Anti-COVID-19 Vaccination Alters the Menstrual Cycle and Dose Accumulation Enhances the Effect

Background and Objectives: New investigations have detected an enhanced probability for women to develop menstrual cycle alterations after anti-COVID-19 vaccination. Moreover, given that the protective immunity provided by anti-COVID-19 vaccination appears to wane quickly, booster vaccination has been recommended. Nonetheless, whether adverse events arise from such repeated immunization has not been studied. Materials and Methods: We studied the incidence of menstrual cycle alterations, the quantity of menstrual cycle alterations per subject, and of altered menstrual cycles in nonpregnant women of fertile age after anti-COVID-19 vaccination in a cohort of vaccinated female subjects by the means of a standardized questionary that was applied via telephone calls each month. Subjects that received up to four doses were studied for 6 months after each dose. We calculated the odds ratio for enhanced incidence, as well as quadratic functions for the tendencies. A sensitivity analysis excluding subjects taking hormonal birth control and those with polycystic ovary syndrome was performed. Results: Anti-COVID-19 vaccination enhanced the probability to develop menstrual cycle alterations (OR 1.52, CI at 95% 1.2-1.8, p < 0.0001) and, interestingly, such a tendency was enhanced when subjects received more doses (R² = 0.91). Furthermore, the same trends repeated for the quantity of alterations per subject, and of altered cycles. Such an effect was further demonstrated to be independent upon the vaccine brand being applied, the birth control status, and the diagnosis of polycystic ovary syndrome. Conclusions: Vaccination is the most cost-effective measure for primary prevention and is considered to be safe. Nonetheless, in this article, we show data that suggest that repeated vaccination of adult female subjects may lead to an enhanced incidence of menstrual cycle-related adverse events, quantity of alterations per subject, and altered cycles. We therefore think that the development of new vaccine formulations that produce longer-lasting immunity is of paramount importance to reduce the potential for dose accumulation-dependent enhanced risk.