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

• Type of Material: Article
• Authors: Siwen Wang, Harvard T.H. Chan School of Public Health; Jasmine Mortazavi, Michigan State University; Jaime E Hart, Brigham and Women's Hospital; Jennifer A Hankins, Brigham and Women's Hospital; Laura M Katuska, Harvard T.H. Chan School of Public Health; Leslie V Farland, The University of Arizona; Audrey Gaskins, Emory University; Yi-Xin Wang, Harvard T.H. Chan School of Public Health; Rulla M Tamimi, Weill Cornell Medicine; Kathryn L Terry, Brigham and Women's Hospital; Janet W Rich-Edwards, Harvard T.H. Chan School of Public Health; Stacey A Missmer, Michigan State University; Jorge E Chavarro, Harvard T.H. Chan School of Public Health
• Language: English
• Date: 2022-11-01
• Publisher: Elsevier Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ajog.2022.07.003
• Title of Journal or Parent Work: American Journal of Obstetrics and Gynecology
• Volume: 227
• Issue: 5
• Start Page: 739.e1
• End Page: 739.e11
• Grant/Funding Information: This study was supported by research grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant numbers HD96033 and HD96033-03S1), contract from the National Institute for Occupational Safety and Health (contract number 75D30120P08255), and infrastructure grants from the National Heart, Lung, and Blood Institute (grant number U01HL145386) and from the National Institute of Environmental Health Sciences (NIEHS; grant number R24ES028521). S.W. was supported, in part, by the Zhejiang University Education Foundation Global Partnership Fund. J.E.H. was supported by a grant (grant number P30 ES000002) from the NIEHS.
• Keywords: SARS-CoV-2 infection; menstrual cycle length; COVID-19 vaccine; menstrual cycle change; menstrual health
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Epidemiology; Health Sciences, Nutrition

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: This study aimed to examine the associations of SARS-CoV-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 (0–6 months: odds ratio, 1.67 [95% confidence interval, 1.05–2.64]; 7–9 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 short-term 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.