Abstract
Background:
COVID-19 vaccines have provided fertile ground for research, especially with the unprecedented spread of misinformation about this disease and its vaccines. Among women, one of the most frequently reported side effects of the vaccine has been menstrual disturbance.
Objective:
To investigate the perceived impact of COVID-19 vaccines on the menstrual cycle. In addition, the research seeks to identify factors that could predispose certain individuals to experience these effects, thereby contributing to a deeper understanding of the interplay between vaccines and menstrual health.
Design:
We conducted a retrospective observational cross-sectional study.
Methods:
Any woman of menstruating age who received at least one dose of the COVID-19 vaccine and currently resides in Saudi Arabia was invited to complete an online questionnaire. The questionnaire compared menstruation characteristics—regularity, volume, intermenstrual bleeding, and dysmenorrhea—before and after receiving the COVID-19 vaccine, taking into consideration possible predisposing factors such as polycystic ovarian syndrome, contraceptives, or period-blocking pills.
Results:
Women without polycystic ovarian syndrome experienced less change in dysmenorrhea post-vaccine compared to those with polycystic ovarian syndrome (23.88% versus 37.78%, p = 0.045). Women using hormonal contraceptives were about two times more likely to experience changes in volume compared to those not using contraceptives (odds ratio = 2.09, 95% confidence interval = 1.23–3.57, p = 0.006). COVID-19 vaccine skeptics were about three times more likely to perceive changes in regularity post-vaccine compared to non-skeptics (odds ratio = 2.96, 95% confidence interval = 1.79–4.90, p < 0.001). They were also three times more likely to perceive changes in volume post-vaccine (odds ratio = 3.04, 95% confidence interval = 1.95–4.74, p < 0.001).
Conclusion:
Our data suggest significant associations between COVID-19 skepticism, the use of hormonal contraceptives, and the reported post-vaccine menstrual disturbances. This underscores the importance of public education efforts aimed at dispelling misinformation and addressing controversies related to these vaccines.
Introduction
As the COVID-19 pandemic slows down to an expected end, new challenges begin. In an age where information—or misinformation—is readily available and can be easily spread, truths and myths run rampant, driven by the fear of a recently threatened public. The COVID-19 vaccines, in particular, have been the focus of unprecedented controversy, which has split the public into those who are hopeful about the vaccines and those who are fearful. For the former, the vaccines reaffirmed their belief in the global healthcare system, while for the latter they sparked a disdainful mistrust toward scientists fueled by conspiracy theories.1,2
The Saudi Ministry of Health announced the availability of COVID-19 vaccines for adults starting 6 January 2021; and on 27 June of the same year, it became available for minors ages 12–18 years. 3 According to the World Health Organization’s COVID-19 dashboard, as of 11 March 2023, 77.61% of the Saudi population received at least one dose of COVID-19. 4 Since the start of the mass vaccination against COVID-19, one of the most subjectively reported side effects, locally and globally, has been dysregulated menstrual cycles.1,5 –9 This should come as no surprise, given that the process of menstruation is tightly controlled by the endocrine system through the hypothalamus, pituitary gland, ovaries, and uterus endometrium. The rigidity of this regulation makes menstruation highly sensitive to internal as well as external stressors, either physical, psychological, or social. Normally, an impact of this type results in short-lived changes in the regularity or characteristics of menstruation. 5
The association between these changes and COVID-19 vaccines is the subject of ongoing research across the globe.6 –8 In Saudi Arabia, Alghamdi et al. 6 surveyed overall COVID-19 vaccine side-effects in 4170 individuals. They reported palpitation as the number one adverse event, followed by abnormal menstrual cycles (abnormalities including delay, menorrhagia, or dysmenorrhea), and deep vein thrombosis in a single case. In the United States, Edelman et al. 7 conducted a prospective cohort study involving 2403 women who were monitored for three menstrual cycles before and after receiving COVID-19 vaccines. In addition, they followed 1556 unvaccinated women for the same duration. Their study revealed that vaccinated women experienced a minimal change of less than one day in their cycle length, while the cycle length of unvaccinated women remained unchanged. Moreover, the researchers concluded that the vaccine did not have a significant effect on menses length overall. Mahasing et al. 9 suggested that anxiety-related reactions could be a primary factor behind adverse effects seen in some women after receiving COVID-19 vaccinations in Thailand. Similarly, a multinational study conducted in Arab countries revealed a significant level of vaccine hesitancy among the Arab population (51%), 10 which may also contribute to the development of post-vaccine side-effects.
However, the evidence concerning factors potentially linked to changes in post-vaccine menstruation remains limited. 11 Notably, there is a significant research gap surrounding the association between vaccine skepticism and post-vaccine menstruation, particularly in the context of COVID-19 vaccines. To address this gap, our article investigated the effects of COVID-19 vaccines on the menstrual cycle. Specifically, our goal was to identify factors that could lead to the worsening or new onset of dysmenorrhea, intermenstrual bleeding, or heavier flow volume after vaccination. The results of this study have the potential to assist healthcare professionals, policymakers, and public health authorities in creating targeted educational campaigns to address vaccine skepticism and misconceptions more effectively.
Materials and methods
This is a retrospective, observational, cross-sectional study conducted to assess and identify the factors associated with menstrual cycle changes following vaccination against COVID-19. All participants were assigned female at birth, residing in Saudi Arabia, and within the age range of 18 to 55 years, all of whom were experiencing menstruation. To be eligible, participants needed to have received at least one dose of any COVID-19 vaccine. Post-menopausal women, pre-menarche girls, minors, and unvaccinated women were excluded. As a convenience sampling method was used, no sample size calculation was determined. 12 STROBE Guidelines were followed in the preparation of the article.
Data collection
The data were gathered through the administration of an online questionnaire (see Supplemental material) using the Google Forms platform. Participants were invited to take part in the study through a link that provided them with a detailed overview of the study's objectives and procedures. In addition, the link included a consent form that participants were required to read and acknowledge prior to engaging in the questionnaire.
The questionnaire consisted of 32 questions divided into seven sections on demographics (age, nationality, city of residence, and occupation), COVID-19 history (including vaccination), chronic illnesses, pre-vaccine menstrual history, sexual history (including the use and type of contraception and period-blocking pills), post-vaccine menstrual history, and vaccine skepticism (yes or no). Participants were asked to reflect on their menstrual characteristics before receiving any vaccine dose. For example, on regularity, the question was: how regular was your cycle before receiving COVID-19 vaccine? And the options provided were: regular, somewhat regular, irregular, or I don’t remember. The last option was an attempt at minimizing recall bias. The same question was raised again in the post-vaccine section of the questionnaire without the last option. The rest of the questions followed a similar pattern. In addition, the chronic illnesses section was provided particularly for polycystic ovarian syndrome (PCOS) to assess its predisposition to menstrual dysregulation post-vaccine. Similarly, contraceptives and period blockers were included to assess the relationship between hormonal disturbances or therapy and menstrual changes post-vaccine. For both contraceptives and period blockers, a yes/no question followed by short answer questions to determine the type and frequency of use were provided. Women who had missing or incomplete answers were excluded from the final analysis (n = 5).
The questionnaire was designed to be self-administered, only accessible once per respondent, and with no time restrictions. To enhance accessibility and accommodate diverse language preferences, the questionnaire was thoughtfully translated into both Arabic and English. Our recruitment efforts began on social media sites such as Twitter and Instagram. In addition, we utilized WhatsApp groups, including the friends and family groups, initially to share the online survey link. Participants were encouraged to further share this link with other women. Prior to distribution, a pilot study of the questionnaire was conducted by gathering responses from 45 women. This step allowed for the identification of potential issues in the questionnaire design and ensured that the final questionnaire was well-structured and user-friendly. The questionnaire was checked for content validity by experts in research and women's health, and it was made publicly available for a specified period, from 25 June to 11 August 2022.
Study outcomes
The main outcome of this study was the presence of perceived menstrual changes, as measured by four criteria: regularity, spotting between cycles, volume of bleeding per cycle, and pain. 13 A menstrual cycle is considered regular if bleeding occurs every 28 days on average, however the length of a cycle can range from 21 to 35 days. We defined change in regularity as perceived delay or early bleeding in a previously predictable cycle. Dysmenorrhea is painful menstruation. The term comes from the Greek “dys” meaning difficult, “meno” meaning monthly, “rhea” meaning flow. Contextually, we defined change in dysmenorrhea as perceived change in the severity of the individual’s pain (whether it became milder or more severe) from their personal baseline. Intermenstrual bleeding is abnormal bleeding or spotting between menstrual cycles. Contextually, we defined this as new onset, increased, or decreased frequency of bleeding between cycles. We used the terms “intermenstrual bleeding” and “spotting” interchangeably in this text. Flow volume was subjectively determined by each individual. Change in volume was dependent on personal perceptions of lighter or heavier bleeding compared to individuals’ personal baselines.
Statistical analysis
Categorical variables were summarized as frequency (percentage) and numerical variables as mean and standard deviation (SD). The chi-square test was used to examine the association between categorical variables, and the t-test was used for numerical variables. Multiple logistic regression was conducted separately for each outcome to determine the variables independently associated with change. Odds ratios (ORs), and the related 95% confidence interval (CI), were reported. A p-value of < 0.05 was considered statistically significant. The statistical analysis was performed using JMP Pro 14 software (JMP, Pro 14; SAS Institute Inc., Cary, NC, 1989–2019).
Results
Demographics
A total of 385 women responded to our survey, of whom two did not consent to participate; thus, the analysis included the remaining 383 consenting participants—45 (11.75%) of whom were the respondents in the pilot study. All respondents participated voluntarily and did not receive any compensation in return. The mean age of the women in our study was 35 ± 10 years. Half of them were either unemployed or educators, and the other half were students, healthcare workers, managers, sales workers, social workers, or retirees, in descending order. About 95% of our responders were Saudis and the remaining 5% were of different nationalities. All 383 were residents of Saudi Arabia, as per the inclusion criteria. The majority of participants lived in the western and northern regions of the country, while the rest were scattered across the eastern, central, and southern regions.
COVID-19 history and vaccines
Of all 383 participants, 232 (60.57%) denied ever contracting the COVID-19, whereas 151 (39.43%) had contracted it at some point since the beginning of the pandemic in March 2020, as documented by a nasal or throat swab test results. All the participants had received at least one dose of any COVID-19 vaccine, with a mean of 3 ± 0.5 doses. The number of doses was otherwise irrelevant as the objective of the question is to assert each participant received at least one dose. Majority of the participants (64.23%) had received the Pfizer-BioNTech vaccine or a combination of the Pfizer-BioNTech vaccine and AstraZeneca or Moderna vaccines. Few participants had received only the AstraZeneca (7.05%) or only the Moderna (0.26%) vaccines. A total of 179 participants were vaccine skeptics (see Table 1).
Demographics, COVID-19 history, vaccine dose and type, and sexual history.
SD: standard deviation; PCOS: polycystic ovarian syndrome.
Sexual history
Table 1 shows that a majority (62.66%) of the participants were sexually active and a majority (79.90%) denied using any contraceptives, while 20.10% reported the use of some form of contraception such as oral contraceptive pills (OCPs), intrauterine devices (IUDs), condoms, patches, subdermal contraceptive implants, coitus interruptus, vaginal rings, or contraceptive injections. Non-hormonal contraceptives (condoms and coitus interruptus) were excluded from the analysis. Only about a third (31.33%) of the participants said they had used oral period-blocking pills, either with or without a proper prescription. Only 12.27% reported having been diagnosed with PCOS prior to receiving any doses of COVID-19 vaccine.
Vaccine and menstruation
Figures 1–4 illustrate the menstrual cycle activity exhibited by all participants before and after at least one dose of a COVID-19 vaccine, as regularity, flow volume, dysmenorrhea, and intermenstrual bleeding, respectively. The results showed an increase in the percentage of women experiencing alterations in their regularity, shifting toward the “not very regular/irregular” cycle post-vaccine (p < 0.001). A notable increase was seen in instrumental bleeding post-vaccine (60%) compared to pre-vaccine (40%; p = 0.008). In addition, more women reported extreme dysmenorrhea post-vaccine compared to pre-vaccine (p < 0.001). Figure 5 shows that results of the directions of change in flow volume reported by participants are almost equal; 38% reported a change from normal to scanty flow volume, while 40% reported a change from normal to heavy flow volume.
Menstrual cycle regularity before and after at least one dose of COVID-19 vaccines.
Menstrual flow volume before and after at least one dose of COVID-19 vaccines.
Dysmenorrhea before and after at least one dose of COVID-19 vaccines.
Intermenstrual bleeding before and after at least one dose of COVID-19 vaccines.
The direction of change in flow volume post-COVID-19 vaccine.
Using the chi-square test, we measured the association between COVID-19 vaccine administration and menstrual changes to identify the likely associated factors. No statistically significant change in duration of cycle was found (p = 0.57). The findings show that PCOS was significantly associated with an increase in dysmenorrhea post-vaccine (see Table 2). Women without PCOS experienced less change in dysmenorrhea than those with PCOS (23.88% vs 37.78%, p = 0.045). PCOS was not associated with changes in the duration of the cycle, the number of days on which bleeding occurred, or the flow volume of bleeding. On the contrary, period blockers were not associated with any menstrual changes (p > 0.05).
The association between predisposing conditions and menstrual disturbances after COVID-19 vaccine administration.
PCOS: polycystic ovarian syndrome. Chi-square test is used to calculate the p-value.
p < 0.05.
Multiple logistic regression analysis, adjusting for important confounding factors such as age, PCOS, and contraceptive use, identified vaccine skeptics as being significantly and independently associated with perceptions of menstrual change. Skeptics were about three times more likely to perceive changes in regularity post-vaccine than non-skeptics (OR = 2.96, 95% CI = 1.79–4.90, p < 0.001). In addition, a separate multiple logistic regression analysis implemented for change in volume showed that contraceptive use and vaccine skepticism were both independently associated with change in volume. Those on contraceptives were about two times more likely to experience volume changes compared to those not using contraceptives (OR = 2.09, 95% CI = 1.23–3.57, p = 0.006). Vaccine skeptics were about three times more likely to perceive changes in volume following vaccination (OR = 3.04, 95% CI = 1.95–4.74, p < 0.001). Table 3 shows the results of the multiple logistic regression analysis.
Regression analysis for change in regularity and volume.
OR: odds ratio; CI: confidence interval. Only variables independently and significantly associated with change are presented.
Discussion
Pfizer, AstraZeneca, and Moderna claim that the most common side effects of their COVID-19 vaccines are fever, fatigue, headache, body aches, and swelling. However, one of the more frequently discussed side effects of the COVID-19 vaccine among women in the media and in clinics is menstrual dysregulation. Across the globe, women are complaining of delayed or early menstruation, heavier bleeding, increased dysmenorrhea, and breakthrough bleeding after receiving a dose of COVID-19 vaccine.5,11,14 On a physiological level, the menstrual cycle is tightly regulated by the hypothalamus–pituitary–ovarian axis. This axis is very sensitive to internal as well as external stimuli, including social and psychological stressors.
Cortisol is a well-established stress hormone that affects the reproductive organs, inflammation, and immune responses. It has thus been theorized that the desired biological immune response to the messenger RNA (mRNA) vaccine, coupled with the psychological stress of vaccine skepticism and the social stress of providing herd immunity to the vulnerable, might increase cortisol secretion.7,15 In context of the menstrual cycle, cortisol suppresses luteinizing hormone (LH). Suppressed LH results in anovulation disrupting estrogen and progesterone levels; creating a cascade that ends with menstrual dysregulation following vaccination. 5
Taking this into consideration, we surveyed women to assess the extent of post-vaccination menstrual dysregulation and identified the factors associated with that dysregulation. We found that the menstrual cycles of healthy women who had no doubts or misgivings about the vaccine, remained the same after COVID-19 vaccination. These women did not experience significant changes in regularity, volume, dysmenorrhea, or intermenstrual bleeding, or any new onset of dysmenorrhea or intermenstrual bleeding, following vaccination. Their cycles were virtually unchanged. Interestingly, this was not the case for vaccine skeptics. Women who self-identified as vaccine skeptics were found to be three times more likely to report a change in their menstrual cycle, including changes in regularity, volume, and spotting. They perceived changes in three aspects of menstruation out of the four considered in this study; while non-skeptics perceived none. Of all skeptic participants, 64.71% reported no changes in regularity, 32.94% reported a change from regular to irregular menstruation, and 2.35% reported a change from irregular to regular menstruation.
Vaccine skepticism is currently an area of increased interest and ongoing research. It is so rampant that a team of psychologists in Romania developed a new scale to measure COVID-19 vaccine hesitancy. 15 Understanding the psychology behind vaccine skepticism can be complex, especially when most of these individuals are otherwise fully vaccinated and content with all vaccines except those for COVID-19.16,17 By and large, women are reported to be less likely to consider vaccination as the only permanent solution to COVID-19. 17 Researchers argue that vaccine skepticism is largely due to lack of confidence in the vaccines’ effectiveness, concerns about unforeseen effects, belief in the existence of other solutions, the availability of effective medical treatment for those infected, fear of vaccines causing infertility, lack of full Food and Drug Administration (FDA) approval for the vaccines, or that the vaccine is a “big pharma” conspiracy.18 –20 All the aforementioned reasons can be attributed directly to misinformation and/or a lack of proper effective communication from healthcare providers. Moreover, vaccine hesitancy is associated with an increased likelihood of individuals reporting side effects that extend beyond those specifically related to menstruation. 10 When individuals are hesitant about vaccines, they may be more attuned to any changes or discomfort they experience after vaccination, leading them to associate these symptoms with the vaccine.
Other than vaccine skeptics, the only group to report a change in volume was that of women who use hormone-based contraceptives such as OCP or IUD (see Tables 2 and 3). Similarly, women with PCOS prior to receiving the vaccine were more likely to report a slight change in dysmenorrhea than those who did not have PCOS. Our findings align with a previous study that reported higher rates of menstrual disturbances after vaccination among women using OCP or patients with PCOS. 11 These results are to be expected, given that PCOS and contraceptives entail a fragile hormonal balance by definition.21,22 But even then, in spite of these exogenous hormonal influences, reported changes were less severe (i.e. only dysmenorrhea or only volume) than those reported by skeptics. Having said that, COVID-19 vaccines appear to be significantly associated with disturbing the balance of people with a vulnerable hormone balance, that is, those diagnosed with PCOS or those using contraceptives. However, PCOS in and of itself is a risk factor for amenorrhea and dysmenorrhea, so this might be a confounding factor rather than a result.
It is notable that women who reported volume changes were split almost equally between the extreme opposites of the spectrum—those experiencing a change from normal to heavy volume and those reporting a change from normal to scanty volume. Furthermore, while some participants reported prolonged periods of delayed bleeding, others reported increased intermenstrual bleeding. Regarding regularity, a greater number of women reported experiencing a shift to a “not very regular/irregular” menstrual cycle after receiving the COVID-19 vaccine. In Italy, Laganà et al. 8 conducted a study to explore the effects of COVID-19 vaccines on the menstrual cycles of healthy women. They excluded women with preexisting gynecological or non-gynecological conditions, those who were receiving hormonal treatment, and those with irregular menstrual cycles. They found that irregularity in menstruation seems to be slightly higher after the second dose. Most notably, they found that these irregularities appear to be self-resolving within two cycles.
Originally, we hypothesized that oral period-blocking pills might be associated with menstrual disturbances after receiving a COVID-19 vaccine dose; however, the results indicate that there is no relationship between these pills, the vaccine, and menstruation. Age does not appear to play a role either; nor does personal history of contracting the COVID-19. Thus, the major factor associated with menstrual disturbances following COVID-19 vaccination was vaccine skepticism or a preexisting hormonal imbalance prior to receiving any dose of the vaccine.
In this study, we chose not to assess the body mass index (BMI), since previous research had reported no significant association between BMI, COVID-19 vaccine, and menstruation. 14 To ensure the accuracy of our findings, participants were asked to disclose any chronic illnesses they might have had. This step allowed us to identify and exclude individuals with known medical conditions that could impact menstrual patterns, such as uncontrolled hypothyroidism.11,23
Limitations
In the questionnaire, we intentionally omitted the question of whether the change was perceived or documented because we were specifically interested in how vaccine skeptics would answer. Our interest was subjected perception rather than objective reality. We believed that asking for proper documentation might skew the results. That being said, we acknowledge that this may have led to arbitrary answers, resulting in self-reporting bias or recall bias. 24 Prior sample size calculation was not performed; therefore, the study power may not have been adequate. This also highlights a limitation, as the findings may not be generalizable to the broader population.
Conclusion
Our findings suggest that receiving the COVID-19 vaccine while on OCP or IUD is associated with an increase in bleeding volume per cycle and that having PCOS prior to the vaccine is associated with dysmenorrhea after receiving the vaccine. Primarily, vaccine skepticism appears to play the role of a “placebo effect” in changes—or perceived changes—of the menstrual cycle following vaccination, including changes in regularity, volume, and spotting. The vaccine in and of itself is not significantly associated with significant menstrual disturbance in healthy women with no preconceived notions or misgivings about COVID-19 vaccines. This article can be utilized as a guide for conducting future studies on COVID-19 vaccines and their perceived side effects, particularly among vaccine skeptics. Public education and health campaigns by healthcare professionals are key to countering myths and misinformation about COVID-19 vaccines among the general population.
Supplemental Material
sj-docx-1-whe-10.1177_17455057231210094 – Supplemental material for Dysmenorrhea, intermenstrual bleeding, menstrual flow volume changes, and irregularities following COVID-19 vaccination and the association with vaccine skepticism: A retrospective observational study
Supplemental material, sj-docx-1-whe-10.1177_17455057231210094 for Dysmenorrhea, intermenstrual bleeding, menstrual flow volume changes, and irregularities following COVID-19 vaccination and the association with vaccine skepticism: A retrospective observational study by Ghadeer A Khan, Alaa Althubaiti, Amal Alshrif, Zahra Alsayed and Hatim Jifree in Women’s Health
Supplemental Material
sj-docx-2-whe-10.1177_17455057231210094 – Supplemental material for Dysmenorrhea, intermenstrual bleeding, menstrual flow volume changes, and irregularities following COVID-19 vaccination and the association with vaccine skepticism: A retrospective observational study
Supplemental material, sj-docx-2-whe-10.1177_17455057231210094 for Dysmenorrhea, intermenstrual bleeding, menstrual flow volume changes, and irregularities following COVID-19 vaccination and the association with vaccine skepticism: A retrospective observational study by Ghadeer A Khan, Alaa Althubaiti, Amal Alshrif, Zahra Alsayed and Hatim Jifree in Women’s Health
Footnotes
References
Supplementary Material
Please find the following supplemental material available below.
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