Frequent Menstrual Disturbance Post-COVID-19 Vaccination in Otherwise Healthy Young Women of Reproductive Age Imply Stress and Vaccine Stimulations

The mechanism of menstrual-disturbance post-COVID-19 vaccination is subtle. Although direct interactions with molecular vaccines per se is reported, albeit the indirect stimulants, factors, patient demographics involved are not clear. Stress and uterine dysbiosis are largely overlooked despite the similar neurochemicals to that in the gut-brain-axis. Thus, more surveillance on women’s responses post-vaccination are needed. We aimed to survey the increasing trends in women’s menstrual disturbance post-pandemic vaccination for frequency, potential factors, patients’ demographics, and vaccine types involved using a self-administered web-based online public question-naire sent to different regions of Saudi Arabia. We collected data on 1372 women who developed menstrual ir-regularity after vaccination and used statistical analysis to examine and identify associated factors. In 1372 females; 61.1% (n=838) aged 19-29 years, 94.2% (n = 1292) Saudi citizens, 66.4% (n=911) graduates, 70% (n=965) were single, and only 15% (n=205) had chronic diseases. About 96.5% (n=1285) of 97% (n=1332) had two doses, mostly Pfizer's first and second doses (82% and 78, respectively) while ~3.5% (n=47) had one. No acute COVID infection appeared. The majority (77%; n=1057) reported no issues pre-vaccination except 23%(n=315) of whom 43% (n=135) reported worsening issues post-vaccination. However, 47.2% (n=629) complained only post-vaccination particularly after dose-2 (59% (n=370). These were mostly multiple simultaneously occurring issue in 75% (n=471) on cycle-timing disruptions the rest were low frequencies of decreased blood, missed periods, increased blood volume, pain, or increased bleeding. Potential reasons were fear, stress, mental health, and/or emotional problems in 51% (n=674), while 53% (n = 701) were worried about the pandemic. Although proportional differences between age-groups were significant (P =0.05), the relative frequency was highest in ages 30-39 (51%). Significant proportional differences in groups of (Pfizer, Moderna, Oxford, Don't know) occurred in outcomes post first (0.047) and second (0.049) doses. However, relative frequencies of outcomes were higher in Pfizer and Moderna. Logistic regression revealed postgraduate [OR=2.11 (0.98-4.72), P = 0.015) employment [OR=2.18 (0.95-4.86), P = 0.049]and Pfizer vaccine [OR = 2.09 (0.96-4.10), P= 0.029] two doses [OR=3.21(1.23-5.21), P = 0.030] as significant predictors. Mental health and emotional factors such as fear, worries, and emotional problems that triggered stress were also associated [OR=1.78 (0.76-3.21), P=0.033]. However, all other variables were not associated with menorrhea disturbances. Thus, menstrual disturbance was significantly associated with vaccina-tions. Fear, stress, mental health, worries about the pandemic, and/or emotional problems were the major reasons reported. Apart from direct viral interactions, these findings are consistent with the emerging evidence on indirect stress- and microbiome-induced stimulations. This is plausible in the absence of significant factors related to old-age, chronic diseases, and lifestyle-behaviors. These findings have significant implications in women’s health, gender-based interpretation, and vaccine improvement strategies. Future vertical studies on cortisol response and the consequence of uterine-dysbiosis in manipulating immune-response is warranted.