infection. 

• People who had a previous COVID-19 infection, including both those who had been vaccinated at least 76 days (minimum of two cycles) before they developed COVID-19 and those who had not previously been vaccinated.

The investigators looked at three consecutive cycles before the “event” (either infection or vaccine) and two after, and for those who had neither had COVID-19 nor been vaccinated they chose the last three cycles of 2020 as the “before” and the first two cycles of 2021 as after. Once all these criteria were met, the investigators were left with 32,570 cycles from 421 people who served as controls, 1,450 with a history of COVID-19 infection, and 4,643 who were vaccinated. These kinds of numbers would be difficult to get from a prospective study, so this shows the power of mining app data.

It is important to note that COVID-19 status wasn’t verified with nasal swabs or blood work, although reporting a history of COVID-19 infection is apparently fairly accurate. This study also can’t count for asymptomatic infections. In addition, those who were very ill with COVID-19 would be less likely to have been included in this study, because if you are sick in the ICU or maybe just really sick at home, you may be less likely to collect menstrual cycle data, so this study can only give information on those people with COVID-19 who were well enough to record their menstrual cycle data in an app. 

What Were the Findings?

Among those who had COVID-19 but were not vaccinated there was a 1.45-day increase in menstrual cycle length in the cycle they had COVID-19 and cycles returned back to their baseline by the next cycle. 

Among those who were vaccinated, there was a 1.14-day increase in menstrual cycle length in the cycle they were vaccinated, which also returned to baseline by the following cycle. 

Interestingly, the impact on cycle length was statistically the same whether the person was in the infection group or the vaccine group. Meaning vaccination and infection resulted in a similar temporary small change in cycle length. 

The researchers also looked at the subgroup of people who had a lengthening in their cycle length of eight days or more, which is considered clinically significant. The breakdown is as follows:

• 6.9% for the control group

• 9.7% for the COVID-19 group

• 6.3% for the vaccinated group

Meaning a small percentage of people who develop COVID-19 may also develop a menstrual cycle irregularity of 8 days or more, that will resolve by the following cycle. For the vaccinated, this effect seems unlikely to occur. Meaning, vaccination against COVID-19 was protective against significant changes in the menstrual cycle for those who later go on to develop COVID-19. 

How Does This Stack Up With What We Know About COVID-19 Vaccination and the Menstrual Cycle?

Let’s compare this data with that collected from the Natural Cycles app and from the Apple Watch. The Natural Cycles app study looked at over 14,000 vaccinated individuals and more than 4,000 controls and the Apple Watch study had over 8,000 participants who had been vaccinated and more than 1,000 unvaccinated controls. Overall, the changes were a lengthening of the menstrual cycle post-vaccination by less than one day that reverted back to baseline by the next cycle. In the Natural Cycles study, the menstrual cycle was 0.55 days longer after the first dose of the mRNA vaccines and 0.29 days longer after the second dose. With the Apple Watch study, it was 0.50 days and 0.39 days longer for the first and second doses respectively. These changes are a little shorter than the 1.14 days in the Clue study just described but in the same ballpark. But we now have a pretty large body of evidence that tells us while there is an impact on the regularity of the menstrual cycle from vaccination, it is small and reverts back to the pre-vaccination baseline by the next cycle. 

In the Natural Cycles study, of those who received two doses in the same cycle, 13.5% had a temporary lengthening of their cycle of eight or more days. In this new study using the Clue data, the impact of COVID-19 vaccination prolonging the cycle by eight days or more wasn’t seen, meaning this effect is likely due to two doses per cycle (remember, there were no two doses per cycle in the new study). 

What Does This Add to What We Know about the Impact of COVID-19 Infection and Vaccination on the Menstrual Cycle?

Looking at these three large studies (Natural Cycles, Apple Watch, and Clue) we now have data from over 26,000 individuals who were vaccinated against COVID-19. When it comes to the impact of the vaccine on cycle length, it is reassuring three large studies have almost identical results. A small, temporary change. 

The findings from the new study showing a protective effect of vaccination on COVID-19-related menstrual cycle changes need to be verified with another study, and of course, we need more data for those who became very sick with COVID-19. 

All in all, the following seem fair conclusions:

• There is a small (meaning about a day or slightly less), but measurable effect of COVID-19 vaccination on lengthening the menstrual cycle that reverts to baseline the following cycle. 

• Significant changes in menstrual cycle length, meaning eight days or more, seem driven by those who receive two doses of the vaccine in the same cycle. This is something to look at in future studies so we can better advise people, and two it may teach us something new about the menstrual cycle.  

• Infection with COVID-19 that leaves one well enough to record menstrual data in an app seems to increase the risk of a significant change in the length of the menstrual cycle (meaning eight days or more) that reverts back to baseline. These changes happened to just under 10% of people who reported infection with COVID-19, compared with a baseline rate for these changes of just under 7%. More studies are needed. 

• COVID-19 vaccination may be protective against subsequent significant changes in menstrual cycle length, which I think is the most important and interesting takeaway from the study and a finding that deserve further evaluation.

If you like this kind of information on the menstrual cycle, I think you will like my new book Blood: The Science, Medicine, and Mythology of Menstruation, which is available for pre-order now in the US, Canada, UK, Australia, and New Zealand! Click here for a link. Look out for more menstrual cycle content in upcoming posts. 

References

1. Munro MG, Critchley HOD, Fraser IS. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynecol Obstet 2018;143:393–408. doi: 10.1002/ijgo.12666

2. Alison Edelman, MD, MPH, Emily R. Boniface, MPH, Eleonora Benhar, PhD, Leo Han, MD, MPH, Kristen A. Matteson, MD, MPH, Carlotta Favaro, PhD, Jack T. Pearson, PhD, and Blair G. Darney, PhD, MPHAssociation Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination. A U.S. Cohort. Obstet Gynecol 2022 https://journals.lww.com/greenjournal/Fulltext/9900/Association_Between_Menstrual_Cycle_Length_and.357.aspx

3. Edelman A et al. Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data, BMJMED 2022:1:e000297

4. Alvergne, Alexandra PhD; Boniface, Emily MPH; Darney, Blair PhD, MPH; Shea, Amanda PhD; Weber, Kirsten PhD; Ventola, Cécile PhD; Vitzthum, Virginia J. PhD; Edelman, Alison MD, MPH. Associations Among Menstrual Cycle Length, Coronavirus Disease 2019 (COVID-19), and Vaccination. Obstetrics & Gynecology ():10.1097/AOG.0000000000005343, August 10, 2023. | DOI: 10.1097/AOG.0000000000005343

5. Al-Najjar MAA, Al-Alwany RR, Al-Rshoud FM, Abu-Farha RK, Zawiah M. Menstrual changes following COVID-19 infection: a cross-sectional study from Jordan and Iraq. PLoS One 2022;17:e0270537. doi: 10.1371/journal.pone.0270537

6. Cherenack EM, Salazar AS, Nogueira NF, Raccamarich P, Rodriguez VJ, Mantero AM, et al. Infection with SARS-CoV-2 is associated with menstrual irregularities among women of reproductive age. PLoS One 2022;17:e0276131. doi: 10.1371/journal.pone.0276131