COVID-19 Vaccination and the Menstrual Cycle: Impact of Timing

Looking at the latest study

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Researchers are continuing to look at the impact of COVID-19 vaccination on the menstrual cycle, and a new study published in the journal Obstetrics and Gynecology provides us with more insight into the timing of vaccination in the cycle and any subsequent impact. As with previous studies examining a potential connection between the COVID-19 vaccine and the menstrual cycle, it’s reassuring. 

The study evaluates data collected by the menstrual tracking app Natural Cycles (as have several previous studies). Menstrual tracking apps are an ideal way to record a large amount of data in real time, allowing researchers to go back and mine historical menstrual records. This prospectively collected data is essential as there are typically many inaccuracies in mentally recalling menstrual cycle dates. 

What We Previously Learned from the Natural Cycles Data 

Researchers previously looked at data from over 19,000 people (more than 14,000 who were vaccinated and more than 4,0000 who were unvaccinated and who served as controls), totaling more than 250,000 menstrual cycles. So, there was a lot of data! Vaccination against COVID-19 was associated with a statistically significant increase in the menstrual cycle length of 0.71 days. Interestingly, this small change was primarily the result of people who received two doses in one cycle, and for them, their vaccine cycle was an average of 3.7 days longer. It’s important to note that the length of the menstrual cycle can normally vary by seven days from cycle to cycle, so while some people may notice this change, it isn’t medically concerning, especially as the menstrual cycle returned to its pre-vaccination baseline by the next cycle. Looking at a change of eight days or more, something that is considered medically notable, there was no difference between those who received one dose of the vaccine compared with those who were unvaccinated. However, among those who received two doses within one cycle, 13.5% had an increase in cycle length of eight days or more. 

This led to the hypothesis that it isn’t the two doses that matter, but rather, when two doses are administered, the first one is given early in the cycle, and this is the window of time to potentially effect a change. This hypothesis is based on the idea that immune stimulation from the vaccine could affect the early signaling from the brain to the ovary (also known as the hypothalamic-pituitary axis or what I like to call the brain-brain-ovary connection) that rouses the follicles (eggs), eventually leading to a dominant follicle that ovulates. There is more flexibility in this first part of the cycle (known as the follicular phase), and when people have a variation in their cycle length that is unrelated to vaccination, it is almost always due to changes in the length of the follicular phase. Once ovulation has occurred (the luteal phase), the brain is no longer involved, so to speak, and it’s up to the progesterone produced by the corpus luteum (the tissue left over after an egg ovulates). It is highly unlikely the lifespan of the corpus luteum could be extended by a vaccine (or by any mechanism), thereby prolonging the cycle, which means, based on what we know, an effect on the corpus luteum seems unlikely.  

If you want to read more about the brain-brain-ovary axis, there is an entire chapter in my new book Blood. 

Enter the Latest Study

To test the hypothesis that the impact of the COVID-19 vaccine on the menstrual cycle is related to administration in the follicular phase, researchers identified 19,497 individuals in the Natural Cycles database who had at least four consecutive cycles of data: 9,279 who were vaccinated in their follicular phase, 5,532 who were vaccinated in their luteal phase, and 4,686 unvaccinated people as controls. As with previous studies looking at this data set, each patient served as their control, comparing their post-vaccination and pre-vaccination cycles. 

The results?

There was no change in cycle length when the vaccine was given in the luteal phase versus controls, but when the vaccine was given in the follicular phase, the average cycle lengthened by one day. This was the same whether it was the first dose of the vaccine or a second dose. There was a trend for the change in cycle length being slightly greater when the vaccine was given in the first half of the follicular phase versus the second half. 

The researchers also looked to see who experienced a medically notable change in their cycle length, meaning a lengthening of 8 or more days. Here is how the results broke down:

A change in menstrual cycle length of eight days or more occurred in any given cycle for 5 % of people. This means some people will have a change in their cycle unrelated to the vaccine.

When the vaccine was given in the follicular phase, there was a greater chance of a significantly prolonged cycle. Although overall, the percentage of people affected was low. 

What Does This Mean? 

This study supports the hypothesis that inflammatory mediators normally released in response to vaccination impact signaling from the brain to the ovaries during the follicular phase. The net result is a small delay in follicle (egg) development in the ovaries. While this change is statistically significant, a delay of one day is not medically notable. However, a small percentage of people will have a delay in their next cycle of eight or more days. Previous research tells us this reverts back to baseline by the next cycle, akin to what happens when people get swollen lymph nodes after a vaccine. It’s a temporary and reversible but not medically concerning response to the immune system activation. 

What We Don’t Know

This study excluded people who likely had polycystic ovarian syndrome (cycles needed to be every 24-38 days, which is the typical range) and those in the menopause transition, so we don’t know what these populations can expect. When menstrual cycles are irregular and unpredictable, trying to determine any potential impact of the vaccine is likely to be challenging. 

This study didn’t tell us about the heaviness of flow post-vaccination, so we don’t know if that is also linked with vaccination earlier in the cycle. Researchers have previously looked at the impact of vaccination against COVID-19 on the heaviness of flow, and it affects about 4% of people in their first post-vaccination menstruation. 

We also don’t know if the vaccine can trigger bleeding between periods, but this seems to be unlikely based on what we have learned so far. Finally, we don’t know much about the impact of COVID-19 vaccination on menstrual pain and if that would be different for those with baseline painful periods (primary dysmenorrhea) or endometriosis. 

Ideally, this finding should be replicated by another group using a different database before it is accepted, and studies to help us understand how the immune system drives this effect and why it only happens to some people are needed. 

Does this Affect When People Should be Vaccinated?

If someone had an early follicular phase COVID-19 vaccination and told me they had more than a seven-day delay in their next cycle and wanted to avoid that change if possible with their booster, I’d suggest they get any subsequent COVID-19 vaccinations in their luteal phase as long as that didn’t present an obstacle to getting vaccinated. It’s always better to get boosted; vaccine delays can become vaccine misses.

We can’t translate this data to other vaccines, as different vaccines elicit different responses from the immune system. For example, we don’t have any data to tell us if the influenza vaccine has the same potential to impact the menstrual cycle for a small percentage of people as the COVID-19 vaccine. However, if someone told me they had a very heavy period post-COVID-19 vaccination or were bothered by a delay in their cycle of eight or more days, I’d offer other vaccines (e.g., HPV, influenza, etc.) in the luteal phase, understanding this is based on no real evidence, just making the best guess while explaining this could always be a wrong guess.

Bottom Line:

Hopefully, people will find this information reassuring, and going forward, more studies will look at the impact of vaccines on the menstrual cycle. I am confident that, with time and appropriate funding, we will understand what parts of the immune response are responsible for the impact of the COVID-19 vaccine on the brain-brain-ovary connection because this may allow us to come up with strategies to prevent any changes and may teach us more about the intricate hormone signaling required for the menstrual cycle. 

References

1. Edelman A et al. Timing of Coronavirus Disease 2019 (COVID-19) Vaccination and Effects on Menstrual Cycle Changes. Obstet Gynecol ():10.1097/AOG.0000000000005550, February 27, 2024. | DOI: 10.1097/AOG.0000000000005550

2. Darney BG, et al. Impact of coronavirus disease 2019 (COVID-19) vaccination on menstrual bleeding quantity: An observational cohort study. BJOG 10 April 2023 https://doi.org/10.1111/1471-0528.17471.

3. Trogstad, Lill, Increased Occurrence of Menstrual Disturbances in 18- to 30-Year-Old Women after COVID-19 Vaccination (January 1, 2022). Available at SSRN: https://ssrn.com/abstract=3998180 or http://dx.doi.org/10.2139/ssrn.3998180.

4. Edelman A, et al. Association 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.

5. 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.

6. Alvergne A, et al. Effect of COVID-19 vaccination on the timing and flow of menstrual periods in two cohorts. Front. Reprod. Health, 25 July 2022 Sec. Gynecology. Volume 4 - 2022 | https://doi.org/10.3389/frph.2022.952976.

7. 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

8. Hall OJ et. al. Progesterone-Based Contraceptives Reduce Adaptive Immune Responses and Protection against Sequential Influenza A Virus Infections. J Virol. 2017 Mar 29;91(8):e02160-16. doi: 10.1128/JVI.02160-16. PMID: 28179523; PMCID: PMC5375688.