A number of menstrual cycle changes have been reported following COVID-19 vaccination, including both longer, shorter, and absent cycles, heavier and lighter menstrual flow, and spotting. However, no results related to menstrual cycles have been collected in clinical trials of COVID-19 vaccines. A group of US researchers has now investigated this.
Menstruation routinely accompanies women for about 40 years of their lives. Although small changes in menstrual characteristics may not matter to clinicians and researchers, they are noticed by those affected, may be alarming, and may contribute to vaccination hesitancy, write Dr. Alison Edelman, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, and colleagues [1]. According to them, the lack of evidence on vaccines and menstrual health, combined with long-standing gender-based research inequities, could also be interpreted by the public as rejection from the scientific and medical community.
A previous study by the research group was the first to show an association between COVID-19 vaccines and menstrual cycle changes [2]. However, only U.S. residents were included. Following the global introduction of the vaccine, a broader analysis has now been made. The global, retrospective cohort study included 19 622 participants aged 18-45 years with cycle lengths of 24-38 days and prospectively collected data for at least three cycles before and one cycle after COVID (vaccinated group; n=14 936) or those with at least four consecutive cycles over a similar period (unvaccinated group; n=4686).
The objective of the study was to determine whether COVID-19 vaccines are associated with menstrual changes to address concerns about menstrual cycle disturbances following vaccination. Mean change within participating women was assessed by vaccination group for cycle and menstrual duration (mean of three cycles before vaccination to cycles after the first and second doses of vaccine and the subsequent cycle). Mixed-effects models were used to estimate the adjusted difference in change in menstrual cycle and length of menstruation between the vaccinated and unvaccinated.
Minor changes in cycle length
80.08% of women were younger than 35 years and were from the United Kingdom (31.71%), the United States and Canada (28.59%), or Europe (33.55%). Two-thirds (66.48%) of the vaccinated cohort received the Pfizer-BioNTech vaccine (BNT162b2), 17.46% received Moderna (mRNA-1273), 9.06% received AstraZeneca (ChAdOx1 nCoV-19), and 1.89% (n=283) received Johnson & Johnson (Ad26.COV2.S).
In vaccinated subjects, compared with nonvaccinated subjects, there was an adjusted increase of less than one day in the length of the first and second vaccination cycles (increase of 0.71 days, 99.3% CI 0.47-0.96, for the first dose; increase of 0.56 days, 99.3% CI 0.28-0.84, for the second dose) (Fig. 1). The adjusted difference was greater in subjects who received two doses in one cycle (increase of 3.70 days, 2.98 to 4.42). One cycle after vaccination, cycle length was similar to prevaccination in women who received one dose per cycle (0.02-day change; 99.3% CI -0.10-0.14) but not yet in those who received two doses per cycle (0.85-day change; 99.3% CI 0.24-1.46) compared with unvaccinated individuals. Changes in cycle length did not differ by vaccine mechanism of action (mRNA, adenovirus vector, or inactivated virus). Menstrual length was not affected by vaccination.
The proportion of individuals with a clinically significant change in cycle length of eight days or more was significantly higher in the vaccinated group during both the first and second vaccination cycles (6.2% (929 of 14 936 for the first dose and 597 of 9600 for the second dose) compared to 5.0% (236 of 4686 for the first dose and 222 of 4423 for the second dose) in the unvaccinated for both cycles; adjusted p-value=0.019 for the first dose and 0.034 for the second dose). In vaccinated subjects, unadjusted cycle length returned to its prevaccination average in the cycle after the second dose, referred to as the postvaccination cycle (0.09; 99.3% CI -0.03-0.20). The unvaccinated cohort had a small but significant increase similar to the vaccination cycle with the second dose (0.20; 99.3% CI 0.01-0.39). After adjustment for confounders, no significant difference in cycle length change was reported between vaccination groups (-0.11; 99.3% CI -0.33-0.10), indicating resolution of cycle changes associated with vaccination.
“Reassuring results”
Compared with the unvaccinated group, vaccinated subjects had an adjusted increase in menstrual cycle length of less than one day at both the first and second vaccine doses. Women who received two doses of COVID-19 vaccine in a single cycle had an adjusted increase in cycle length of 3.70 days compared with the unvaccinated.
In addition, a significant increase was noted in individuals in whom cycle length was extended by more than eight days (13.5% compared with 5.0% in the unvaccinated cohort). Changes in cycle length did not persist after vaccination, except in the group that received two doses of vaccine in one cycle, where changes in cycle length attenuated compared with the nonvaccinated group but were still increased. Changes in cycle length due to COVID-19 vaccination appear to be similar across vaccine types. The results are thus consistent with those from their earlier study in a U.S.-only cohort and provide further evidence of minor changes in cycle length associated with COVID-19 vaccination, the authors explain.
He said the results remain reassuring and can be used to counsel women about what to expect with COVID-19 vaccination and how to make an informed decision about vaccination versus continued risk for COVID-19 disease and associated morbidity and mortality. Although menstrual changes are seen after COVID-19 vaccination, these changes are small compared to normal variations and resolve in the postvaccination cycle, he said, except for women who received both doses in one menstrual cycle. Future work should evaluate other aspects of menstrual cycle changes, such as unexpected vaginal bleeding, menstrual flow, and pain, and define the mechanism by which the changes occur after vaccination, the researchers conclude.
Literature:
- Edelman A, Boniface ER, Male V, et al: Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data. BMJ Medicine 2022; 1: e000297; doi: 10.1136/bmjmed-2022-000297.
- Edelman A, Boniface ER, Benhar E, et al: Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination: A U.S. Cohort. Obstetrics & Gynecology 2022; 139(4): 481-489; doi: 10.1097/AOG.0000000000004695.
InFo PNEUMOLOGY & ALLERGOLOGY 2022; 4(4): 28-29.
