A recent study published in the BMJ evaluated the risks of menstrual disturbance and bleeding after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in pre- or post-menopausal females.

Background

Menstrual disturbances have been reported to be associated with SARS-CoV-2 vaccines. Studies indicate menstrual cycle changes following vaccination. Nonetheless, menstrual cycles vary naturally; minor disturbances in menstruation are generally not clinically important. But these changes can be distressful for those affected, particularly during mass vaccination when concerns emerge about adverse reactions.

While pharmacovigilance systems that rely on self-reports can identify potential safety signals, they are unsuited for estimating the frequency of health events and the strength of a potential association. As such, individual-level data are required from extensive observational studies to characterize and quantify the adverse effects of SARS-CoV-2 vaccines.

About the study

In the present study, researchers assessed the risks of menstrual disturbance and bleeding following SARS-CoV-2 vaccination in pre- or post-menopausal females. They included females aged 12-74 living in Sweden on January 1, 2018, who were still Swedish residents when vaccination commenced on December 27, 2020. Subjects were excluded if they lived at special care facilities, were pregnant, had a history of breast cancer, menstruation disorders, or underwent a hysterectomy.

The team considered two risk windows – one to seven days and eight to 90 days post-vaccination and assessed the risk of menstrual disorders during these periods after each dose. Further, analyses were stratified by vaccine product (BNT162b2, mRNA-1273, and ChAdOx1). Additionally, they examined the menstrual disorder risks in non-vaccinated females following SARS-CoV-2 infection. The primary analyses were performed for the whole study population.

Additional analyses were performed for a subpopulation from Stockholm and Västra Götaland regions with primary healthcare data available. The researchers studied three menstrual disorders (outcomes) across restricted age groups based on healthcare contact, i.e., visit/admission to a hospital. They investigated post-menopausal bleeding in females aged 45-74 and pre-menopausal bleeding and menstrual disturbances in those aged 12-49.

Findings

Overall, more than 2.9 million females were included. Of these, 87.6% had been partially vaccinated by February 28, 2022. More than 1.6 million participants were triple vaccinated. Most diagnoses (99%) of bleeding disorders or menstrual disturbance in the overall cohort were from outpatient care. Around 11% and 19% of diagnoses of (pre- or post-menopausal) bleeding disorders and menstrual disturbance were documented in the subpopulation with primary healthcare data, respectively.

Nearly 26% of the study cohort tested SARS-CoV-2-positive between August 1, 2020, and December 25, 2020. The adjusted hazard ratio for the risk of post-menopausal bleeding after any vaccine dose was 1.12 during the first risk window and 1.14 in the second risk window relative to the non-vaccinated period. The highest risk was after receiving the third dose in both risk windows. There was a similar trend for the subpopulation, albeit the risk estimates were generally lower.  

When analyses were restricted to females without previous hormone treatment, the risk estimates were slightly higher than in the primary analysis, with the highest risk observed after the third vaccination. The risk of post-menopausal bleeding was 41% and 23% higher after the third BNT162b2 dose in the first and second risk windows, respectively. The risk was 33% higher after the third mRNA-1273 dose in the second risk window.

The adjusted hazard ratios after any vaccine dose for menstrual disturbance were 1.13 and 1.06 in the first and second risk windows, respectively, relative to the non-vaccinated period. Estimates were similar for the subpopulation. Vaccine product-specific estimates for menstrual disturbance were consistent with overall risk estimates.

The adjusted hazard ratios following any vaccine dose for pre-menopausal bleeding were 1.08 and 1.01 in the 1-7 and 8-90 risk windows, respectively, with similar estimates for the subpopulation. Vaccine product-specific estimates for pre-menopausal bleeding were imprecise. The risk for three outcomes was lower within one week after a positive SARS-CoV-2 test but increased modestly within 90 days, notably for bleeding disorders.

Conclusions

In summary, the researchers observed a weak/inconsistent association of SARS-CoV-2 vaccination with healthcare contact for post-menopausal bleeding, with even less evidence (of association) with menstrual disturbance or pre-menopausal bleeding.

Overall, the results do not substantially support causal associations between vaccination and healthcare contact for bleeding/menstrual disorders.