Menstrual abnormalities after COVID‐19 vaccination in the Netherlands: A description of spontaneous and longitudinal patient‐reported data

Abstract

AimsDuring the COVID‐19 vaccination campaigns, the number of reports of menstrual abnormalities increased rapidly. Here, we describe the nature and potential risk factors associated with menstrual abnormalities based on spontaneously reporting data as well as data from a prospective cohort event monitoring (CEM) study as these are poorly studied.MethodsReports of menstrual abnormalities received by the Netherlands Pharmacovigilance Centre Lareb in the spontaneous reporting system between February 2021 and April 2022 were summarized. In addition, logistic regression analysis was performed on the reported menstrual abnormalities in the CEM study to assess the association between person characteristics, prior SARS‐CoV‐2 infection and use of hormonal contraceptives and the occurrence of menstrual abnormalities after vaccination.ResultsWe analysed over 24 000 spontaneous reports of menstrual abnormalities and over 500 episodes (among 16 929 included women) of menstrual abnormalities in the CEM study. The CEM study showed an incidence of 41.4 per 1000 women aged ≤54 years. Amenorrhoea/oligomenorrhoea and heavy menstrual bleeding collectively accounted for about half of all abnormalities reported. Significant associations were observed for the age group 25–34 years (odds ratio 2.18; 95% confidence interval 1.45–3.41) and the Pfizer vaccine (odds ratio 3.04; 95% confidence interval 2.36–3.93). No association was observed for body mass index and presence of most comorbidities assessed.ConclusionThe cohort study showed a high incidence of menstrual disorders among women aged ≤54 years, and this observation was supported by the analysis of spontaneous reports. This suggests that a relation between COVID‐19 vaccination and menstrual abnormalities is plausible and should be further investigated.

Menstrual disorders following COVID-19 vaccination: a review using a systematic search

“…Bisgaard Jensen et al mentioned that change in menstrual cycle length was the most frequently reported change (9% longer menstrual cycles and 7% shorter menstrual cycles (Bisgaard Jensen et al, 2023). In the study by Duijster et al, amenorrhoea/ oligomenorrhoea was also the most reported menstrual outcome (33% of 24,090 spontaneous reports) (Duijster et al, 2023). Caspersen et al found a longer interval in girls aged 12-15 years (RR = 1.15, 95%CI 1.05-1.27), and in girls aged 14-15 years (RR = 1.17, 95%CI 1.05-1.31).…”

“…Different results were found regarding menstrual disorders after specific COVID-19 vaccine brands. Some studies did not find differences between the vaccine brands AstraZeneca, Johnson & Johnson, Moderna, and Pfizer (Alvergne et al, 2022;Muhaidat et al, 2022;Qashqari et al, 2022;Rogers et al, 2022;Alvergne et al, 2023b;Darney et al, 2023;Saleh Alzahrani et al, 2023;Wali et al, 2023), whereas others found that Pfizer (Wong et al, 2022;Al-Furaydi et al, 2023;Duijster et al, 2023;Filfilan et al, 2023), Moderna (Alahmadi et al, 2022;Trogstad et al, 2023), or AstraZeneca (Filfilan et al, 2023) resulted in a higher rate of menstrual changes compared to other COVID-19 vaccines.…”

“…Although the use of non-hormonal intrauterine devices was positively correlated with excessive bleeding in one study (Issakov et al, 2022;Alvergne et al, 2023b) found that hormonal contraception decreased the risk of reporting menstrual changes by 50%, Farland et al (Farland et al, 2022) found that using any hormonal medication decreased the risk of menstrual cycle changes by 27% (OR = 0.73; 95%CI 0.49-1.08), and (Bisgaard Jensen et al, 2023) found lower odds of reporting any menstrual change (OR = 1.71; 95%CI 0.65-0.78). Two studies did not find an association between hormonal contraceptives and menstrual abnormalities (Muhaidat et al, 2022;Duijster et al, 2023). Other significant associated factors that increased the risk were age (Lee et al, 2022;Morsi et al, 2022;Farah et al, 2023), greater body mass index (Farland et al, 2022), number of children (Muhaidat et al, 2022), marital status (Morsi et al, 2022;Muhaidat et al, 2022), smoking (Alvergne et al, 2023b), education level (Farah et al, 2023), being Hispanic of Latinx (Lee et al, 2022), and high selfreported perceived stress levels (Farland et al, 2022;Bisgaard Jensen et al, 2023).…”

“…Menstrual disorders are abnormalities in the menstrual cycle and include changes in the menstrual cycle length, changes in menses length, changes in the amount of bleeding, changes in the experience of (pre)menstrual pain, intermenstrual bleeding, and post-menopausal bleeding (Shapley et al, 2004). Although menstrual disorders are common in women, frequencies of these self-reported outcomes are difficult to estimate (Duijster et al, 2023;Trogstad et al, 2023). Several factors may influence the menstrual cycle, such as lifestyle factors, biological factors, and environmental factors (Campbell et al, 2021).…”

“…The PRAC is the committee of the EMA and is responsible for assessing and monitoring the safety of human medicines (European Medicines Agency, 2023). Continuous monitoring, early detection, and providing information on possible adverse events is of critical importance to objectively advise the society on the use of drugs and vaccines (Duijster et al, 2023). In other countries, similar systems and organizations for vaccine safety monitoring exist; For instance, the Vaccine Adverse Event Reporting System (VAERS) is the early warning system that monitors the safety of vaccines after they are authorized or licensed for use by the U.S. Food and Drug Administration (FDA).…”