A prospective study of the association between SARS-CoV-2 infection and COVID-19 vaccination with changes in usual menstrual cycle characteristics

BACKGROUND: Despite anecdotal reports, the impacts of SARS-CoV2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated. OBJECTIVE: This study aimed to examine the associations of SARSCoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics. STUDY DESIGN: This study prospectively observed 3858 premenopausal women in the Nurses' Health Study 3 living in the United States or Canada who received biannual follow-up questionnaires between January 2011 and December 2021 and completed additional monthly and quarterly surveys related to the COVID-19 pandemic between April 2020 and November 2021. History of positive SARS-CoV-2 test, COVID-19 vaccination status, and vaccine type were self-reported in surveys conducted in 2020 and 2021. Current menstrual cycle length and regularity "before COVID-19" were reported at baseline between 2011 and 2016, and current menstrual cycle length and regularity "after COVID-19" were reported in late 2021. Pre- to post-COVID change in menstrual cycle length and regularity was calculated between reports. Logistic or multinomial logistic regression models were used to assess the associations between SARS-CoV-2 infection and COVID-19 vaccination and change in menstrual cycle characteristics. RESULTS: The median age at baseline and the median age at end of follow-up were 33 years (range, 21-51) and 42 years (range, 27-56), respectively, with a median follow-up time of 9.2 years. This study documented 421 SARS-CoV-2 infections (10.9%) and 3527 vaccinations (91.4%) during follow-up. Vaccinated women had a higher risk of increased cycle length than unvaccinated women (odds ratio, 1.48; 95% confidence interval, 1.00-2.19), after adjusting for sociodemographic and behavioral factors. These associations were similar after in addition accounting for pandemic-related stress. COVID-19 vaccination was only associated with change to longer cycles in the first 6 months after vaccination (0e6 months: odds ratio, 1.67 [95% confidence interval, 1.05e2.64]; 7e9 months: odds ratio, 1.43 [95% confidence interval, 0.96-2.14]; >9 months: odds ratio, 1.41 [95% confidence interval, 0.91-2.18]) and among women whose cycles were short, long, or irregular before vaccination (odds ratio, 2.82 [95% confidence interval, 1.51-5.27]; odds ratio, 1.10 [95% confidence interval, 0.68-1.77] for women with normal length, regular cycles before vaccination). Messenger RNA and adenovirus-vectored vaccines were both associated with this change. SARS-CoV-2 infection was not associated with changes in usual menstrual cycle characteristics. CONCLUSION: COVID-19 vaccination may be associated with shortterm changes in usual menstrual cycle length, particularly among women whose cycles were short, long, or irregular before vaccination. The results underscored the importance of monitoring menstrual health in vaccine clinical trials. Future work should examine the potential biological mechanisms.