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. 2022;1(1):e000297.
doi: 10.1136/bmjmed-2022-000297. Epub 2022 Sep 27.

Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data

Alison Edelman  1 , Emily R Boniface  1 , Victoria Male  2 , Sharon T Cameron  3 , Eleonora Benhar  4 , Leo Han  1 , Kristen A Matteson  5 , Agathe Van Lamsweerde  4 , Jack T Pearson  4 , Blair G Darney  1
Affiliations

Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data

Alison Edelman et al. BMJ Med. 2022.

Abstract

Objectives: To identify whether covid-19 vaccines are associated with menstrual changes in order to address concerns about menstrual cycle disruptions after covid-19 vaccination.

Design: Global, retrospective cohort study of prospectively collected data.

Setting: International users of the menstrual cycle tracking application, Natural Cycles.

Participants: 19 622 individuals aged 18-45 years with cycle lengths of 24-38 days and consecutive data for at least three cycles before and one cycle after covid (vaccinated group; n=14 936), and those with at least four consecutive cycles over a similar time period (unvaccinated group; n=4686).

Main outcome measures: The mean change within individuals was assessed by vaccination group for cycle and menses length (mean of three cycles before vaccination to the cycles after first and second dose of vaccine and the subsequent cycle). Mixed effects models were used to estimate the adjusted difference in change in cycle and menses length between the vaccinated and unvaccinated.

Results: Most people (n=15 713; 80.08%) were younger than 35 years, from the UK (n=6222; 31.71%), US and Canada (28.59%), or Europe (33.55%). Two thirds (9929 (66.48%) of 14 936) of the vaccinated cohort received the Pfizer-BioNTech (BNT162b2) covid-19 vaccine, 17.46% (n=2608) received Moderna (mRNA-1273), 9.06% (n=1353) received Oxford-AstraZeneca (ChAdOx1 nCoV-19), and 1.89% (n=283) received Johnson & Johnson (Ad26.COV2.S). Individuals who were vaccinated had a less than one day adjusted increase in the length of their first and second vaccine cycles, compared with individuals who were not vaccinated (0.71 day increase (99.3% confidence interval 0.47 to 0.96) for first dose; 0.56 day increase (0.28 to 0.84) for second dose). The adjusted difference was larger in people who received two doses in a cycle (3.70 days increase (2.98 to 4.42)). One cycle after vaccination, cycle length was similar to before the vaccine in individuals who received one dose per cycle (0.02 day change (99.3% confidence interval -0.10 to 0.14), but not yet for individuals who received two doses per cycle (0.85 day change (99.3% confidence interval 0.24 to 1.46)) compared with unvaccinated individuals. Changes in cycle length did not differ by the vaccine's mechanism of action (mRNA, adenovirus vector, or inactivated virus). Menses length was unaffected by vaccination.

Conclusions: Covid-19 vaccination is associated with a small and likely to be temporary change in menstrual cycle length but no change in menses length.

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Conflict of interest statement

Competing interests AE reports honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, World Health Organization, and Gynuity for committee activities and honorariums for peer review from the Karolinska Institute. AE receives royalties from UptoDate. Oregon Health and Science University (OHSU) receives research funding from OHSU Foundation, Merck, HRA Pharma, and the National Institutes of Health for which Alison Edelman is the principal investigator. BGD reports honorariums and travel reimbursement from the American College of Obstetricians and Society of Family Planning for board, committee, and mentorship activities. OHSU receives research funding from Merck/Organon and Office of Population Affairs/Department of Health and Human Services for which BGD is the principal investigator. OHSU receives research funding from OHSU foundation, the Bill & Melinda Gates Foundation, American Board of Obstetrics and Gynecology, American Society for Reproductive Medicine, and the National Institutes of Health for which Leo Han is the principal investigator. EB, AVL, and JTP are employees of Natural Cycles. Natural Cycles received cost reimbursement from grant funds for data processing and secure transfer. KAM reports honorariums and travel reimbursement from the American Board of Obstetrics and Gynecology and travel reimbursement from American College of Obstetricians and Gynecologists. Women and Infants Hospital received funding from Myovant for consulting work done by KAM on outcomes measures for heavy menstrual bleeding. VM reports research funding from Borne, payment for acting as an external examiner for the Universities of Cambridge, Leeds and Swansea, and royalties received for contribution to Immunology 9th edition (Elsevier). STC is the editor-in-chief of BMJ Sexual and Reproductive Health and reports an honorarium from Gedeon Richter Nordics for a lecture on contraception. ERB declares no competing interests.

Figures

Figure 1
Figure 1
Visual abstract
Figure 2
Figure 2
STROBE flow diagram
Figure 3
Figure 3
(Top row) Overlayed histograms of the change in cycle length (days) between the three prevaccination cycle average and the vaccination cycle for first dose (left) or second dose (right). Histograms for unvaccinated individuals are shown in yellow, vaccinated individuals are shown in purple. (Bottom row) Adjusted marginal means for cycle length (days) for the mean of the three prevaccination cycles and the vaccination cycle for first dose (left) or second dose (right). Estimates are from mixed effects models with random intercepts and random slopes at the individual level, an interaction between vaccination status and timing before and after vaccination, and adjusted for age, body mass index, educational attainment, parity, relationship status, and global region. Error bars represent 99.3% confidence intervals
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References

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