The Effect of COVID-19 Infections and Vaccination on Menstrual Cycle Symptoms in the South of Jordan: A Cross-sectional Study

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Methods : A cross-sectional survey utilizing face-to-face interviews from 1 October to 31 December 2021 was conducted in the city of Kerak in the southern part of Jordan. The study questionnaire assessed the impact of COVID-19 infection and vaccines on menstrual symptoms. It included sociodemographic characteristics, medical and reproductive history, the contraceptive method, MC status, previous medical and drug history, and the effect of infection and vaccination on the MC. Results: This study questionnaire was completed by 400 participants with a mean age of 32.1±12.6. Regarding the history of COVID-19 infections, 33.8% of the participants reported a history of confirmed COVID-19 infections. 77.8% of them do not report any menstrual changes following the infection, while the remaining 22.2% reported changes in menstruation. The most commonly reported post-COVID-19 symptoms were irregular MC (27.6%) and light MC (24.15) or dysmenorrhea (24.1%). Heavy menstruation was reported by 17.2% of participants post-COVID-19 infection. Two-thirds of study participants (66.6%) reported no changes in the MC following the COVID-19 vaccine. The most reported symptoms for those who experienced changes in the MC following the vaccination were irregular MC (13.1%), heavy menstruation (7%), and light menstruation (7%). Other reported symptoms were: dysmenorrhea (4.6%), intermenstrual bleeding (1.2%), and amenorrhoea (0.5%). Conclusion: This is the first published study from Jordan on the impact of COVID-19 infection and vaccine on menstrual symptoms. It revealed minor changes in the MC following COVID-19 infections and the COVID-19 vaccine. These findings are consistent with published reports. It is recommended that future clinical trials for new vaccines for women within childbearing age to include outcomes related to sex hormones and MC. Women should be encouraged to take the vaccines and to report symptoms for healthcare professionals for further assessment. Jordan COVID-19 Menstrual cycle COVID-19 vaccine Figures Figure 1 Figure 2 Introduction Menstrual cycle (MC) is a regular sloughing of the uterine lining regulated by hormones released from hypothalamic-pituitary-gonadal axis ( 1 ). The length of the MC is the time between the menstrual bleeding and the onset of bleeding of the next cycle ( 2 ). The normal duration of MC is between 25–30 days with duration less than 21 days is known as polymenorrhagia and greater than 35 days is termed Oligomenorrhea ( 2 ). The typical volume of the lost blood during the MC is about 30 ml with volumes greater than 80 ml is considered abnormal ( 2 ). Globally, 5–34% of MC are irregular during the childbearing age ( 3 , 4 ). Different stressors implicated in the deregulating the MC including certain medications, certain viral infections, structural abnormalities, obesity, sudden weight loss, smoking, and psychological problem ( 5 , 6 ). Certain viral infectons as Coronavirus (CoV) has been added as an exceptional stressor affecting MC regardless that the individuals have been infected or not ( 7 ). Historically, the discovery of CoV was in 1960s. Since that, the international committees specialized in viral taxonomy have been working to classify CoV at different cluster levels ( 8 ). In the past, the two most sever types of CoV associated pandemic are the severe acute respiratory syndrome coronavirus 2 (SARS) (in 2002–2003) and Middle East respiratory syndrome (MERS) in 2012 ( 8 ). CoV is a zoonotic disease and transmitted through contact and droplet mechanisms ( 9 ). In December 2019, the first case of Coronavirus disease 2019 (COVID-19) was identified in Wuhan, China resulting in the COVID-19 pandemic. COVID-19 is the causative agent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ( 8 ). COVID-19 associated disorders range from mild to fatal ones ( 10 , 11 ). By the time of writing this manuscript, COVID-19 cases in Jordan have reached 1,746,997 with 14,122 deaths while globally the number of cases have reached 676,206,330 with 6,771,699 deaths ( 12 , 13 ). In addition to the administration vaccination as a main control of COVID-19, different treatment regimens have been prescribed to treat COVID-19 patients. One important group of drug are Statins that act by lowering the circulatory cholesterol which eventually ameliorates the vascular endothelial function ( 14 , 15 ). Different vaccination predicators have been found to play an important role in the adherence of people to the vaccination programs including age, socioeconomic status, education and health literacy ( 15 ). Moreover, the trust in the health environment through proper broadcasting of health information plays an important role in linking people’s information reception and vaccination intention ( 16 ). MC disorders have a substantial negative impact on quality of life and a huge socioeconomic burden for women and the health services ( 17 , 18 ). Unfortunately, the COVID-19 studies particularly vaccine trials excluded its effect on the menstruation in the context of how many women have shown MC disorders, how long these persisted, and the impact of these disorders ( 17 ). The COVID-19 vaccination program in Jordan started early in January 2020. The most common rerecorded side effects (SE) of these vaccines among Jordanian people including pain, swelling and redness at the site if injection, fatigue, chills, fever, myalgias, headache, and nausea ( 19 ). One the possible side effect that needs further investigations is the effect of the vaccine on the female MC. The impact of COVID-19 vaccine on the reproductive system is still not studied thoroughly. It has been shown that the COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor ( 20 ). This receptor is highly expressed in the female reproductive system including the uterus ( 21 ). The binding of the COVID-19 to the ACE2 receptor in the endometrium may be associated with the deregulation of the MC ( 22 ). After vaccination, a percentage of women experienced menstrual irregularities such as heavy menstrual bleeding (menorrhagia), frequent bleeding (metrorrhagia/ polymenorrhea), or postmenopausal bleeding ( 23 , 24 ). Recently, studies emphasized the relationship between COVID-19 infection and menstrual disturbances ( 25 ). There have been limited number of published studies on the impact of COVID-19 vaccine and COVID-19 infections on the menstrual symptoms. Published studies have reported ranges of MC disturbances following COVID-19 vaccination ( 26 – 30 ). The thousands of self-reported MC related issues were sent to the United States Vaccine Adverse Event Reporting System (VAERS). The United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) yellow card surveillance scheme gives a strong relation between MCs changes following COVID-19 vaccination ( 26 ). In Jordan, studies have shown that COVID-19 infection could affect the MC ( 31 , 32 ). Moreover, it was reported that the timing of MC was alerted after vaccination among Jordanian females. It was concluded by another report from Jordan that the impact of COVID-19 vaccine on the reproductive system among Jordanian females needs further research ( 33 ). We, therefore, conducted a prospective cross-sectional study to investigate the impact of COVID-19 infections and vaccines on menstrual symptoms locally. Methodology Data collection This was a cross-sectional survey utilizing face-to-face interviews from January first to 31 March 2022. According to national statistics, it is estimated that 51.519 females aged 15 to 50 in Karak governorate. A sample size of 382 is needed with a margin of error of 0.05 ( 34 ). The selected sample was 400 Jordanian females from the general population. We followed a multistage sampling technique from the general population through door to door approach by research coordinators. The study was conducted at the Karak governorate in the south of Jordan. We collected the study from different socioeconomics areas in Karak governorate from the city and two villages. Permission was approved before carrying on this study from the ethics committee in the faculty of medicine at Mutah University under the approval number 1002020. Our research assistants started to complete the questionnaires after having a verbal consent from all volunteers. All questionnaires were completed without including the names or other identifier to maintain confidentiality. Measures A questionnaire consisted of fifteen questions was developed in English language by a group of experts in the field and based on the literature related to the topic of this research ( 35 – 37 ). Questionnaire was divided into three sections; the first section addressed the sociodemographic and medical history of the participants. The second section covered COVID-19 infections and vaccinations while the third section covered menstrual symptoms. Questionnaire was piloted on 30 participants and modified accordingly. Pilot data was not included in the final analysis. The participants were asked about their background characteristics, including the age, marital status, and if married they were asked about the parity and the number of abortions. The married participants asked the question regarding their contraceptive methods they are using including none, natural method (Breast feeding, coitus interruptus), oral contraception, intrauterine contraceptive device, implant, and injectable progesterone. Their age of participants' menarche was included in the questionnaire. An important question indicating their MC status including regular (21–35 days, 3–8 days length, average bleeding, primary dysmenorrhea), regular (21–35 days, 3–8 days length, average bleeding, no dysmenorrhea), irregular (< 21 days or 35 days), and if they are menopause. The previous medical history was also considered if they are medically free, diabetes, hypertension, thyroid disorders, polycystic ovarian syndrome, and endometriosis. Drug administration history on the use of anticoagulants (aspirin or heparin) and thyroxin was addressed in the questionnaire as these drugs known to affect the duration of menstrual following the gynecologist recommendations. Wether the participants had a history of COVID-19 infection or not was also listed in the questions. The symptoms that the participants experienced during the period after the infection and during the period after receiving the vaccine including heavy MC, intermenstrual bleeding, irregular MC, amenorrhea, dysmenorrhea, light MC, post-menopausal bleeding, and no symptoms at all. The kind of vaccine and the number of doses were also included among the questions. The date when the participants received the vaccine was mentioned and included the intervals between less one month to more than four months ago. Participants history of visiting a gynecologist for MC related complaint was included in the questioner as well. Inclusion and exclusion criteria The inclusion criteria were: Jordanian females reside in the selected area for at least 2 years, and having regular MCs for at least one-year prior the administration of the COVID-19 vaccination. On the other hand, the exclusion criteria included females had prior history of amenorrhea, bleeding disorders, female underwent abdominal or pelvic surgery, taking any medications that interfere with the normal MC, breastfeeding women, and diagnosis with medical condition that could influence cycle regularity, such as endometriosis, polycystic ovarian syndrome, and thyroid disorders. Data analysis The numbers obtained were expressed as percentages or as mean ± SD. The results were interpreted after tabularizing them in frequencies and percentages. All calculations were carried out using the Statistical Package for the Social Science (SPSS); SPSS Inc., Chicago, IL, USA) version 20.0 for Microsoft Windows. The dependent variable is the symptoms during the period after the infection, while the remaining variables were considered independent (Table 1 ). Independent variables were history of covid-19 infection and type of COVID-19 vaccine. Menstrual symptoms were the dependent variable. We had no issues with missing data as all interviews were done in a face to face manner. Results The study questionnaire was completed by 400 participants with mean age of 32.1 ± 12.6. The average parity was 4 ± 2.5 and abortion 0.8 ± 1.6. The mean age at menarche is 13.4 ± 1.4. As shown in Table 1 , half of the study participants were singles. Two third of the participants reported that they never used any sort of contraception, while 16.5% of the participants used the natural method of avoidance of fertility days. On the other hand, hormonal contraceptive methods and intrauterine contraceptive device (IUCDs) were followed by 9.8% and 9.3% of the participants respectively. Menstruation status prior to COVID-19 infections and vaccines, showed a high rate of regular menstruation with primary dysmenorrhea (64%). The 14 Participants, who reported that they were on anticoagulants, were excluded from the analysis. Regarding history of COVID-19 infections, 33.8% of the participants reported history of confirmed COVID-19 infections. 77.8% of them do not report any menstrual changes following the infection, while the remaining 22.2% reported changes in menstruation. Figure 1 shows a comparison in menstrual symptoms between participants with a history of COVID-19 and those without a history of COVID-19 infection. There was no statistically significant difference between these two groups. This figure shows that the most commonly reported post-COVID-19 symptoms were irregular MC (27.6%) and light MC (24.15) or dysmenorrhea (24.1%). Heavy menstruation was reported by 17.2% of participants post-COVID-19 infection. Table 1 Background information of study participants (n = 400) Attribute Category Type Frequency Proportion (%) Marital Status Single Independent 213 51.4 Married 189 45.7 Divorced/Widow 12 2.9 Contraception method used Hormonal Independent 19 9.8 IUCDs 18 9.3 Natural Method 32 16.5 None 125 64.4 Menstruation status Irregular Independent 43 10.4 Menopause 38 9.2 Regular no primary dysmenorrhea 68 16.4 Regular primary dysmenorrhea 265 64.0 Medical history History of chronic diseases Independent 66 16.0 Medically free 347 84.0 Use of Anticoagulants No Independent 400 96.6 Yes 14 3.4 History of Covid-19 Infection Yes, I got the infection Independent 126 30.4 No, I did not get infected by the virus 288 69.6 Symptoms during the period after the infection (29 participants) None Dependent 99 77.3 Heavy MC 5 3.9 Intermenstrual bleeding 1 17.2% Irregular MC 8 3.4% Dysmenorrhea 7 27.6% Light MC 7 24.1% Post-menopausal bleeding 1 24.1% covid-19 vaccine type Pfizer Independent 244 58.9 Astrazeneca 7 1.7 Sinopharm 162 39.1 Sputnik 1 0.2 IUCDs: intrauterine contraceptive devices Menstrual symptoms post COVID-19 vaccine: All study participants reported that they have received at least one dose of COVID-19 vaccine. Majority of them (88.2%) received two doses, while 3 participants only (0.7%) received three doses. The remaining 46 participants (11.1%) received only a single dose of vaccine. Most of the study participants received either Pfizer mRNA Vaccine (58.9%) or the inactivated Sinopharm vaccine (39.1%). Two thirds of study participants (66.6%) reported no changes in the MC following COVID-19 vaccine. The most reported symptoms for those who experienced changes in the MC following the vaccination were irregular MC (13.1%), heavy menstruation (7%), light menstruation (7%). Other reported symptoms were: dysmenorrhea (4.6%), intermenstrual bleeding (1.2%), and amenorrhoea (0.5%). Only ten participants sought medical advice from a gynecologist for these symptoms. Outcomes of assessment were abnormal hormonal profile and normal ultrasound for three participants, while two participants had abnormal ultrasound and normal hormonal profile. The remaining five participants had a normal hormonal profile and normal ultrasound. Figure 2 shows a comparison in menstrual symptoms by type of vaccine received by study participants. There was no statistically significant difference between the three groups. The main difference between them is that participants who received other vaccines (other than Pfizer or Sinopharm) did not report irregular MC or light menstruation post-vaccination. Finally, Table 2 shows a comparison between Sinopharm and Pfizer vaccines in terms of reported symptoms post-vaccination. Overall, more symptoms were reported post-Pfizer vaccine when compared with the Sinopharm vaccine. Amenorrhea and intermenstrual bleeding were reported by two and five participants who received the Pfizer vaccine. On the other hand, these two symptoms were not reported by participants who received the Sinopharm vaccine. Table 2 Comparison in the proportion of self-reported menstrual changes between Sinopharm and Pfizer COVID-19 vaccines Symptoms Sinopharm Pfizer P-value Frequency Proportion Frequency Proportion Irregular MC 16 10.3 36 15.1 0.222 Light MC 13 8.4 15 6.3 0.5589 Heavy MC 10 6.5 18 7.6 0.8274 Dysmenorrhea 6 3.9 13 5.5 0.6326 Intermenstrual bleeding 0 0 5 2.1 0.1752 Amenorrhea 0 0 2 0.8 0.6753 Post-menopausal bleeding 0 0 0 0 Discussion Several recent studies and reports have highlighted the need for more evaluation of the impact of COVID-19 infections and vaccines on the reproductive system and menstruation. Published data so far are not robust enough to draw a firm conclusion. We conducted a local study in Jordan on women within reproductive age group from general population. Our findings revealed an overall mild change in the menstrual symptoms due to COVID-19 infections or vaccines. All participants received COVID-19 vaccines; most received at least two doses. Pfizer and Sinopharm vaccines were the most widely received vaccines. Post-vaccination menstrual changes were also mild with no statistically significant differences between vaccines. Three quarters of our sample did not report any menstrual changes following COVID-19 infection. The most common reported menstrual symptoms for women, who experienced changes in the MC, were irregular MC, light MC, and dysmenorrhea. Heavy menstruation was reported by small proportion of the study participants. Our results are consistent with the finding of a recent systematic review. This systematic search was conducted on the Medline, Scopus, and Cochrane Library databases to assess the impact of COVID-19 infection on MC. Only three studies were included in the final analysis. Results of this review revealed that SARS-CoV-2 led to menstrual irregularity with decreased menstrual volume and prolonged cycle as the commonest two reported symptoms ( 38 ). Another study from Ireland included 1031 women of reproductive age who completed an anonymous digital survey as part of an observational study of women’s reproductive health over the course of the pandemic ( 37 ). Around half of the participants (46%) reported a change in their MCs since the beginning of the pandemic. This study revealed significant changes in the MC when compared with the pre-pandemic period. Participants reported significantly more menorrhagia, dysmenorrhea, and a worsening of premenstrual symptoms than before the pandemic. However, this study did not report the proportion of participant who had confirmed COVID-19 infections, and, therefore, the stress level, as described below, could play a major role in the reported symptoms. Another study from China showed consistent results with our findings ( 25 ). This study evaluated the effects of COVID-19 infection on the sex hormones and menstrual changes among women with confirmed COVID-19 infection. This study revealed that approximately 20% of the patients had a significant decrease in menstrual volume, without a significant difference by disease severity. Approximately 20% of COVID-19 patients showed prolonged MCs. A smaller proportion of participants reported an increase in menstrual volume and/or MC shortening. Similar finding were reported from Arizona, USA with 16% (n = 20) of the participants reported MC changes following COVID-19 infection ( 39 ). Changes in the menstrual symptoms could be related to the viral infection with SARS-CoV-2 or due to the changes in the stress level associated with the infection state ( 40 ). Infection with SARS-CoV2 affects the immune system and causes an increase in interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) and other cytokines. This is in addition to the potential alteration on hypothalamic– pituitary–gonadal axis due to this infection ( 41 – 44 ). High stress levels due to the infection or the pandemic worldwide are associated with menstrual irregularities COVID-19 pandemic has changed life worldwide. It has been associated with different stressors such as losing loved ones, losing jobs, and health changes due to the infection ( 45 ). A recent study has revealed a significant prolongation of menses and heavier menstruation among participants with a high perceived stress scale (PSS) compared to those with a moderate COVID-19 PSS ( 46 ). Similar to our findings, a range of MC changes after COVID-19 vaccination have been reported in several studies, including longer and shorter cycles, missed cycles, heavier and lighter menstrual flow, and intermenstrual spotting ( 47 – 49 ). The main limitation of the scientific evidence related to COVID-19 vaccines impact on reproductive health is that clinical trials of covid-19 vaccines did not include menstrual changes within their outcomes. The impact of COVID-19 vaccines on MC were assessed in our study based on participants’ own reporting. Two thirds of study participants reported no changes in the MC following COVID-19 vaccine. The most reported symptoms for those who experienced changes in the MC following the vaccination were irregular MC, heavy menstruation, and light menstruation. Our results are consistent with international reports and published studies. A US only cohort provides further evidence of small cycle length changes associated with covid-19 vaccination and support our findings ( 50 ). A recently published study from Italy revealed that 50 to 60% of reproductive-age women experienced MC irregularities, regardless of the type of the received COVID-19 vaccine. The incidence of the symptoms was a slightly higher (60–70%) following the second dose of the vaccine. The most common reported changes were shorter MCs, longer cycles, and heavier menstruation than was expected and usual ( 51 ). Difference in results between our study from Jordan and this Italian study is that around 40% of our sample received the inactivated Sinopharm vaccine. While the Italian study population mainly received mRNA vaccines. This could justify difference in the proportion of reported symptoms. An important cohort study from the USA showed the resolution of menstrual changes in the cycle post vaccine. This study also revealed that the cycle length changes associated with mRNA vaccines do not appear to differ from those with other vaccine mechanisms. These finding reassure women about the reversibility of menstrual changes post COVID-19 vaccines ( 26 ). The strength points of this study are the prospective data collection regarding the MC which limits the bias associated with memorizing MC features among participants and the face to face method of data collection which was helpful to identify the small clinical difference in the MC that might be missed by the participants. The main limitation of our study lies in the differences in intervals post-vaccination between study participants. Additionally, it is based on self-reported changes post-COVID vaccines through retrospective approach subjecting the findings to recall bias. However, our analysis results are consistent with published studies on the impact of COVID-19 infection and vaccines. This is the first published study from Jordan on the impact of COVID-19 infection and vaccine on menstrual symptoms. It revealed minor changes in the MC. It is recommended that future clinical trials for new vaccines for women within childbearing age to include outcomes related to sex hormones and MC. Women should be encouraged to take the vaccines and to report symptoms to healthcare professionals for further assessment. Declarations Ethics approval and consent to participate Ethical approval to conduct the present study was obtained from the ethics committee of the Faculty of Medicine, University of Mutah under the permission number 1002020. All procedures were performed in accordance with the ethical standards of the institutional and/or national research committees and the Declaration of Helsinki and its later amendments, or comparable ethical standards. Availability of data and materials All datasets generated or analyzed during this study are included in the manuscript. Competing interests The authors declared that they have no competing interest. Funding This work was not financially supported by any organization. Authors' contributions All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. 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The psychoneuroendocrinology of functional hypothalamic amenorrhea. Psychiatric Clinics of North America. 1989;12(1):105-16. Giles DE, Berga SL. Cognitive and psychiatric correlates of functional hypothalamic amenorrhea: a controlled comparison. Fertility and sterility. 1993;60(3):486-92. Berga SL, Loucks TL. Use of cognitive behavior therapy for functional hypothalamic amenorrhea. Annals of the New York Academy of Sciences. 2006;1092(1):114-29. Nagma S, Kapoor G, Bharti R, Batra A, Batra A, Aggarwal A, et al. To evaluate the effect of perceived stress on menstrual function. Journal of clinical and diagnostic research: JCDR. 2015;9(3):QC01. Ozimek N, Velez K, Anvari H, Butler L, Goldman KN, Woitowich NC. Impact of stress on menstrual cyclicity during the coronavirus disease 2019 pandemic: a survey study. Journal of Women's Health. 2022;31(1):84-90. Alvergne A, Kountourides G, Argentieri A, Agyen L, Rogers N, Knight D, et al. COVID-19 vaccination and menstrual cycle changes: A United Kingdom (UK) retrospective case-control study. MedRXiv. 2021. Male V. Menstrual changes after covid-19 vaccination. British Medical Journal Publishing Group; 2021. Trogstad L. Increased occurrence of menstrual disturbances in 18-to 30-year-old women after COVID-19 vaccination. Available at SSRN 3998180. 2022. Cohort A. Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination. Obstet Gynecol. 2022;139:1-9. Laganà AS, Veronesi G, Ghezzi F, Ferrario MM, Cromi A, Bizzarri M, et al. Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey. Open Medicine. 2022;17(1):475-84. Cite Share Download PDF Status: Published Journal Publication published 10 Apr, 2024 Read the published version in Journal of the Egyptian Public Health Association → Version 1 posted Editorial decision: Major revision 21 Oct, 2023 Reviewers agreed at journal 27 Sep, 2023 Reviewers invited by journal 25 Aug, 2023 Editor assigned by journal 20 Aug, 2023 First submitted to journal 17 Aug, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3273125","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":228829332,"identity":"9e256d8d-6ed4-4ac3-a958-0808a0fea46f","order_by":0,"name":"Mohammad Abu Lubad","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYDACCSB+wHAggYEh+QCID2QwGDAw8BDQkgDWkpYAYpGkJccASQsewD+7x4Ahse1OHn97ztfNvD/s8hjYm7dJMMjY4LbkzhmQlmfFEmfebrvNk5BczMBzrEyCgScNtzU3ckBaDic23MgFaWFObJDIMQNqOYxThzxMy/wbOc+AWuoTG+Tf4NdiANOy4UYOG1AL0DoJHvxaDO8cK2BIOPes2PDMM7Obc9KOJ7bxpBVbJODxi9zt5g0MH8ru5MkdT352441NdWI/++GNNz724A4xIGD/gcJlAxGJPfh0YAc/CCsZBaNgFIyCEQMA3uhbNYoE5Y8AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3658-5675","institution":"Mutah University Faculty of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Abu","lastName":"Lubad","suffix":""},{"id":228829333,"identity":"5cf14898-1fd2-436b-9c3c-7080301524fe","order_by":1,"name":"Munir Abu-Helalah","email":"","orcid":"","institution":"Mutah University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Munir","middleName":"","lastName":"Abu-Helalah","suffix":""},{"id":228829334,"identity":"102232fa-f7ce-4841-8b4e-593eafd797aa","order_by":2,"name":"Mohammad QawaQzeh","email":"","orcid":"","institution":"Mutah University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"QawaQzeh","suffix":""},{"id":228829335,"identity":"ec732d85-695a-44a6-8e1b-f53b6d60b607","order_by":3,"name":"Esra’a Alahmad Alahmad","email":"","orcid":"","institution":"Mutah University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Esra’a","middleName":"Alahmad","lastName":"Alahmad","suffix":""},{"id":228829336,"identity":"d51e9330-1ee8-46fd-854b-246d533b6002","order_by":4,"name":"Malak Al-Tamimi","email":"","orcid":"","institution":"Mutah University Faculty of 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Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rawan","middleName":"","lastName":"Alfayoumi","suffix":""},{"id":228829340,"identity":"5d4334e3-7811-4c1e-a39d-c6a7f51d81f4","order_by":8,"name":"Fatima Aldaoudeyeh Aldaoudeyeh","email":"","orcid":"","institution":"Mutah University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fatima","middleName":"Aldaoudeyeh","lastName":"Aldaoudeyeh","suffix":""},{"id":228829341,"identity":"61fa5c4e-bb9d-4590-ae03-7cfc176674db","order_by":9,"name":"Ekram AlAbabneh","email":"","orcid":"","institution":"Mutah University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ekram","middleName":"","lastName":"AlAbabneh","suffix":""},{"id":228829342,"identity":"6fc19a85-62b0-4a37-bce2-546e03a03784","order_by":10,"name":"Ahlam kharabsheh","email":"","orcid":"","institution":"Mutah University Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ahlam","middleName":"","lastName":"kharabsheh","suffix":""},{"id":228829343,"identity":"95ba4330-7b0c-498b-8324-b84eae511509","order_by":11,"name":"hussam Alshraideh","email":"","orcid":"","institution":"American University of Sharjah","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"hussam","middleName":"","lastName":"Alshraideh","suffix":""}],"badges":[],"createdAt":"2023-08-17 18:32:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3273125/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3273125/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s42506-024-00153-z","type":"published","date":"2024-04-10T15:01:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":42312827,"identity":"e1ad10ea-47cc-4df7-a5b3-b159dab283b9","added_by":"auto","created_at":"2023-08-29 14:45:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":26076,"visible":true,"origin":"","legend":"\u003cp\u003eMenstrual symptoms by reported history of COVID-19 infection. Chi-squared test p-value is 0.2969\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3273125/v1/71a4814c4b0df05cbd198d07.png"},{"id":42312826,"identity":"fed378df-428a-4fb5-91f2-3b6e266f9941","added_by":"auto","created_at":"2023-08-29 14:45:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27369,"visible":true,"origin":"","legend":"\u003cp\u003eMenstrual symptoms by type of COVID-19 vaccine. Chi-squared test p-value is 0.5016\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3273125/v1/3f0e86e3a0d3a0231ccf849f.png"},{"id":54712890,"identity":"9d34edb9-82eb-4003-8a21-23dbbf1e0785","added_by":"auto","created_at":"2024-04-15 15:13:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":519856,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3273125/v1/c639dd7b-c75e-4cbc-8cc7-666c5db68482.pdf"}],"financialInterests":"","formattedTitle":"The Effect of COVID-19 Infections and Vaccination on Menstrual Cycle Symptoms in the South of Jordan: A Cross-sectional Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMenstrual cycle (MC) is a regular sloughing of the uterine lining regulated by hormones released from hypothalamic-pituitary-gonadal axis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The length of the MC is the time between the menstrual bleeding and the onset of bleeding of the next cycle (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The normal duration of MC is between 25\u0026ndash;30 days with duration less than 21 days is known as polymenorrhagia and greater than 35 days is termed Oligomenorrhea (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The typical volume of the lost blood during the MC is about 30 ml with volumes greater than 80 ml is considered abnormal (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Globally, 5\u0026ndash;34% of MC are irregular during the childbearing age (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Different stressors implicated in the deregulating the MC including certain medications, certain viral infections, structural abnormalities, obesity, sudden weight loss, smoking, and psychological problem (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Certain viral infectons as Coronavirus (CoV) has been added as an exceptional stressor affecting MC regardless that the individuals have been infected or not (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Historically, the discovery of CoV was in 1960s. Since that, the international committees specialized in viral taxonomy have been working to classify CoV at different cluster levels (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In the past, the two most sever types of CoV associated pandemic are the severe acute respiratory syndrome coronavirus 2 (SARS) (in 2002\u0026ndash;2003) and Middle East respiratory syndrome (MERS) in 2012 (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). CoV is a zoonotic disease and transmitted through contact and droplet mechanisms (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In December 2019, the first case of Coronavirus disease 2019 (COVID-19) was identified in Wuhan, China resulting in the COVID-19 pandemic. COVID-19 is the causative agent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). COVID-19 associated disorders range from mild to fatal ones (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). By the time of writing this manuscript, COVID-19 cases in Jordan have reached 1,746,997 with 14,122 deaths while globally the number of cases have reached 676,206,330 with 6,771,699 deaths (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition to the administration vaccination as a main control of COVID-19, different treatment regimens have been prescribed to treat COVID-19 patients. One important group of drug are Statins that act by lowering the circulatory cholesterol which eventually ameliorates the vascular endothelial function (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Different vaccination predicators have been found to play an important role in the adherence of people to the vaccination programs including age, socioeconomic status, education and health literacy (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Moreover, the trust in the health environment through proper broadcasting of health information plays an important role in linking people\u0026rsquo;s information reception and vaccination intention (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). MC disorders have a substantial negative impact on quality of life and a huge socioeconomic burden for women and the health services (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Unfortunately, the COVID-19 studies particularly vaccine trials excluded its effect on the menstruation in the context of how many women have shown MC disorders, how long these persisted, and the impact of these disorders (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The COVID-19 vaccination program in Jordan started early in January 2020. The most common rerecorded side effects (SE) of these vaccines among Jordanian people including pain, swelling and redness at the site if injection, fatigue, chills, fever, myalgias, headache, and nausea (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). One the possible side effect that needs further investigations is the effect of the vaccine on the female MC. The impact of COVID-19 vaccine on the reproductive system is still not studied thoroughly. It has been shown that the COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). This receptor is highly expressed in the female reproductive system including the uterus (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The binding of the COVID-19 to the ACE2 receptor in the endometrium may be associated with the deregulation of the MC (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). After vaccination, a percentage of women experienced menstrual irregularities such as heavy menstrual bleeding (menorrhagia), frequent bleeding (metrorrhagia/ polymenorrhea), or postmenopausal bleeding (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Recently, studies emphasized the relationship between COVID-19 infection and menstrual disturbances (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). There have been limited number of published studies on the impact of COVID-19 vaccine and COVID-19 infections on the menstrual symptoms. Published studies have reported ranges of MC disturbances following COVID-19 vaccination (\u003cspan additionalcitationids=\"CR27 CR28 CR29\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The thousands of self-reported MC related issues were sent to the United States Vaccine Adverse Event Reporting System (VAERS). The United Kingdom\u0026rsquo;s Medicines and Healthcare Products Regulatory Agency (MHRA) yellow card surveillance scheme gives a strong relation between MCs changes following COVID-19 vaccination (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In Jordan, studies have shown that COVID-19 infection could affect the MC (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Moreover, it was reported that the timing of MC was alerted after vaccination among Jordanian females. It was concluded by another report from Jordan that the impact of COVID-19 vaccine on the reproductive system among Jordanian females needs further research (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). We, therefore, conducted a prospective cross-sectional study to investigate the impact of COVID-19 infections and vaccines on menstrual symptoms locally.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional survey utilizing face-to-face interviews from January first to 31 March 2022. According to national statistics, it is estimated that 51.519 females aged 15 to 50 in Karak governorate. A sample size of 382 is needed with a margin of error of 0.05 (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). The selected sample was 400 Jordanian females from the general population. We followed a multistage sampling technique from the general population through door to door approach by research coordinators. The study was conducted at the Karak governorate in the south of Jordan. We collected the study from different socioeconomics areas in Karak governorate from the city and two villages. Permission was approved before carrying on this study from the ethics committee in the faculty of medicine at Mutah University under the approval number 1002020.\u003c/p\u003e \u003cp\u003eOur research assistants started to complete the questionnaires after having a verbal consent from all volunteers. All questionnaires were completed without including the names or other identifier to maintain confidentiality.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMeasures\u003c/h2\u003e \u003cp\u003eA questionnaire consisted of fifteen questions was developed in English language by a group of experts in the field and based on the literature related to the topic of this research (\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Questionnaire was divided into three sections; the first section addressed the sociodemographic and medical history of the participants. The second section covered COVID-19 infections and vaccinations while the third section covered menstrual symptoms. Questionnaire was piloted on 30 participants and modified accordingly. Pilot data was not included in the final analysis.\u003c/p\u003e \u003cp\u003eThe participants were asked about their background characteristics, including the age, marital status, and if married they were asked about the parity and the number of abortions. The married participants asked the question regarding their contraceptive methods they are using including none, natural method (Breast feeding, coitus interruptus), oral contraception, intrauterine contraceptive device, implant, and injectable progesterone. Their age of participants' menarche was included in the questionnaire.\u003c/p\u003e \u003cp\u003eAn important question indicating their MC status including regular (21\u0026ndash;35 days, 3\u0026ndash;8 days length, average bleeding, primary dysmenorrhea), regular (21\u0026ndash;35 days, 3\u0026ndash;8 days length, average bleeding, no dysmenorrhea), irregular (\u0026lt;\u0026thinsp;21 days or 35 days), and if they are menopause. The previous medical history was also considered if they are medically free, diabetes, hypertension, thyroid disorders, polycystic ovarian syndrome, and endometriosis. Drug administration history on the use of anticoagulants (aspirin or heparin) and thyroxin was addressed in the questionnaire as these drugs known to affect the duration of menstrual following the gynecologist recommendations. Wether the participants had a history of COVID-19 infection or not was also listed in the questions. The symptoms that the participants experienced during the period after the infection and during the period after receiving the vaccine including heavy MC, intermenstrual bleeding, irregular MC, amenorrhea, dysmenorrhea, light MC, post-menopausal bleeding, and no symptoms at all. The kind of vaccine and the number of doses were also included among the questions. The date when the participants received the vaccine was mentioned and included the intervals between less one month to more than four months ago. Participants history of visiting a gynecologist for MC related complaint was included in the questioner as well.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eInclusion and exclusion criteria\u003c/h2\u003e \u003cp\u003eThe inclusion criteria were: Jordanian females reside in the selected area for at least 2 years, and having regular MCs for at least one-year prior the administration of the COVID-19 vaccination. On the other hand, the exclusion criteria included females had prior history of amenorrhea, bleeding disorders, female underwent abdominal or pelvic surgery, taking any medications that interfere with the normal MC, breastfeeding women, and diagnosis with medical condition that could influence cycle regularity, such as endometriosis, polycystic ovarian syndrome, and thyroid disorders.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eThe numbers obtained were expressed as percentages or as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. The results were interpreted after tabularizing them in frequencies and percentages. All calculations were carried out using the Statistical Package for the Social Science (SPSS); SPSS Inc., Chicago, IL, USA) version 20.0 for Microsoft Windows. The dependent variable is the symptoms during the period after the infection, while the remaining variables were considered independent (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIndependent variables were history of covid-19 infection and type of COVID-19 vaccine. Menstrual symptoms were the dependent variable. We had no issues with missing data as all interviews were done in a face to face manner.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study questionnaire was completed by 400 participants with mean age of 32.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6. The average parity was 4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 and abortion 0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6. The mean age at menarche is 13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4.\u003c/p\u003e \u003cp\u003eAs shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, half of the study participants were singles. Two third of the participants reported that they never used any sort of contraception, while 16.5% of the participants used the natural method of avoidance of fertility days. On the other hand, hormonal contraceptive methods and intrauterine contraceptive device (IUCDs) were followed by 9.8% and 9.3% of the participants respectively.\u003c/p\u003e \u003cp\u003eMenstruation status prior to COVID-19 infections and vaccines, showed a high rate of regular menstruation with primary dysmenorrhea (64%). The 14 Participants, who reported that they were on anticoagulants, were excluded from the analysis.\u003c/p\u003e \u003cp\u003eRegarding history of COVID-19 infections, 33.8% of the participants reported history of confirmed COVID-19 infections. 77.8% of them do not report any menstrual changes following the infection, while the remaining 22.2% reported changes in menstruation. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows a comparison in menstrual symptoms between participants with a history of COVID-19 and those without a history of COVID-19 infection. There was no statistically significant difference between these two groups. This figure shows that the most commonly reported post-COVID-19 symptoms were irregular MC (27.6%) and light MC (24.15) or dysmenorrhea (24.1%). Heavy menstruation was reported by 17.2% of participants post-COVID-19 infection.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBackground information of study participants (n\u0026thinsp;=\u0026thinsp;400)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAttribute\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProportion (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eMarital Status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e45.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDivorced/Widow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eContraception method used\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHormonal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIUCDs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNatural Method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e64.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eMenstruation status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIrregular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMenopause\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRegular no primary dysmenorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRegular primary dysmenorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e64.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMedical history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHistory of chronic diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedically free\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e347\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e84.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUse of Anticoagulants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e96.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHistory of Covid-19 Infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes, I got the infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo, I did not get infected by the virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e69.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003eSymptoms during the period after the infection (29 participants)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003eDependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e77.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHeavy MC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntermenstrual bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIrregular MC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDysmenorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e27.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLight MC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e24.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePost-menopausal bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e24.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003ecovid-19 vaccine type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePfizer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eIndependent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e58.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAstrazeneca\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSinopharm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e39.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSputnik\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIUCDs: intrauterine contraceptive devices\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMenstrual symptoms post COVID-19 vaccine:\u003c/h2\u003e \u003cp\u003eAll study participants reported that they have received at least one dose of COVID-19 vaccine. Majority of them (88.2%) received two doses, while 3 participants only (0.7%) received three doses. The remaining 46 participants (11.1%) received only a single dose of vaccine. Most of the study participants received either Pfizer mRNA Vaccine (58.9%) or the inactivated Sinopharm vaccine (39.1%).\u003c/p\u003e \u003cp\u003eTwo thirds of study participants (66.6%) reported no changes in the MC following COVID-19 vaccine. The most reported symptoms for those who experienced changes in the MC following the vaccination were irregular MC (13.1%), heavy menstruation (7%), light menstruation (7%). Other reported symptoms were: dysmenorrhea (4.6%), intermenstrual bleeding (1.2%), and amenorrhoea (0.5%).\u003c/p\u003e \u003cp\u003eOnly ten participants sought medical advice from a gynecologist for these symptoms. Outcomes of assessment were abnormal hormonal profile and normal ultrasound for three participants, while two participants had abnormal ultrasound and normal hormonal profile. The remaining five participants had a normal hormonal profile and normal ultrasound.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows a comparison in menstrual symptoms by type of vaccine received by study participants. There was no statistically significant difference between the three groups. The main difference between them is that participants who received other vaccines (other than Pfizer or Sinopharm) did not report irregular MC or light menstruation post-vaccination.\u003c/p\u003e \u003cp\u003eFinally, Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows a comparison between Sinopharm and Pfizer vaccines in terms of reported symptoms post-vaccination. Overall, more symptoms were reported post-Pfizer vaccine when compared with the Sinopharm vaccine. Amenorrhea and intermenstrual bleeding were reported by two and five participants who received the Pfizer vaccine. On the other hand, these two symptoms were not reported by participants who received the Sinopharm vaccine.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison in the proportion of self-reported menstrual changes between Sinopharm and Pfizer COVID-19 vaccines\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSinopharm\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePfizer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProportion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProportion\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIrregular MC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLight MC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.5589\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeavy MC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.8274\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysmenorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.6326\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntermenstrual bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.1752\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmenorrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.6753\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-menopausal bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eSeveral recent studies and reports have highlighted the need for more evaluation of the impact of COVID-19 infections and vaccines on the reproductive system and menstruation. Published data so far are not robust enough to draw a firm conclusion. We conducted a local study in Jordan on women within reproductive age group from general population. Our findings revealed an overall mild change in the menstrual symptoms due to COVID-19 infections or vaccines. All participants received COVID-19 vaccines; most received at least two doses. Pfizer and Sinopharm vaccines were the most widely received vaccines. Post-vaccination menstrual changes were also mild with no statistically significant differences between vaccines.\u003c/p\u003e \u003cp\u003eThree quarters of our sample did not report any menstrual changes following COVID-19 infection. The most common reported menstrual symptoms for women, who experienced changes in the MC, were irregular MC, light MC, and dysmenorrhea. Heavy menstruation was reported by small proportion of the study participants. Our results are consistent with the finding of a recent systematic review. This systematic search was conducted on the Medline, Scopus, and Cochrane Library databases to assess the impact of COVID-19 infection on MC. Only three studies were included in the final analysis. Results of this review revealed that SARS-CoV-2 led to menstrual irregularity with decreased menstrual volume and prolonged cycle as the commonest two reported symptoms (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnother study from Ireland included 1031 women of reproductive age who completed an anonymous digital survey as part of an observational study of women\u0026rsquo;s reproductive health over the course of the pandemic (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Around half of the participants (46%) reported a change in their MCs since the beginning of the pandemic. This study revealed significant changes in the MC when compared with the pre-pandemic period. Participants reported significantly more menorrhagia, dysmenorrhea, and a worsening of premenstrual symptoms than before the pandemic. However, this study did not report the proportion of participant who had confirmed COVID-19 infections, and, therefore, the stress level, as described below, could play a major role in the reported symptoms. Another study from China showed consistent results with our findings (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This study evaluated the effects of COVID-19 infection on the sex hormones and menstrual changes among women with confirmed COVID-19 infection. This study revealed that approximately 20% of the patients had a significant decrease in menstrual volume, without a significant difference by disease severity. Approximately 20% of COVID-19 patients showed prolonged MCs. A smaller proportion of participants reported an increase in menstrual volume and/or MC shortening. Similar finding were reported from Arizona, USA with 16% (n\u0026thinsp;=\u0026thinsp;20) of the participants reported MC changes following COVID-19 infection (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eChanges in the menstrual symptoms could be related to the viral infection with SARS-CoV-2 or due to the changes in the stress level associated with the infection state (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Infection with SARS-CoV2 affects the immune system and causes an increase in interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) and other cytokines. This is in addition to the potential alteration on hypothalamic\u0026ndash; pituitary\u0026ndash;gonadal axis due to this infection (\u003cspan additionalcitationids=\"CR42 CR43\" citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHigh stress levels due to the infection or the pandemic worldwide are associated with menstrual irregularities COVID-19 pandemic has changed life worldwide. It has been associated with different stressors such as losing loved ones, losing jobs, and health changes due to the infection (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). A recent study has revealed a significant prolongation of menses and heavier menstruation among participants with a high perceived stress scale (PSS) compared to those with a moderate COVID-19 PSS (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSimilar to our findings, a range of MC changes after COVID-19 vaccination have been reported in several studies, including longer and shorter cycles, missed cycles, heavier and lighter menstrual flow, and intermenstrual spotting (\u003cspan additionalcitationids=\"CR48\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e). The main limitation of the scientific evidence related to COVID-19 vaccines impact on reproductive health is that clinical trials of covid-19 vaccines did not include menstrual changes within their outcomes. The impact of COVID-19 vaccines on MC were assessed in our study based on participants\u0026rsquo; own reporting. Two thirds of study participants reported no changes in the MC following COVID-19 vaccine. The most reported symptoms for those who experienced changes in the MC following the vaccination were irregular MC, heavy menstruation, and light menstruation. Our results are consistent with international reports and published studies. A US only cohort provides further evidence of small cycle length changes associated with covid-19 vaccination and support our findings (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e). A recently published study from Italy revealed that 50 to 60% of reproductive-age women experienced MC irregularities, regardless of the type of the received COVID-19 vaccine. The incidence of the symptoms was a slightly higher (60\u0026ndash;70%) following the second dose of the vaccine. The most common reported changes were shorter MCs, longer cycles, and heavier menstruation than was expected and usual (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). Difference in results between our study from Jordan and this Italian study is that around 40% of our sample received the inactivated Sinopharm vaccine. While the Italian study population mainly received mRNA vaccines. This could justify difference in the proportion of reported symptoms.\u003c/p\u003e \u003cp\u003eAn important cohort study from the USA showed the resolution of menstrual changes in the cycle post vaccine. This study also revealed that the cycle length changes associated with mRNA vaccines do not appear to differ from those with other vaccine mechanisms. These finding reassure women about the reversibility of menstrual changes post COVID-19 vaccines (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe strength points of this study are the prospective data collection regarding the MC which limits the bias associated with memorizing MC features among participants and the face to face method of data collection which was helpful to identify the small clinical difference in the MC that might be missed by the participants. The main limitation of our study lies in the differences in intervals post-vaccination between study participants. Additionally, it is based on self-reported changes post-COVID vaccines through retrospective approach subjecting the findings to recall bias. However, our analysis results are consistent with published studies on the impact of COVID-19 infection and vaccines.\u003c/p\u003e \u003cp\u003eThis is the first published study from Jordan on the impact of COVID-19 infection and vaccine on menstrual symptoms. It revealed minor changes in the MC. It is recommended that future clinical trials for new vaccines for women within childbearing age to include outcomes related to sex hormones and MC. Women should be encouraged to take the vaccines and to report symptoms to healthcare professionals for further assessment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval to conduct the present study was obtained from the ethics committee of the Faculty of Medicine, University of Mutah under the permission number 1002020. All procedures were performed in accordance with the ethical standards of the institutional and/or national research committees and the Declaration of Helsinki and its later amendments, or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll datasets generated or analyzed during this study are included in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declared that they have no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was not financially supported by any organization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank everyone who participated in the survey particularly the staff of Gynecology department in Al-Karak Governmental Hospital.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWang C, Pan R, Wan X, Tan Y, Xu L, Ho CS, et al. 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Inte J Women\u0026rsquo;s Health Reprod Sci. 2021;9(3):158-9.\u003c/li\u003e\n\u003cli\u003eLi K, Chen G, Hou H, Liao Q, Chen J, Bai H, et al. Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age. Reproductive biomedicine online. 2021;42(1):260-7.\u003c/li\u003e\n\u003cli\u003eEdelman A, Boniface ER, Male V, Cameron ST, Benhar E, Han L, et al. Association between menstrual cycle length and covid-19 vaccination: global, retrospective cohort study of prospectively collected data. BMJ Medicine. 2022;1(1).\u003c/li\u003e\n\u003cli\u003eAlvergne A, Von Woon E, Male V. Effect of COVID-19 vaccination on the timing and flow of menstrual periods in two cohorts. Frontiers in Reproductive Health. 2022;4:952976.\u003c/li\u003e\n\u003cli\u003eWang S, Mortazavi J, Hart JE, Hankins JA, Katuska LM, Farland LV, et al. A prospective study of the association between SARS-CoV-2 infection and COVID-19 vaccination with changes in usual menstrual cycle characteristics. 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Journal of clinical and diagnostic research: JCDR. 2015;9(3):QC01.\u003c/li\u003e\n\u003cli\u003eOzimek N, Velez K, Anvari H, Butler L, Goldman KN, Woitowich NC. Impact of stress on menstrual cyclicity during the coronavirus disease 2019 pandemic: a survey study. Journal of Women\u0026apos;s Health. 2022;31(1):84-90.\u003c/li\u003e\n\u003cli\u003eAlvergne A, Kountourides G, Argentieri A, Agyen L, Rogers N, Knight D, et al. COVID-19 vaccination and menstrual cycle changes: A United Kingdom (UK) retrospective case-control study. MedRXiv. 2021.\u003c/li\u003e\n\u003cli\u003eMale V. Menstrual changes after covid-19 vaccination. British Medical Journal Publishing Group; 2021.\u003c/li\u003e\n\u003cli\u003eTrogstad L. Increased occurrence of menstrual disturbances in 18-to 30-year-old women after COVID-19 vaccination. Available at SSRN 3998180. 2022.\u003c/li\u003e\n\u003cli\u003eCohort A. Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination. Obstet Gynecol. 2022;139:1-9.\u003c/li\u003e\n\u003cli\u003eLagan\u0026agrave; AS, Veronesi G, Ghezzi F, Ferrario MM, Cromi A, Bizzarri M, et al. Evaluation of menstrual irregularities after COVID-19 vaccination: Results of the MECOVAC survey. Open Medicine. 2022;17(1):475-84.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-the-egyptian-public-health-association","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jepa","sideBox":"Learn more about [Journal of the Egyptian Public Health Association](http://jepha.springeropen.com)","snPcode":"42506","submissionUrl":"https://submission.nature.com/new-submission/42506/3","title":"Journal of the Egyptian Public Health Association","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Jordan, COVID-19, Menstrual cycle, COVID-19 vaccine","lastPublishedDoi":"10.21203/rs.3.rs-3273125/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3273125/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeveral recent studies and reports have highlighted the need for more evaluation of the impact of COVID-19 infections and vaccines on the reproductive system and menstruation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eA cross-sectional survey utilizing face-to-face interviews from 1 October to 31 December 2021 was conducted in the city of Kerak in the southern part of Jordan. The study questionnaire assessed the impact of COVID-19 infection and vaccines on menstrual symptoms. It included sociodemographic characteristics, medical and reproductive history, the contraceptive method, MC status, previous medical and drug history, and the effect of infection and vaccination on the MC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study questionnaire was completed by 400 participants with a mean age of 32.1±12.6. Regarding the history of COVID-19 infections, 33.8% of the participants reported a history of confirmed COVID-19 infections. 77.8% of them do not report any menstrual changes following the infection, while the remaining 22.2% reported changes in menstruation. The most commonly reported post-COVID-19 symptoms were irregular MC (27.6%) and light MC (24.15) or dysmenorrhea (24.1%). Heavy menstruation was reported by 17.2% of participants post-COVID-19 infection.\u003c/p\u003e\n\u003cp\u003eTwo-thirds of study participants (66.6%) reported no changes in the MC following the COVID-19 vaccine. The most reported symptoms for those who experienced changes in the MC following the vaccination were irregular MC (13.1%), heavy menstruation (7%), and light menstruation (7%). Other reported symptoms were: dysmenorrhea (4.6%), intermenstrual bleeding (1.2%), and amenorrhoea (0.5%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is the first published study from Jordan on the impact of COVID-19 infection and vaccine on menstrual symptoms. It revealed minor changes in the MC following COVID-19 infections and the COVID-19 vaccine. These findings are consistent with published reports. It is recommended that future clinical trials for new vaccines for women within childbearing age to include outcomes related to sex hormones and MC. Women should be encouraged to take the vaccines and to report symptoms for healthcare professionals for further assessment.\u003c/p\u003e","manuscriptTitle":"The Effect of COVID-19 Infections and Vaccination on Menstrual Cycle Symptoms in the South of Jordan: A Cross-sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-29 14:45:21","doi":"10.21203/rs.3.rs-3273125/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-10-21T07:10:18+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2023-09-27T09:27:04+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-08-25T09:06:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-21T00:25:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of the Egyptian Public Health Association","date":"2023-08-17T14:32:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-the-egyptian-public-health-association","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jepa","sideBox":"Learn more about [Journal of the Egyptian Public Health Association](http://jepha.springeropen.com)","snPcode":"42506","submissionUrl":"https://submission.nature.com/new-submission/42506/3","title":"Journal of the Egyptian Public Health Association","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"68eec518-2ac9-43fb-81bd-d577d695653c","owner":[],"postedDate":"August 29th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-04-15T15:08:29+00:00","versionOfRecord":{"articleIdentity":"rs-3273125","link":"https://doi.org/10.1186/s42506-024-00153-z","journal":{"identity":"journal-of-the-egyptian-public-health-association","isVorOnly":false,"title":"Journal of the Egyptian Public Health Association"},"publishedOn":"2024-04-10 15:01:38","publishedOnDateReadable":"April 10th, 2024"},"versionCreatedAt":"2023-08-29 14:45:21","video":"","vorDoi":"10.1186/s42506-024-00153-z","vorDoiUrl":"https://doi.org/10.1186/s42506-024-00153-z","workflowStages":[]},"version":"v1","identity":"rs-3273125","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3273125","identity":"rs-3273125","version":["v1"]},"buildId":"KtUs4DrQ-CGpW-FBV7kM3","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}