Impact of COVID-19 vaccination on menstruation pattern among female nursing and paramedical students in a peripheral medical college in Eastern India

Ayan Goswami; Arup Kumar Majhi; Arunima Chaudhuri; Pratip Kundu

doi:10.4103/cmi.cmi_105_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 21 | Issue : 2 | Page : 104-109

Impact of COVID-19 vaccination on menstruation pattern among female nursing and paramedical students in a peripheral medical college in Eastern India

Ayan Goswami¹, Arup Kumar Majhi², Arunima Chaudhuri³, Pratip Kundu⁴
¹ Department of Physiology, Santiniketan Medical College, Bolpur, Birbhum, West Bengal, India
² Department of G and O, Santiniketan Medical College, Bolpur, Birbhum, West Bengal, India
³ Department of Physiology, Burdwan Medical College, Burdwan, West Bengal, India
⁴ Department of Microbiology, Santiniketan Medical College, Bolpur, Birbhum, West Bengal, India

Date of Submission	24-Sep-2022
Date of Decision	17-Nov-2022
Date of Acceptance	29-Nov-2022
Date of Web Publication	07-Apr-2023

Correspondence Address:
Dr. Arunima Chaudhuri
Krishnasayar South, Borehat, Burdwan - 713 102, West Bengal
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/cmi.cmi_105_22

Abstract

Background: Many females worldwide have reported abnormalities in their menstrual patterns post-COVID-19 vaccination. The present study was conducted to determine the impact of the COVID-19 vaccination on menstrual patterns among female nursing and paramedical students at a peripheral medical college in eastern India. Materials and Methods: The cross-sectional, online self-administered survey was conducted using Microsoft Forms after taking institutional ethical clearance and informed consent from the participants. Two hundred BSc nursing and paramedical students who had received two doses of COVID vaccination (Covaxin or Covishield) and were not suffering from any endocrinopathies, bleeding disorders, structural gynecological abnormalities, or taking any medication known to affect the hypothalamic–pituitary–gonadal axis were included in the study. The questionnaire included menstrual length cycle length and amount of bleeding and there were no direct identifiers. Results: The participants reported a significant increase in the amount of bleeding on the heaviest day (mean ± standard deviation [SD] of the number of pads used was 3.52 ± 1.15 during prevaccination months vs. 4.64 ± 1.36 during postvaccination months; P < 0.001) following vaccination. A similar result of increased bleeding on the heaviest day of the period was obtained in both the Covaxin group (mean ± SD: 3.08 ± 1.16 vs. 4.88 ± 1.53; P: 0.001) and the Covishield group (mean ± SD: 3.59 ± 1.13 vs. 4.6 ± 1.34; P < 0.001). No difference in change in the menstrual pattern was observed between the two groups who had received two different types of vaccine (P: 0.527). Conclusion: The study showed a possible connection between the COVID-19 vaccination and the change in menstrual patterns.

Keywords: COVID-19 vaccination, menstrual pattern, perceived stress, waist/hip ratio

How to cite this article:
Goswami A, Majhi AK, Chaudhuri A, Kundu P. Impact of COVID-19 vaccination on menstruation pattern among female nursing and paramedical students in a peripheral medical college in Eastern India. Curr Med Issues 2023;21:104-9

How to cite this URL:
Goswami A, Majhi AK, Chaudhuri A, Kundu P. Impact of COVID-19 vaccination on menstruation pattern among female nursing and paramedical students in a peripheral medical college in Eastern India. Curr Med Issues [serial online] 2023 [cited 2023 Jun 4];21:104-9. Available from: https://www.cmijournal.org/text.asp?2023/21/2/104/373752

Introduction

It is now a known fact that COVID-19 vaccination can protect against fatal outcomes in hospitals. Like all the countries worldwide, India had also begun its COVID-19 vaccination drive initially with two available vaccines: Covaxin and Covishield. As the vaccination drive progressed in India, people were much worried and concerned about the side effects that the vaccine can impart them. Not only people with existing comorbidities but even normal healthy individuals also approached their physicians and inquired about the possible side effect of the vaccination. During the lockdown period, communication through social media influenced a lot of people's minds. Cross-country communication had also increased manyfold. With few reports coming on the news and social media about changes in menstrual patterns following vaccination Indian women had also developed concern and that caused hesitation among Indian women in taking the doses. The United Kingdom Medicine and Healthcare Products Regulatory Agency had reported cases of unexpected vaginal bleeding following vaccination.^[1] In the United States, the appropriate authority also recorded cases of changes in menstrual patterns.^[2],[3]

The regular and cyclical menstrual pattern is a component of good reproductive health among women of the reproductive age group. Mental stress is known to affect the HPA axis and subsequently periodic menstruation cycle. Many known stressors can affect and stimulate the HPA axis and thereby change the cyclical pattern of secretion of ovarian hormones primarily responsible for healthy menstruation. This stimulation can also be viewed as a catabolic response of the body that redistributes fuels for metabolism to meet energy requirements.^[4] Abnormal body fat distribution again can be the result of chronic stress. Chronic stress results in increased activity along the hypothalamic–adrenal axis and plays a role in the preferential deposition of fat in the abdomen.^[5] As a result, menstrual abnormalities can be seen in women with abnormal body fat distribution.

There is a concern among vaccine-recipient Indian females as well in the reproductive age group that COVID-19 vaccination may lead to menstrual irregularity. Considering the vaccine as a stressor to influence the HPA axis, at least theoretically there is a possibility that COVID vaccination might disturb or change the menstrual pattern. Many social media sites also mention that menstrual disturbance happened after the COVID vaccination but that was temporary.^[6],[7]

A study on the Indian population can help us address the issue and resolve the concern of young menstruating women about any possibility of menstrual patterns getting affected after COVID-19 vaccination. We performed a cross-sectional observational study to determine whether COVID-19 vaccination in India (Covaxin manufactured by Bharat Biotech, developed by ICMR, and Covishield manufactured by Serum Institute of India, developed by Oxford University) is associated with any change in menstrual patterns in Indian women of the reproductive age group in terms of total cycle length, periods duration, and amount of bleeding on the heaviest day of the period. We have also compared those parameters between Covaxin receiver women and Covishield receiver women. Covaxin is killed whole virus particle vaccine, whereas Covishield is the capsular spike protein of the COVID-19 virus incorporated in the chimpanzee adenovirus.

Methodology and Participants

Study settings, design, period, and ethical considerations

This cross-sectional observational study was conducted after taking institutional ethical clearance (SMC/IEC/0001 dated 02/06/2022) and the informed consent of the participants in 6 months. The sample size calculation was calculated using an online sample size calculator available at calculator.net. There are 414 BSc nursing students and paramedical female students studying in the institution. The calculated sample size came to 198 (confidence interval 95%, the margin of error 5%, and population proportion was considered 50%).

Inclusion criteria

Female students aged between 18 and 25 years who have taken two doses of COVID-19 vaccination and studying in the nursing or paramedical college of the institution.

Exclusion criteria

Individuals on oral contraceptive pills, thyroid disorders, dysfunctional uterine bleeding (DUB), known structural uterine diseases such as polyps, adenomyosis, leiomyoma, malignancy, congenital anomalies (unicornuate or bicornuate uterus), polycystic ovary syndrome (PCOS), known coagulation disorder, postpregnancy, and individuals with high perceived stress score (COHEN's PSS more than 26).

Study tools

The Perceived Stress Scale (PSS-10) is a 10-item questionnaire created by Cohen et al. It is widely used to determine stress level in young individuals aged >12 years and in adults. It evaluates the degree to which an individual has perceived life as unpredictable, uncontrollable, and overloading over the past month. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress. Scores ranging from 0 to 13 would be considered low stress. Scores ranging from 14 to 26 would be considered moderate stress. Scores ranging from 27 to 40 would be considered high perceived stress.^[8]

Sampling technique

Four hundred and fourteen BSc nursing and paramedical female students aged between 18 and 25 years who gave consent for the study were initially recruited. After getting all data from all 414 female students, it was seen that out of them 275 students had taken complete two doses of COVID vaccination. Those who were taking oral contraceptive pills (OCPS), having thyroid disease, DUB, and known structural uterine diseases such as polyps, adenomyosis, leiomyoma, malignancy, congenital anomalies (unicornuate or bicornuate uterus), PCOS, known coagulation disorder, and postpregnancy and individuals with high perceived stress score (COHEN's PSS more than 26) were excluded from the study. Finally, 200 participants were recruited for the study.

Methods

All students were given copies of consent forms in Bengali, English, and Hindi languages as per their convenience and were signed by them. First, they were asked to fill out an online Microsoft Forms which included the participants to state their age, anthropometric measurements (for waist/hip ratio: [WHR]), previous medical or surgical (if any) history, COVID vaccination history (related to inclusion and exclusion criteria of the current study) and menstrual history and their perceived stress scale (PSS). Participants were trained beforehand on how to calculate Cohen's Perceived Stress Score using two sensitization workshops. Questions on the menstrual pattern were as follows:

Before vaccination (consecutive 3 months history immediately before vaccination)

Periods used to come every ________ day (average)
Average duration of period_ ________ days.
Number of pads/tampons used on heaviest day ________

After completion of the final dose or second dose of vaccine (consecutive 3 months history immediately after vaccination)

Periods used to come every _ ________ day (average)
Average duration of period_ ________ days.
Number of pads/tampons used on heaviest day ________

Above-mentioned Microsoft Forms was anonymous and we did not record personal details such as the name, phone numbers, or E-mail IDs of the individuals. All data were kept confidential and not shared with anybody other than the investigators. The concerned Microsoft account was strongly password protected and two-step verification was made.

Participants were divided into two groups: the Covaxin group and the Covishield group depending on the vaccine they had taken. Both groups were matched initially by age, PSS, and WHR [Table 1] as these two parameters are known to influence the HPA axis and thereby may affect menstrual patterns.^[9],[10] Prevaccination menstrual parameters (cycle length, period duration, and the number of pads used on the heaviest day of the period) were also initially matched.

Table 1: Comparison of age, waist/hip ratio, and Perceived Stress Scale of the Covaxin group and Covishield group

Click here to view

Statistical analysis

Data analysis was done using Jamovi software. Statistical tests used were the Chi-square test for comparing categorical data between groups and paired and unpaired t-test for comparing numerical or continuous variable data between groups. P < 0.05 was considered statistically significant and a P < 0.01 was considered highly significant.

Results

Both Covaxin and Covishield groups were matched concerning their age, WHR, Perceived Stress Score (PSS), and menstruation parameters (cycle length, period duration, and amount of bleeding on the heaviest day of the period) at the beginning of the study [Table 1].

All participating individuals were compared before and after vaccination in terms of their cycle length, period duration, and the number of pads/tampons used on the heaviest day of the period. Each group was separately studied and those parameters were compared before and after vaccination. Comparisons between the two groups were also done after vaccination.

No significant difference in cycle length before and after vaccination was observed using the Chi-square test with a Chi-square value of 0.082 and a P = 0.96. For the Covaxin group (n = 41), only cycle length did not change the following vaccination with a Chi-square value of 0.38 and P = 0.82. A similar result was obtained for the Covishield group (n = 159) with a Chi-square value of 0.26 and P = 0.87 [Table 2].

Table 2: Comparison of the cycle length of all participants between pre- and postvaccination months

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The duration of the menstrual cycle did not change significantly from 4.75 ± 1.06 days during prevaccination months to 4.94 ± 1.18 days during postvaccination months with a P = 0.15. For Covaxin and Covishield groups, prevaccination period durations were 4.56 ± 0.8 days and 4.8 ± 1.11 days, respectively, and during the postvaccination months, period durations were 4.75 ± 0.84 days and 4.99 ± 1.25 days, respectively. For both Covishield and Covaxin groups, changes in the menstrual cycle duration were not significant with a P = 0.36 for the Covaxin group and 0.23 for the Covishield group [Table 3].

Table 3: Comparison of cycle length in each group before and after vaccination

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Overall, the number of pads used on the heaviest day (or bleeding amount on the heaviest day) increased significantly from 3.52 ± 1.15 during prevaccination months to 4.64 ± 1.36 during postvaccination months with a P < 0.001. For the Covaxin group, the number was 3.08 ± 1.16 versus 4.88 ± 1.53 during prevaccination and postvaccination months, respectively with a P = 0.0013. The Covishield group also increased significantly from 3.59 ± 1.13 during prevaccination months to 4.6 ± 1.34 during postvaccination months with a P < 0.001 [Table 4].

Table 4: Comparison of period duration and bleeding amount on the heaviest day before and after vaccination

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Both Covaxin and Covishield groups were matched at the beginning of the study concerning their menstrual pattern parameters. After complete vaccination, there was no significant difference in cycle length between the two groups with a Chi-square value of 4.18 and a P = 0.12. After the vaccination period, durations were 4.75 ± 0.84 days and 4.99 ± 1.25 days for Covaxin and Covishield groups, respectively, with a P = 0.2. The difference in bleeding amount on the heaviest day of the period was also not significant between the two groups during postvaccination months (4.88 ± 1.53 pads for the Covaxin groups vs. 4.6 ± 1.34 pads for the Covishield group with a P = 0.52) [Table 5] and [Table 6].

Table 5: Comparison between the Covaxin group and Covishield group in cycle length before and after vaccination

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Table 6: Comparison between the Covaxin group and Covishield group in periods duration and bleeding amount on the heaviest day before and after vaccination

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Discussion

In the present study, we have seen that females in the age group of 18–25 years had menstrual changes after taking doses of COVID-19 vaccination. This abnormality does not affect the menstrual cycle length or period duration but caused increased bleeding on the heaviest day of the period. Vaccine type (Covaxin or Covishield) did not affect the pattern. Cyclical periodic bleeding ensures the proper release of gonadotropins and ovarian hormones.^[11] Many menstruation-related symptoms such as dysmenorrhea, perimenstrual pain syndrome, and cramps are considered common issues.^[12] A study that was conducted by Schoep ME et al. on apparently healthy Dutch women in the reproductive age group, reported that 53.7% had complaints of heavy bleeding, 77.3% had psychological problems during menstruation, and 85.4% had menstrual cramps.^[12] All these symptoms can be due to several factors that can either on a short-term basis or long-term basis can change menstrual patterns. Such factors might be infections, weight gain, anxiety, hormonal changes, periods of psychological stress or endocrinopathies, and polycystic ovarian disease.^{[13],[14],[15]} Stressors have been known to activate the hypothalamic–pituitary–gonadal axis, leading to a disruption of the regularity of hormone release. Such changes can hinder women's quality of life, leading to work limitations. Hence, we excluded females with higher stress levels in the present study and both groups in the study were PSS matched.

Specific vaccine components or immune-mediated responses might be responsible for menstrual pattern changes following COVID-19 vaccination. Menstrual changes have been reported by women receiving mRNA vaccine as well as adenovirus vector vaccines worldwide.^[1] It is more likely that the immune response following vaccination had a greater influence on the menstrual pattern. Studies have shown that vaccination against human papillomavirus caused menstrual changes in women.^[16] The menstrual pattern can be changed by immune activation in response to various stimuli, including viral infection. A study of menstruating women also showed around 25% of SARS-CoV-2-infected women had experienced at least some degree of menstrual disruption.^[17]

Menstrual changes might be secondary to immunological influence on the release of gonadotropin and ovarian hormones that drive the regular periodic menstrual cycle, i.e., the building and shedding of lining tissues of the uterus. Immune cells located in uterine tissue might also have a role in mediating the changes in menstruation.^[18]

How menstrual patterns can be significantly affected by COVID vaccination is not known clearly. Few previous studies had mentioned immune-mediated thrombocytopenia as a cause of menstrual pattern changes after some other vaccinations including measles–mumps–rubella, hepatitis A and B, diphtheria–tetanus–acellular pertussis, varicella, and even influenza.^[19],[20]

If we consider COVID-19 infection, there are multiple ways the infection can lead to changes in menstrual patterns. First, COVID-19 infection can cause anxiety and depression which secondarily affect the premenstrual luteinizing hormone (LH) surge and causes a change in menstrual pattern. Second, the SARS-CoV-2 virus is known to attack cells through angiotensin-converting enzyme type 2 (ACE-2) on the cell surface. Not only pneumocytes and vascular endothelium but ACE-2 receptors are also present on the surface of many other cell types. Developing ovarian follicle and uterine mucosal lining cells also contain such receptors. The binding of virus particles to those receptors may cause functional abnormalities in those cells leading to changes in menstrual patterns. Third, COVID-19 infection causes the release of many cytokines such as interleukin-6, interleukin-8, and tumor necrosis factor-alpha which mediates inflammation. All these cytokines can impose a procoagulant local environment which may disrupt the menstrual pattern.^{[21],[22],[23],[24]}

Our study observed a change in the menstrual pattern after two doses of COVID-19 vaccination. How far the above-mentioned mechanisms for change in a menstrual pattern following infection can apply to the change in a menstrual pattern following vaccination is not yet clear.

Limitations

The study was based on the history given by the study participants regarding their menstrual patterns before and after completing two doses of vaccination. The cross-sectional design of the study cannot determine any causal relationship between vaccination and menstrual irregularities. Moreover, self-reported data have an increased chance of recall bias. Participants had to recall their patterns before vaccination. Had it been a prospective study, such issues could have been avoided. Second, participants may have unknown endocrine disorders which could not be ruled out in this study. Third, WHR was taken as an indicator of body fat distribution. Abdominal-to-peripheral body fat ratio using Dual Energy X-ray Absorptiometry (DXA) would have been a more accurate indicator for body fat distribution.

Conclusion

The study showed a possible connection between the COVID-19 vaccination and menstrual pattern change. Our study did not demonstrate any change in menstrual cycle length and period duration, but the bleeding was significantly raised on the heaviest day.

Acknowledgments

The authors would like to thank all participants of the study.

Research quality and ethics statement

All authors of this manuscript declare that this scientific study complies with standard reporting guidelines set forth by the EQUATOR Network. The authors ratify that this study required Institutional Review Board/Ethics Committee review; hence, prior approval was obtained, SMC/IEC/0001 dated 02/06/2022. We also declare that we did not plagiarize the contents of this manuscript and have performed a plagiarism check.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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