COVID-19 vaccination and menstrual cycle changes: A United Kingdom (UK) retrospective case-control study

Structured abstractO_ST_ABSObjectivesC_ST_ABSOur objectives were (1) to evaluate the prevalence of menstrual changes following vaccination against COVID-19, (2) to test potential risk factors for any such changes, and (3) to identify patterns of symptoms in participants written accounts. DesignA secondary analysis of a retrospective online survey titled "The Covid-19 Pandemic and Womens Reproductive Health", conducted in March 2021 in the UK before widespread media attention regarding potential impacts of SARS-CoV-2 vaccination on menstruation. SettingParticipants were recruited via a Facebook ad campaign in the UK. ParticipantsEligibility criteria for survey completion were age greater than 18 years, having ever menstruated and currently living in the UK. In total, 26,710 people gave consent and completed the survey. For this analysis we selected 4,989 participants who were pre-menopausal and vaccinated. These participants were aged 28 to 43, predominantly from England (81%), of white background (95%) and not using hormonal contraception (58%). Main outcome measureReports of any menstrual changes (yes/no) following COVID-19 vaccination and words used to describe menstrual changes. ResultsAmong pre-menopausal vaccinated individuals (n=4,989), 80% did not report any menstrual cycle changes up to 4 months after their first COVID-19 vaccine injection. Current use of combined oral contraceptives was associated with lower odds of reporting any changes by 48% (OR = 0.52, 95CI = [0.34 to 0.78], P<0.001). Odds of reporting any menstrual changes were increased by 44% for current smokers (OR = 1.16, 95CI = [1.06 to 1.26], P<0.01) and by more than 50% for individuals with a positive COVID status [Long Covid (OR = 1.61, 95CI = [1.28 to 2.02], P<0.001), acute COVID (OR = 1.54, 95CI = [1.27 to 1.86], P<0.001)]. The effects remain after adjusting for self-reported magnitude of menstrual cycle changes over the year preceding the survey. Written accounts report diverse symptoms; the most common words include "cramps", "late", "early", "spotting", "heavy" and "irregular", with a low level of clustering among them. ConclusionsFollowing vaccination for COVID-19, menstrual disturbance occurred in 20% of individuals in a UK sample. Out of 33 variables investigated, smoking and a previous history of SARS-CoV-2 infection are found to be risk factors while using oestradiol-containing contraceptives was found to be a protective factor. Diverse experiences were reported, from menstrual bleeding cessation to heavy menstrual bleeding. Summary boxO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LIMenstrual disturbances including changes in frequency and/or dysmenorrhoea following vaccination have been reported as early as 1913 for the typhoid vaccine (1). Since then there have only been a few studies investigating this topic, using small sample sizes (hepatitis vaccine (2)) or reporting mixed results (HPV vaccine (3,4)). C_LIO_LIThe UKs Medicine and Healthcare products Regulatory Agency (MHRA) is closely monitoring reports of menstrual disorders, with more than 30,000 reports made to its yellow card surveillance scheme by 2 September 2021 following vaccination with both mRNA and adenovirus-vectored COVID-19 vaccines (5). C_LIO_LIIn a recent preprint of a retrospective case-control study of 21,380 pre-menopausal participants living in the US, 45.8% of 9,579 people with regular menstrual cycles experienced heavier bleeding after COVID-19 vaccination. In addition, 70.5% of 1,545 non-menstruating people using long-acting reversible contraceptives (LARC) experienced breakthrough bleeding after COVID-19 vaccination (6). This informative study may be affected by selection bias and may not be generalisable. C_LI What this study addsO_LIIn a large sample of participants vaccinated against COVID-19 surveyed in the UK before widespread media attention to related menstrual changes, the prevalence of menstrual changes was 1 in 5. C_LIO_LIOut of 33 socio-demographic, health, vaccine, COVID- and pandemic-related and reproductive variables, the odds of reporting any menstrual changes following COVID-19 vaccination were associated with a history of SARS-CoV-2 infection, smoking behaviour and the type of contraceptives used. C_LIO_LIMenstrual changes that were reported were diverse, ranging from increased bleeding to the cessation of bleeding. C_LIO_LIThe study highlights the need for greater consideration of the menstrual cycle in health interventions. C_LI