Covid-19 Vaccines and Menstrual Disorders: Reports from Sardinian Regional Centre of Pharmacovigilance: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: The anti-Covid vaccines approved in Italy are Comirnaty, Spikevax, Vaxzevria, Janssen, Nuvaxovid. As of March 26th, 2022, 134,361 adverse events following immunization have been collected in the National Pharmacovigilance Database, 69% of them concern women [1]. Regarding the Sardinian region, as of May 12th, 2022, there are 3043 total reports, 63.4% involve women. In July 2021, the French Drug Agency issued an alert about reports concerning menstrual alterations [2]. PRAC, since new studies have been published, recently decided to further investigate [3]. A cohort study conducted in the US comparing cycle length in a vaccinated cohort vs. an unvaccinated cohort, showed a statistically significant difference [4]. A British case-control study found that 20% of the population included reported menstrual changes, with a higher incidence in individuals with a history of Covid infection [5]. A Norwegian study showed similar results [6]. Objective: To describe the adverse events regarding menstrual disorders in the Sardinian population vaccinated against Covid-19. Methods: We analyzed reports of suspected adverse reactions in the National Pharmacovigilance Database regarding the region of Sardinia, from December 27th, 2020 to April 30th, 2022, we extracted those concerning menstrual cycle alterations after Covid-19 vaccine administration. Results: A total of 78 reports referring to all three scheduled administrations were collected. The majority concerned Comirnaty, with 56 reports 51 were non-serious, concerning abnormal menstrual cycles in lenght and flow, amenorrhea, dysmenorrhea;five cases were considered serious, but there were other adverse events associated (hypersensitivity reactions, autoimmune disorders, myocarditis in one case). Six reports were related to Vaxevria, with similar manifestations as for Comirnaty;in one case the patient was treated with Tamoxifen. Sixteen cases were reported for Spikevax, with one reporting an episode of bleeding in a three-year menopausal patient. In one case, the patient (IUD carrier) reported menstrual disturbances following all three vaccine administrations (two Comirnaty, one Spikevax). Conclusion: The different distribution of reports among the vaccines can be explained by the increased administration of Comirnaty in the general population and the phasing out of Vaxzevria. Menstrual disorders are common and can be related to several conditions, although a link with Covid vaccines is plausible, as highlighted by recent studies [4-6] and as already observed for other vaccines. In particular, the strong immune system response created by mRNA vaccines may affect the hypothalamic-pituitary-ovarian axis, which regulate the menstrual cycle.