COVID-19 vaccine side effects on menstrual disturbances among Iranian women.

Findings about participant's age summarized in chart 1. As this data around 2/3 of participants have more than 30 years old ( Fig. 1 ) (see Fig. 2 ). Fig. 1 Percentage of participant's age that received Covid-19 vaccines. Fig. 1 Fig. 2 Percentage of different types of vaccine that received by precipitants in first (A), second (B) and third (C)doses. Fig. 2 Percentage of participant's age that received Covid-19 vaccines. Percentage of different types of vaccine that received by precipitants in first (A), second (B) and third (C)doses. Most of precipitants (>60%) don't have any menstrual disorders after vaccination, but 18.4% of persons have menstrual disturbance after receiving first dose of vaccine, and 20.9% after second dose, 12.5% following third dose and 0.2% after all three doses ( Fig. 3 ). Fig. 3 Percentage of peoples that have menstrual disorders after vaccination (three doses). Fig. 3 Percentage of peoples that have menstrual disorders after vaccination (three doses). Relative risks of menstrual disorders shown in Fig. 4 in women that have menstrual period. More than 50% don’ have any symptoms after vaccination. Latency of menstruation is more than other disturbances (19.4%), then premature menstruation (17.1%). Some of precipitants reported that have more than 1 above symptoms (data not shown) ( Fig. 4 ). Fig. 4 Side effects self-reported to the COVID menstrual symptom study after COVID-19 vaccination in menstrual women. Fig. 4 Side effects self-reported to the COVID menstrual symptom study after COVID-19 vaccination in menstrual women. The women that are in menopausal age more than 85% don't have any problem ( Fig. 5 ), although around 7% mentioned to their history of endometriosis, ovarian cyst and …. That we didn't exclude them. Fig. 5 Side effects self-reported to the COVID menstrual symptom study after COVID-19 vaccination in menopausal women. Fig. 5 Side effects self-reported to the COVID menstrual symptom study after COVID-19 vaccination in menopausal women. Relative risks of menstrual disorders after AstraZeneca vaccine are around 40.9%, Sinopharm 50.6%, Sputnik 38%, Barkat 33% and Baharat 66% in all doses (data not shown).

Data were collected from an online anonymous survey conducted from 1Jan to 1 th April 2022. This cross-sectional study included a convenience sample of Iranian women. We used Google Forms, an online survey platform, to publish the questionnaire, and the link generated was then shared via social networks such as, Email, Instagram, Telegram and WhatsApp. The interviewees visited the URL on their electronic devices to answer the questionnaire. The inclusion criteria were individuals who [ 1 ] were 16 years old until more than 55 [ 2 ], voluntarily agreed to participate in the online survey and [ 3 ] were able to read and complete the self-administered questionnaire independently. After excluding those participants who have some gynecological disorders such as Uterus fibrosis, Endometriosis, ovarian cysts or taking hormonal medications (n = 39), a total of 455 participants were finally included in the present study. The participants had received some types of vaccines in Iran. The type of vaccine includes Sinopharm, AstraZeneca, Sputnik, Baharat, Barkat. The study questionnaire was divided into three main sections. The first section was designed to collect information about the participant's age. The second section focused on type to vaccinate against COVID-19. The third section focused on the COVID-19 vaccine possible side effects experienced after the first, the second and third one on menstrual disorders such as Premature menstruation, latency of Menstruation, Heavy bleeding, Spot bleeding, Increase the number of menstrual days, decrease the number of menstrual days, Dysmenorrhea in menstrual or menopausal ages. We calculated the prevalence of unusual menstrual symptoms after vaccine dose one, two and three respectively. For the main analysis, we used a self-controlled case series (SCCS) design. Vaccinated cases with the outcome in question were included in the data set. For descriptive analyses, numbers and percentage were used to detail sample characteristics. Percentages and chi-square tests were used to evaluate the associations between vaccination and possible side effects.

The present study aimed to study the association between possible side effects after receiving COVID-19 vaccine and menstrual disorders. We found a higher risk of some side effects against COVID-19 vaccine. These results are in agreement with previous works that reported. In a UK survey including almost 5000 vaccinated women, 8 menstrual disturbance was reported by 20% of individuals after vaccination [ 7 ]. In a recent preprint of a US web-based survey recruiting only vaccinated participants through Twitter and other social media platforms, 42% of people with regular menstrual cycles bled more heavily than usual, while 44% reported no change, after being vaccinated [ 8 ]. In a smaller Saudi-Arabian web-based survey on side-effects after COVID-19 vaccination Menstrual disturbances were reported in this open text field, and only a small proportion of the respondents reported abnormal menstrual cycle (delaying/increase hemorrhages or pain): 0.98% of Pfizer BioNTech and 0.68% (7/1028) of ChAdOx1 vaccinees [ 9 ]. Menstrual irregularities after both the first and second doses of the vaccine were found to self-resolve in approximately half the cases within two months [ 10 , 11 ]. Issakov et al. reported the most generally described menstrual disturbance was bleeding [ 12 ] but our results shown latency or premature menstruation. These differences may be because of vaccine types and life style in different countries. Many women across the world after receiving COVID vaccines are repining of irregularities in their menstrual bleeding; some experiencing heavy menstrual bleeding (menorrhagia), some bleeding before their periods were due or bleeding frequently (metrorrhagia/polymenorrhagia), whereas some are complaining of postmenopausal bleeding [ 6 , 13 ]. By comparing the six vaccine types in 6 Arabic countries, a higher percentage of menstrual irregularity was observed in Johnson & Johnson, followed by Sinopharm, Moderna, and AstraZeneca. Similarly, Johnson & Johnson was associated with a higher percentage of heavy bleeding with coagulations, followed by Pfizer, Sinopharm, AstraZeneca, and Moderna [ 11 ]. In our study latency of menstruation is more than other disturbances, also some of precipitants suffered from more than complication such as latency plus heavy bleeding or premature and spot bleeding together. Lill Trogstad et al. reported the prevalence of unusually heavy bleeding was higher than other [ 14 ]. Previously some studies reported people who were irregular and long menstrual cycles have been associated with a greater risk of premature mortality, and infrequent or absent menstruation can be an indicator of reduced fertility [ 15 ]. Following vaccination for COVID-19, menstrual disturbance occurred in 20% of individuals in a UK sample [ 7 ]. It is suggested that be a connectivity between immune response and vaccination rather than a specific vaccine component. Vaccination against human papillomavirus (HPV) has also been associated with menstrual changes [ 16 ]. The menstrual cycle can be affected by immune activation in response to different stimuli, including viral infection [ 17 ]. Biologically possible mechanisms linking immune stimulation with menstrual changes and hormones driving the menstrual cycle or effects mediated by immune cells in uterus endometrium, which are involved in the cyclical build-up and breakdown of this tissue [ 18 ]. Hypothalamic– pituitary–gonadal axis is sensitive to inadequate sleep, physical and psychological stress. Pulsatile mechanism of hormones is essential for regular menstrual cycle. Therefore, disruption of regularity in hormone release may cause to menstrual disorders [ 6 ]. Vaccination may shorten or lengthen the menstrual cycle by influencing the secretion and stability of estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction [ 19 ]. Our study has a number of limitations; first of all, a potential limitation of vaccination in IRAN, limitans access to different types of vaccines, convenience sampling of the study participants regarding the generalizability of the results, the online nature of the data collection, life style, culture and religion of Iranian people.

We found a relation between side effects of the COVID-19 vaccine and menstrual changes. Although menstrual disturbances are not a contraindication for vaccination, but if the link between vaccination and menstrual changes will confirmed with more studies, who rely on being able to guess their menstrual cycles to either achieve or avoid pregnancy. Information about menstrual changes should be require in future clinical trials, including trials of covid-19 vaccines. Recent informal reports of menstrual changes after vaccination for COVID-19 may have given rise to vaccine doubt or baulk.

COVID-19 viral infection was affected all the world from Dec 2019. This new corona virus causes different health problems in human's body systems mainly Respiratory system like pneumonia, acute respiratory distress syndrome (ARDS), Sore throat and sometimes kidney injury, myocardial dysfunction, and gastrointestinal diseases [ 1 ]. From the beginning of disease World Health Organization (WHO) offers wearing masks, cleaning hands, ensuring good ventilation indoors, physical and social distancing, avoiding crowd and then safe and efficient vaccines to end COVID-19 [ 1 ]. Several months no study investigated the prevalence of adverse side effects of the vaccines and all studies reported vaccines to be highly effective [ 2 ]. Common side effects of covid-19 vaccination listed by the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) [ 3 ]. Pain, redness, swelling, tiredness, headache, muscle pain, chills, fever nausea are accepted as side effects of vaccines. However, menstrual cycle regularities were studied rarely [ 1 ]. Many factors, including nutrition, sleep, and exercise, as well as illness, travel, and stress, are known to influence the length of the menstrual cycle [ 4 ]. Primary care clinicians in reproductive health reported different changes to periods and bleeding after vaccination [ 3 ]. Menstrual changes have been reported after both mRNA and adenovirus vectored covid-19 vaccines, suggesting that is likely to be a result of the immune response to vaccination rather than a specific vaccine component. The menstrual cycle can be affected by immune activation in response to various stimuli, including viral infection or vaccination [ 5 ]. After vaccination, some women complained of menstrual irregularities and changes such as heavy menstrual bleeding (menorrhagia), frequent bleeding (metrorrhagia/polymenorrhagia), altered menstrual duration, postmenopausal bleeding and volume (heavier bleeding and clotting), increased dysmenorrhea and worsened premenstrual syndrome [ 6 ]. Menstrual changes have been reported previously after mRNA and adenovirus vectored covid-19 vaccines, but not about inactivated or dead virus-based vaccines. Thus, in this study we investigated different types of Covid-19 vaccines effects on menstrual disorders in Iranian women.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.