Association between Covishield vaccine and menstrual disturbance. Findings from a cross-sectional study among participants of Zero TB cohort in India

Abstract

Background: The association between covid-19 vaccine and menstrual disturbance is unclear.

Methods: An in-person cross-sectional survey among female members ≥ 18 years enrolled in an ongoing Zero TB prospective cohort in Northern India who had received one or two doses of covid-19 vaccine was conducted to study the characteristics and association of menstrual disturbance within six months of receiving Covishield.

Results: Between June 29 and September 5, 2021, 339 females ≥ 18 years of age were administered the survey. Median age was 30 (IQR: 22-39) years; 84 % were between 18 and 49 and 16 % were ≥ 50 years old. There were 152 college students, 27 healthcare workers, and 160 nuns. Forty-two women (12 %) had received one dose and 297 (88 %) had received two doses of Covishield. Overall, 66 (20 %) women reported experiencing menstrual disturbance after receiving Covishield vaccine. The problems included early menstruation: 6 % (n = 19/339); late menstruation: 4 % (n = 14/339); and heavier bleeding: 5 % (n = 17/339). Disturbances lasted for less than seven days and cycles normalized in 1-3 months. There was no post-menopausal bleeding. There was no significant difference in menstrual disturbance based on receiving one vs. two doses of Covishield (OR: 1.58; 95 % CI: 0.55-4.57; p = 0.381). History of SARS-CoV-2 infection was not associated with the development of menstrual disturbance among the vaccinees (OR: 0.63; 95 % CI: 0.24-1.73; p = 0.379). Presence of emotional disturbance at baseline (OR: 31; 95 % CI: 3.52-267; p = 0.002) or previous history of dysmenorrhea (OR: 41; 95 % CI: 8.7-196; p < 0.001) was associated with menstrual disturbance in the vaccinees, indicating their potential to confound or bias study results.

Conclusion: Menstrual problems were reported by Covishield vaccinees, but they were minor and reversible within three months and do not constitute a ground for vaccine hesitancy. Studies designed to assess causal link taking care to avoid selection bias or confounding are needed.

Keywords: Covid-19 vaccine; Menstrual disturbance; Women’s health.

Fig. 1.. Confounding in the assessment of causal relation between COVID-19 vaccines and menstrual disturbance

Individuals with comorbidities such as mental health conditions (e.g., depression, anxiety) may be at greater risk of developing menstrual disturbance. Simultaneously, individuals with mental health problems may be more or less likely to receive COVID-19 vaccines. In the case that such individuals are more likely to receive COVID-19 vaccines than those without mental health conditions, the effect estimate for the causal relation between COVID-19 vaccines and menstrual disturbance will be amplified, tending rightward away from the null. It has been shown that vaccination can reduce mental health problems on a community level and therefore, it is possible that individuals with mental health conditions may be more likely to receive COVID-19 vaccines. On the other hand, in the early phase of the pandemic, because of fear, uncertainty, and widespread mistrust, individuals with mental health conditions may have refrained from getting vaccines, which could reverse the association.

Fig. 2.. Selection bias in the assessment of the relationship between COVID-19 vaccines and menstrual health

*People with comorbidities such as pre-existing gynecological conditions, mental health problems, etc., are more likely to have received vaccines. A. In internet-based sampling strategies – which has been one of the most common sampling methods used for observational cohort studies that assess the risk of menstrual problems associated with COVID-19 vaccines – it is possible that the study sample may overrepresent individuals with comorbidities such as mental health problems (e.g., depression and anxiety) or pre-existing gynecological problems. These individuals, in turn, could be more likely to receive COVID-19 vaccines. Such individuals with comorbidities may also be at a greater risk of developing menstrual disturbance. Consequently, the effect estimate for the relationship between COVID-19 vaccines and menstrual disturbance will be amplified, tending rightward away from the null. Many investigations that insufficiently capture or report such comorbidities will still conveniently generalize to the larger population, causing serious damage to public health, such as by accentuating vaccine hesitancy. B. Many studies have administered cross-sectional surveys to assess whether vaccinated or unvaccinated individuals are more likely to have developed menstrual problems. However, the sampling technique employed by the studies is largely internet-based voluntary sampling. It is highly possible that individuals who had received vaccines and then developed menstrual problems would have volunteered to participate, whereas the unvaccinated population were not overrepresented for this outcome. Therefore, the vaccinated arm may be spuriously observed to have a higher risk of developing menstrual disturbance.