Postmenopausal bleeding after COVID-19 vaccination

Abstract

Background: There is a growing literature base regarding menstrual changes following COVID-19 vaccination among premenopausal people. However, relatively little is known about uterine bleeding in postmenopausal people following COVID-19 vaccination.

Objective: This study aimed to examine trends in incident postmenopausal bleeding diagnoses over time before and after COVID-19 vaccine introduction, and to describe cases of new-onset postmenopausal bleeding after COVID-19 vaccination.

Study design: For postmenopausal bleeding incidence calculations, monthly population-level cohorts consisted of female Kaiser Permanente Northwest members aged ≥45 years. Those diagnosed with incident postmenopausal bleeding in the electronic medical record were included in monthly numerators. Members with preexisting postmenopausal bleeding or abnormal uterine bleeding, or who were at increased risk of bleeding due to other health conditions, were excluded from monthly calculations. We used segmented regression analysis to estimate changes in the incidence of postmenopausal bleeding diagnoses from 2018 through 2021 in Kaiser Permanente Northwest members meeting the inclusion criteria, stratified by COVID-19 vaccination status in 2021. In addition, we identified all members with ≥1 COVID-19 vaccination between December 14, 2020 and August 14, 2021, who had an incident postmenopausal bleeding diagnosis within 60 days of vaccination. COVID-19 vaccination, diagnostic procedures, and presumed bleeding etiology were assessed through chart review and described. A temporal scan statistic was run on all cases without clear bleeding etiology.

Results: In a population of 75,530 to 82,693 individuals per month, there was no statistically significant difference in the rate of incident postmenopausal bleeding diagnoses before and after COVID-19 vaccine introduction (P=.59). A total of 104 individuals had incident postmenopausal bleeding diagnosed within 60 days following COVID-19 vaccination; 76% of cases (79/104) were confirmed as postvaccination postmenopausal bleeding after chart review. Median time from vaccination to bleeding onset was 21 days (range: 2-54 days). Among the 56 postmenopausal bleeding cases with a provider-attributed etiology, the common causes of bleeding were uterine or cervical lesions (50% [28/56]), hormone replacement therapy (13% [7/56]), and proliferative endometrium (13% [7/56]). Among the 23 cases without a clear etiology, there was no statistically significant clustering of postmenopausal bleeding onset following vaccination.

Conclusion: Within this integrated health system, introduction of COVID-19 vaccines was not associated with an increase in incident postmenopausal bleeding diagnoses. Diagnosis of postmenopausal bleeding in the 60 days following receipt of a COVID-19 vaccination was rare.

Keywords: COVID-19 vaccination; incidence rates; postmenopausal bleeding; segmented regression; temporal scan statistic; uterine bleeding; vaccine adverse events.

Figure 1.

Monthly incidence of postmenopausal bleeding between January 2018 and December 2021 among female patients 45 years of age and older at Kaiser Permanente Northwest Legend: The solid line represents overall monthly incidence of postmenopausal bleeding diagnoses among females ages ≥45 years within the Kaiser Permanente Northwest health system over the study period; the shaded areas represent the upper and lower 95% confidence intervals. Period 1 = pre-SARS-CoV-2 (January 2018 through January 2020), Period 2 = SARS-CoV-2 and pre-COVID-19 vaccine availability (February 2020 through November 2020), and Period 3 = post-COVID-19 vaccine availability (December 2020 through December 2021).

Figure 2.

STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) flow diagram from Kaiser Permanente Northwest electronic medical record data Legend: Data span December 14, 2020, through August 14, 2021, for the underlying population and December 14, 2020, through October 14, 2021, for individuals with post-COVID-19-vaccination PMB codes.

Figure 3.

Postmenopausal bleeding diagnostic procedures and findings among chart-confirmed, postmenopausal bleeding cases with onset in the 60 days following a COVID-19 vaccine (n=79) Legend: Cases identified within the Kaiser Permanente Northwest health system from December 14, 2020, through October 14, 2021. Ninety-six percent of patients had an endometrial/cervical biopsy or a transvaginal ultrasound, and 57% had both procedures.

Figure 4.

Postmenopausal bleeding etiology documented in medical record among chart-confirmed, postmenopausal bleeding cases with onset in the 60 days following a COVID-19 vaccine (n=79) Legend: Cases identified within the Kaiser Permanente Northwest health system from December 14, 2020 through October 14, 2021. Five patients had two contributory causes of bleeding: three were diagnosed with endometrial hyperplasia and a uterine or cervical lesion, one with a uterine or cervical lesion and uterovaginal prolapse, and one with proliferative endometrium and hormone-therapy-related bleeding. Two patients (4%) were found to have a malignancy.

Figure 5.

Timing of bleeding onset in the 60 days following a COVID-19 vaccine among chart-confirmed, postmenopausal bleeding cases without a clinical etiology for the bleeding (n=23) Legend: The X-axis displays the number of postmenopausal bleeding diagnoses on each day within the 60-day window following receipt of a COVID-19 vaccine, administered between December 14, 2020, and August 14, 2021. Day zero represents the date of COVID-19 vaccine receipt and was excluded. The scan statistic identified one cluster of bleeding onset at days 11 and 12 post-vaccination, however it was not statistically significant (p=0.63).