A prospective study of the association between SARS-CoV-2 infection and COVID-19 vaccination with changes in usual menstrual cycle characteristics.
Academic Article
Overview
abstract
BACKGROUND: Despite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated. OBJECTIVE: To examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics. STUDY DESIGN: We prospectively followed 3,858 pre-menopausal women in the Nurses' Health Study 3 (NHS3) 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 "pre-COVID" (reported at baseline between 2011-2016) and "post-COVID" (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 (1) SARS-CoV-2 infection and (2) COVID-19 vaccination and change in menstrual cycle characteristics. RESULTS: The median age at baseline and 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. We documented 421 (10.9%) SARS-CoV-2 infections and 3,527 (91.4%) vaccinations during follow-up. Vaccinated women had a higher risk of increased cycle length compared to those unvaccinated (OR=1.54, 95% CI=1.04-2.27), after adjusting for sociodemographic and behavioral factors. These associations were similar after additionally accounting for pandemic-related stress. COVID-19 vaccination was only associated with change to longer cycles in the first 6 months after vaccination (0-6 months: OR=1.72, 95% CI=1.08-2.73; 7-9 months: OR=1.49, 95% CI=1.00-2.23; >9 months: OR=1.44, 95% CI=0.93-2.22) and among women whose cycles were short, long or irregular before vaccination (OR=2.87, 95% CI=1.54-5.35; OR=1.03, 95% CI=0.60-1.75 for women with normal length, regular cycles before vaccination). mRNA and adenovirus-vectored vaccines were both associated with this change. SARS-CoV-2 infection was not associated with changes in usual menstrual cycle characteristics. CONCLUSIONS AND RELEVANCE: COVID-19 vaccination may be associated with short-term changes in usual menstrual cycle length, particularly among women whose cycles were short, long or irregular before vaccination. These results underscore the importance of monitoring menstrual health in vaccine clinical trials. Future work should examine the potential biological mechanisms.
