(102) Evaluation of postmenopausal hemorrhage following Moderna COVID-19 vaccines: results from surveillance data analysis and interim results from a US claims database cohort study

Background: Vaginal bleeding ≥12 months after the final menstrual period in the absence of hormone replacement therapy or pelvic surgery is known as postmenopausal hemorrhage (PMH). While cases have been reported following COVID-19 vaccines, an association has not been established.

Objectives: To assess risk of PMH following Moderna COVID-19 vaccines using both data from Moderna’s global safety database (GSD) and a US population-based cohort study.

Methods: As of 17OCT23, spontaneously reported PMH cases after a Moderna COVID-19 vaccine were identified from the Moderna’s GSD using the MedDRA preferred term “Postmenopausal hemorrhage”. Observed to expected (OE) analysis was performed for females ≥ 40 years of age. Reporting rates were estimated by dividing observed PMH cases by person-time risk (21-days after each dose of Moderna vaccines for main analysis, 42 and 90 days for sensitivity) and divided by the expected rate (incidence from published literature). Age-stratified rate ratios and 95% confidence interval (CI) were calculated.

In parallel, PMH was evaluated in an observational cohort study using US healthcare claims (HealthVerity) for women aged 45 - 75 years. Women receiving ≥ 1 dose of Spikevax bivalent (01SEP22 – 01MAY23) were compared to women receiving influenza vaccine and to women with medically-attended COVID-19. For each contrast, the incidence rate (IR) of PMH was reported and a propensity score (PS) was used for adjustment via inverse probability weighting. Hazard ratios (HR) and 95% CI, estimated via Cox proportional hazards regression, characterized the association between vaccination with Spikevax bivalent (vs influenza) and PMH.

Results: By October 2023, an estimated 1,025,499,641 Moderna COVID-19 vaccine doses had been administered worldwide. In the GSD, 978 PMH cases were identified; 113 were reported by health care professionals. Overall and age-stratified OE was substantially < 1 for all analyses performed.

Cohort analyses included 175,845 mRNA-1273.222 and 1,684,252 influenza vaccinated women aged 45-74 years. Demographic and clinical characteristics after PS weighting were similar between groups. The median onset of PMH was 78 days after vaccination. The weighted HR [95% CI] did not suggest an increased risk in any risk window assessed: 1-21 (0.72 [0.57, 0.90]), 1-42 (0.94 [0.81, 1.09]) and 1-90 days (0.97 [0.87,1.08]). Further, the IR of PMH was lower following Spikevax bivalent (IR 1.1, 95% CI 1.0-1.2 per 1,000 person-years) than following medically-attended COVID-19 (1.4, 95% CI 1.3-1.5 per 1,000 person-years).

Conclusions: Analyses showed no increased risk of PMH following Moderna’s SARS-CoV-2 vaccine. IR of PMH was higher following an episode of medically-attended COVID-19.