COVID-19 shots temporarily mess up menstrual cycle length

Women who receive COVID-19 jabs may experience short-term changes in their menstrual cycle length, particularly those who have short, long, or irregular cycles prior to vaccination, a study has found.

“In this prospective study … COVID-19 vaccination was associated with an increase in usual menstrual cycle length, after adjusting for potential confounders including local COVID-19 burden and pandemic-related stressors,” according to the investigators.

Vaccinated women were 1.5 times as likely as their unvaccinated counterparts to experience a longer menstrual cycle (odds ratio [OR], 1.54, 95 percent confidence interval [CI], 1.04–2.27). This change in cycle length appeared to be limited to the 6-month period following vaccination (0–6 months: OR, 1.72, 95 percent CI, 1.08–2.73; 7–9 months: OR, 1.49, 95 percent CI, 1.00–2.23; >9 months: OR, 1.44, 95 percent CI, 0.93–2.22). [Am J Obstet Gynecol 2022;doi:10.1016/j.ajog.2022.07.003]

Of note, the association was more pronounced among women whose cycles were short, long, or irregular before vaccination (OR, 2.87, 95 percent CI, 1.54–5.35) than among those with normal length and regular cycles (OR, 1.03, 95 percent CI, 0.60–1.75). Furthermore, the increases in usual cycle length after vaccination were seen with both mRNA and adenovirus-vectored COVID-19 vaccines.

“Our findings suggest the need to monitor menstrual cycle health in vaccine clinical trials and increased attention to sex-based differences in vaccine response, especially in the setting of the rollout of COVID-19 boosters, which provides another opportunity to study this important issue,” the investigators said.

A consequence of immune response

These data are in line with the United Kingdom Medicine and Healthcare products Regulatory Agency (MHRA) documentation and three retrospective studies reporting short-lived changes in cycle length or flow, with longer cycles and heavier flows, following COVID-19 vaccination. [tinyurl.com/yd4429xk; Sci Adv 2022;doi:10.1126/sciadv.abm7201; tinyurl.com/23wqwkuf; medRxiv 2021;doi:10.1101/2021.11.23.21266709v1]

“There are multiple plausible mechanisms to explain the observed association, including immunological influences on sex hormones and systemic inflammatory responses that may invoke downstream responses in target organs,” according to the investigators. [Aging Cell 2015;14:309-321; Mayo Clinic Proceedings 2020;95:1710-1714]

“A normal menstrual cycle is characterized by tightly regulated inflammatory and immune mediators that facilitate the endometrial tissue breakdown and degradation needed for menstruation… [So], the immune response induced by both mRNA and adenovirus-vectored vaccines may temporarily affect the hypothalamic-pituitary-ovarian axis, which could lead to menstrual disturbances,” they explained. [New Engl J Med 2020;doi:10.1056/nejmoa2034577; Immunology 2020;doi:10.1111/imm.13136; Womens Health 2013;9:387-395]

The present study included 3,858 premenopausal women (median age at baseline 33 years) in the Nurses’ Health Study 3 living in the United States or Canada, with a median follow-up time of 9.2 years. A total of 421 (10.9 percent) participants contracted SARS-CoV-2 infections, and 3,527 (91.4 percent) received vaccinations during follow-up.

The median time from vaccination to end of follow-up was 8.7 months among women infected with SARS-CoV-2 and 8.5 months among vaccinated women. Overall, 2,227 women reported a change in either cycle length (n=1,408) or regularity (n=1,735) during follow-up.

A strength of the study, according to the investigators, was the collection of sufficient information, which allowed comparison between those uninfected and unvaccinated, as well as examination of changes in menstrual cycle characteristics prior to the pandemic. However, they also acknowledged that the findings might be limited by self-reported menstrual cycle characteristics and SARS-CoV-2 infection and the inclusion of mainly healthcare workers with a high vaccination rate, among others.