Abnormal uterine bleeding during the COVID-19 pandemic: a national survey (preprint)

Objective: To evaluate and characterize menstrual changes among COVID-19 vaccinated and infected women. Design A national survey. Setting An online nationwide questionnaire survey, querying about menstrual changes after COVID-19 vaccination or infection. Population Reproductive-age non-pregnant women. Methods The questionnaire was distributed via an online link through social media and directed the participants to an online anonymous Google questionnaire. Results In total, 10,319 women responded, of which 7,904 met the inclusion criteria. Changes in menstrual patterns following the BNT162b2 vaccine were reported by 3,689 (46.7%). Of these, 2,974 women, (80.6%) described excessive bleeding (heavy, prolonged, or intermenstrual) compared with 715 (19.4%) who reported scant bleeding (light, short, or prolonged intervals). Among women who experienced abnormal uterine bleeding (AUB), in most cases (61.1%) it occurred between the vaccination and the ensuing menstrual period. Menstrual disturbances were more common among accurately vaccinated women compared with inaccurately vaccinated by having received a single shot or having undergone a prolonged interval between shots (51% vs 36.6%, P < .001). Menstrual disturbances were similar in type and distribution among the vaccinated and infected women. Conclusions AUB emerged as a side effect of the BNT162b2 vaccine and a symptom of the COVID-19 infection. It was characterized mainly by excessive bleeding. Although the precise incidence could not be determined in this study, the type of bleeding disturbance, as well as the characterization of women at risk, were well defined. The incidence and the long-term consequences of the BNT162b2 vaccine on uterine bleeding warrant further investigation.

Menstrual-Related Disturbances Following SARS-CoV-2 Vaccination: A Spanish Retrospective Observational Study in Formerly Menstruating Women (preprint)

To date, the impact of COVID-19 vaccination on formerly menstruating women remains unknown. For this reason, a retrospective observational cross-sectional study was conducted (N= 548) using an online survey. General characteristics, medical history, and adverse events following COVID-19 vaccination were recorded. In comparison with the first dose, significantly higher percentages of respondents experienced menstrual-related disturbances (dose 1: 38.5% vs. dose 2: 44.8%; McNemar=9.15; mid P-value=0.002), as well as the simultaneous occurrence of two or more of these symptoms (dose 1: 11.2% vs. dose 2: 15.3%; McNemar=13.53; mid P-value=0.044) after receiving the second one. Among them, those related with the length and flow stand out, being of long-term nature in about 17-20% of cases. Interindividual factors influencing this unexpected event after receiving the dose 1 may include weight (AOR 1.02, CI 95% 1.01–1.03, P<.001), perimenopause (AOR 2.28, CI 95% 1.37–3.77, P=.001), pre-existing diagnoses of non-autoimmune rheumatic/articular conditions (AOR 0.31, CI 95% 0.10–1.00, P=0.05), hormonal contraceptive use (AOR 0.25, CI 95% 0.07-0.82, P=0.02), suffering from other vaccine side effects − such as arm pain (AOR 0.61, CI 95% 0.39–0.95, P=0.03), headache (AOR 0.53, CI 95% 0.35 – 0.80, P=.003), swollen glands (AOR 0.29, CI 95% 0.15 – 0.60, P=.001) and nauseas (AOR 0.35, CI 95% 0.14 – 0.86, P=0.02) – and the number of previous pregnancies (AOR 2.70, CI 95% 1.54 – 4.76, P=.001). Formerly menstruating women may experience long-term menstrual-related disturbances following COVID-19 vaccination.

COVID-19 Disease and Menstrual-Related Disturbances: A Spanish Retrospective Observational Study in Formerly Menstruating Women (preprint)

After three years of the onset of the pandemic, there is scarce evidence about how COVID-19 disease affect the female reproductive system, and consequently, the menstrual cycle. Since the common causes of secondary amenorrhea are considered as exclusion criteria in the studies about menstrual changes following SARS-CoV-2 infection, the prevalence of this event and the influencing factors in formerly menstruating women remains unknown. A retrospective observational cross-sectional study was conducted on Spanish adult women (N= 17,512), using an online survey; a subpopulation of SARS-CoV-2-infected-formerly menstruating women was included in the present analysis (n= 72). Collected data included general characteristics, medical history, and specific information about COVID-19 disease. 38.9% of the respondents experienced menstrual-related disturbances after suffering from the COVID-19 disease, unexpected vaginal bleeding being the most common (20.8%). Other alterations related with the length – “shorter” by 12.5% − and the flow − “heavier than usual” 30.3% − of the menstrual bleeding were reported. The binary logistic regression showed that being a perimenopausal woman (AOR 4.608, CI 95%, 1.018 – 20.856, p = 0.047) and having heavy menstrual bleeding (AOR 4.857, CI 95%, 1.239 – 19.031, p=0.023) are influential factors. This evidence could help health professionals to provide scientifically up-to-date information to their patients, empowering them to actively manage their reproductive health, especially in those societies where menstrual health is still a taboo.

Association between SARS-CoV-2 vaccination and healthcare contacts for menstrual disturbance and bleeding in women before and after menopause: nationwide, register based cohort study.

OBJECTIVES: To evaluate the risks of any menstrual disturbance and bleeding following SARS-CoV-2 vaccination in women who are premenopausal or postmenopausal. DESIGN: A nationwide, register based cohort study. SETTING: All inpatient and specialised outpatient care in Sweden from 27 December 2020 to 28 February 2022. A subset covering primary care for 40% of the Swedish female population was also included. PARTICIPANTS: 2 946 448 Swedish women aged 12-74 years were included. Pregnant women, women living in nursing homes, and women with history of any menstruation or bleeding disorders, breast cancer, cancer of female genital organs, or who underwent a hysterectomy between 1 January 2015 and 26 December 2020 were excluded. INTERVENTIONS: SARS-CoV-2 vaccination, by vaccine product (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 (AZD1222)) and dose (unvaccinated and first, second, and third dose) over two time windows (one to seven days, considered the control period, and 8-90 days). MAIN OUTCOME MEASURES: Healthcare contact (admission to hospital or visit) for menstrual disturbance or bleeding before or after menopause (diagnosed with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes N91, N92, N93, N95). RESULTS: 2 580 007 (87.6%) of 2 946 448 women received at least one SARS-CoV-2 vaccination and 1 652 472 (64.0%) 2 580 007 of vaccinated women received three doses before the end of follow-up. The highest risks for bleeding in women who were postmenopausal were observed after the third dose, in the one to seven days risk window (hazard ratio 1.28 (95% confidence interval 1.01 to 1.62)) and in the 8-90 days risk window (1.25 (1.04 to 1.50)). The impact of adjustment for covariates was modest. Risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with BNT162b2 and mRNA-1273 after the third dose, but the association with ChAdOx1 nCoV-19 was less clear. For menstrual disturbance or bleeding in women who were premenopausal, adjustment for covariates almost completely removed the weak associations noted in the crude analyses. CONCLUSIONS: Weak and inconsistent associations were observed between SARS-CoV-2 vaccination and healthcare contacts for bleeding in women who are postmenopausal, and even less evidence was recorded of an association for menstrual disturbance or bleeding in women who were premenopausal. These findings do not provide substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.

Menstrual cycle disturbances after COVID-19 vaccination.

INTRODUCTION: After COVID-19 vaccination, women of reproductive age reported changes in their menstrual cycle. MATERIALS AND METHODS: A retrospective study was carried out after a survey on social networks that included women aged 18-41 years with normal cycles according to International Federation of Gynecology and Obstetrics and who were vaccinated (complete schedule for two doses, except J&J/Janssen or incomplete with a single dose). Women with following conditions were excluded: pregnant or lactating women; history of diseases that cause menstrual irregularities or early menopause: anorexia, bulimia, polycystic ovary syndrome, hypothyroidism, obesity, or low weight; hysterectomized or oophorectomized patients; and high performance athletes. RESULTS: Overall, 950 women completed the survey between July and September 2021. In total, 408 women met the inclusion criteria, and 184 reported the following characteristics: frequency (normal 43.47%, infrequent 25%, and frequent 31.53%), regularity (regular 51.08%, irregular 42.93%, and absent/amenorrhea 5.97%), duration (normal 65.21%, prolonged 26.08%, absent/amenorrhea 8.69%), and volume (heavy 41.84%, light 20.65%, and absent/amenorrhea 6.52%). CONCLUSIONS: SARS-CoV-2 infection and COVID-19 vaccination can influence the menstrual cycle and cause alterations.

Impact of the COVID-19 pandemic on young people with and without pre-existing mental health problems.

The objective was to examine pandemic-related changes in depression and anxiety symptoms in adolescents and young adults in Germany considering pre-existing depression and anxiety problems. In this cross-sectional study, 11,523 adolescents and young adults aged 14-21 years who perceived an impact of the Coronavirus disease (COVID-19) pandemic on their mental health reported the frequencies of depression and anxiety symptoms retrospectively for different pre-pandemic and pandemic phases. Data were collected using web-based questionnaires between January 5th and February 20th, 2022. Depression and anxiety were assessed with a modified version of the Patient Health Questionnaire (PHQ-4). Scale-fit cut-offs were used to identify pre-existing elevated depression and anxiety scores. Multilevel mixed linear models were conducted to assess changes in depression and anxiety symptoms from 2019 to 2021 and compare for age, gender and pre-pandemic mental health problems. Among young people who were experiencing mental health changes as a result of the pandemic, the frequency of depression and anxiety symptoms increased during the COVID-19 pandemic. This association was moderated by age, gender, and pre-existing elevated depression/anxiety scores. For young people without elevated pre-pandemic depression/anxiety, the scores increased strongly over time, with 61% reporting elevated depression symptoms and 44% reporting elevated anxiety symptoms in 2021. In contrast, self-perceived change was minimal for adolescents and young adults with elevated pre-pandemic depression and anxiety. Among young people whose mental health has been affected by the COVID-19 pandemic, the group without pre-pandemic mental health conditions reported greater deterioration than those with elevated pre-pandemic depression and anxiety scores. Thus, adolescents and young adults without pre-existing depression and anxiety problems who perceived a change in general mental health due to the pandemic reported an alarming increase in symptoms of depression and anxiety during the COVID-19 pandemic period.

The COVID-19 vaccines and menstrual disorders.

OBJECTIVE: The COVID-19 vaccination has been linked to numerous reports of menstrual disorders as potential side effects. However, menstrual cycle results after vaccination were not collected throughout clinical trials. According to other research, COVID-19 vaccination and menstrual disorders have no discernible connection, and menstrual disorders are temporary. SUBJECTS AND METHODS: We asked questions about menstruation disturbances following the first and second doses of the COVID-19 vaccine in a population-based cohort of adult Saudi women to determine whether the vaccination is linked to menstrual cycle irregularities. RESULTS: According to the results, 63.9% of women experienced variations in their menstrual cycle either after the first or second dose. Such results show that COVID-19 vaccination impacts women's menstrual cycles. However, there is no need for concern because the alterations are relatively minor, and the menstrual cycle usually returns to normal within two months. Additionally, there are no obvious distinctions between the various vaccine types or body mass. CONCLUSIONS: Our findings support and explain the self-reports of menstrual cycle variations. We have discussed reasons for these problems that describe the mechanism of the relationship between them and the immune response. Such reasons will help prevent hormonal imbalances and the influence of therapies and immunizations on the reproductive system.

COVID-19 vaccination and menstrual disorders among women: Findings from a meta-analysis study.

BACKGROUND: COVID - 19 vaccine can lead to various local and systemic side effects, including menstrual irregularities in women. There is no robust quantitative evidence of the association between the COVID - 19 vaccine and menstrual irregularities. A meta-analysis was performed to estimate the pooled prevalence of a range of menstrual disorders that may occur in women following COVID - 19 vaccination. METHODS: After searching for epidemiological studies, we systematically performed a meta-analysis on PubMed/Medline, EMBASE, and Science Direct. Sixteen studies were finally included in the study. We estimated the pooled prevalence and corresponding 95 % confidence intervals (CIs) for a group of menstrual disorders, including menorrhagia, polymenorrhea, abnormal cycle length, and oligomenorrhea. Heterogeneity was assessed using the I2 statistic and the Q test. RESULTS: Overall, the pooled prevalence of menorrhagia was 24.24 % (pooled prevalence 24.24 %; 95 % CI: 12.8-35.6 %). The pooled prevalence of polymenorrhea was 16.2 % (pooled prevalence: 16.2 %; 95 % CI: 10.7-21.6 %). The pooled prevalence of abnormal cycle length was relatively lower than that of the other disorders (pooled prevalence: 6.6 %; 95 % CI: 5.0-8.2 %). The pooled prevalence of oligomenorrhea was 22.7 % (95 % CI: 13.5-32.0 %). CONCLUSION: The findings indicate that menorrhagia, oligomenorrhea, and polymenorrhea were the most common menstrual irregularities after vaccination. The findings also suggest that a relatively high proportion of women suffer from menstrual irregularities. Further longitudinal studies are needed to confirm the causal relationship between COVID-19 vaccination and menstrual irregularities.

The association of three doses of the BNT162b2 mRNA vaccine with abnormal bleeding and an irregular menstrual cycle among premenopausal females: A single institute observation study.

BACKGROUND: The COVID-19 vaccine is effective in preventing severe cases of COVID-19. For women, gynecological adverse events, such as menstrual irregularities and irregular bleeding, could be a concern after COVID-19 vaccination. In this study, we investigated gynecological adverse events in the vaccinated Japanese female population. METHODS: We conducted a survey-based study with health-care workers, including medical doctors and nurses, medical coworkers, and medical university faculty, staff, and students, at a single medical school and affiliated hospital in Japan. We used McNemar's test and network analysis. RESULTS: Overall, we obtained 819 responses, and 424 were from females. After the exclusion of contradictory answers, 309 surveys were finally considered appropriate for the analysis. The frequencies of abnormal bleeding were 0.6%, 1.0%, and 3.0% for the first, second, and third doses, respectively. An irregular menstrual cycle was more common than abnormal bleeding: 1.9%, 4.9%, and 6.6% for the first, second, and third doses, respectively. Network analysis revealed that abnormal bleeding and an irregular menstrual cycle were not associated with other adverse reactions. CONCLUSION: The present study showed that the effects of COVID-19 vaccination on menstruation seem limited.

COVID-19 Vaccines: The Impact on Pregnancy Outcomes and Menstrual Function (preprint)

Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.

Menstrual, fertility and psychological impacts after uterine compression sutures for postpartum hemorrhage: a prospective cohort study (preprint)

Background Uterine compression suture is an important conservative surgical technique in managing atonic postpartum hemorrhage. In this study, we aim to evaluate the subsequent menstrual, fertility and psychological outcomes after uterine compression sutures.Methods This was a prospective cohort study between 2009 and 2022 conducted in a tertiary obstetric unit (6000 deliveries per year) in Hong Kong SAR. Women with primary postpartum hemorrhage successfully treated with uterine compression sutures were followed-up in postnatal clinic for two years after delivery. Data on menstrual pattern were collected during each visit. Psychological impact after uterine compression suture was assessed using a standardized questionnaire. Subsequent pregnancies were identified by territory-wide computer registry and telephone interviews. Women with postpartum hemorrhage treated with uterotonic agents only were chosen as controls.Results In our cohort (n = 80), 87.9% of women had return of menses within six months after delivery. Regular monthly cycle was observed in 95.6% of women. Majority of women reported similar menstrual flow (75%), menstrual days (85.3%) and no change in dysmenorrhea status (88.2%) as compared before. Among eight (11.8%) women who reported hypomenorrhea after uterine compression sutures, two cases of Asherman’s syndrome were diagnosed. Among 23 subsequent pregnancies (16 livebirths), no significant differences in outcome were observed except more omental or bowel adhesions (37.5% vs 8.8%, p = 0.007), recurrence of hemorrhage (68.8% vs 7.5%, p < 0.001) and repeated compression sutures (12.5% vs 0%, p = 0.024) were seen in women with previous compression sutures. Over half of the couple declined future fertility after uterine compression sutures with 38.2% of women recalled unpleasant memories and 22.1% reported life-long adverse impact especially tokophobia.Conclusion Majority of women with history of uterine compression sutures had similar menstruation and pregnancy outcomes as compared to those who did not have sutures. However, they had higher intrapartum risk of visceral adhesions, recurrence of hemorrhage and repeated compression sutures next pregnancy. Furthermore, couple could be more susceptible to negative emotional impact.

Infection with SARS-CoV-2 is associated with menstrual irregularities among women of reproductive age.

BACKGROUND: Biological and psychological mechanisms may be responsible for menstrual irregularities occurring among women during the COVID-19 pandemic. STUDY DESIGN: From January 2019 to September 2021, women (18- to 45-years-old and not using hormonal contraception) were recruited in Miami-Dade County, Florida. Cross-sectional, self-report surveys collected data on menstrual irregularities, COVID-19 vaccination, stress, depression, and loneliness. A EUA approved rapid test assay using whole blood measured SARS-CoV-2 IgG antibodies. Chi-square and Fisher's exact tests described menstrual irregularities among women recruited before versus after the start of the COVID-19 pandemic and with detectable versus undetectable SARS-CoV-2 IgG antibodies. A logistic regression examined the relationship between the presence of SARS-CoV-2 IgG antibodies and menstrual irregularities controlling for age, stress, depression, and loneliness. RESULTS: Among 182 women enrolled, 73 were enrolled after pandemic onset, and 36 provided vaccination data. Having detectable SARS-CoV-2 IgG antibodies was associated with a higher percentage of menstrual irregularities among unvaccinated women (0% vs. 39%, p = .026) and among all women regardless of vaccination status (31% vs. 5%; p = .005). Adjusting for age and psychological variables, the odds of menstrual irregularities were 7.03 times (95% CI [1.39, 35.60]; p = .019) higher among women with detectable antibodies compared to women without detectable antibodies. Neither enrollment date, age, nor psychological factors were associated to menstrual irregularities. CONCLUSIONS: Biological mechanisms related to SARS-CoV-2 infection may be responsible for irregular menstruation and should be further examined to mitigate the impact of the COVID-19 pandemic on women's health.

Web and social media searches highlight menstrual irregularities as a global concern in COVID-19 vaccinations.

Delineation of public concerns that prevent vaccine compliance is a major step in generating assurances and enhancing the success of COVID-19 prevention programs. We therefore sought to identify public concerns associated with COVID-19 vaccines, as reflected by web and social media searches, with a focus on menstrual irregularities. We used trajectory analyses of web and social media search data in combination with global COVID-19 data to reveal time-dependent correlations between vaccination rates and the relative volume of vaccine and period related searches. A surge of period and vaccine related Google searches followed the introduction of Covid vaccines around the world, and the commencement of vaccination programs in English speaking countries and across the United States. The relative volume of searches such as "Covid vaccine menstrual irregularities", "Covid vaccine menstrual period", "Pfizer vaccine menstruation", and "Moderna vaccine menstruation" was each significantly correlated with vaccination rates (Spearman r = 0.42-0.88, P = 4.33 × 10-34-1.55 × 10-5), and significantly different before and after the introduction of Covid vaccines (Mann-Whitney P = 2.00 × 10-21-7.10 × 10-20). TikTok users were more engaged in period problems in 2021 than ever before. International, national, and state-level correlations between COVID-19 vaccinations and online activity demonstrate a global major concern of vaccine-related menstrual irregularities. Whether it is a potential side effect or an unfounded worry, monitoring of web and social media activity could reveal the public perception of COVID-19 prevention efforts, which could then be directly addressed and translated into insightful public health strategies.

COVID-19 vaccine and menstrual conditions in female: data analysis of the Vaccine Adverse Event Reporting System (VAERS).

BACKGROUND: In reports of adverse reactions following vaccination with the coronavirus disease 2019(COVID-19) vaccines, there have been fewer reports of concern for menstrual disorders in female. OBJECTIVE: Our study employed Vaccine Adverse Event Reporting System (VAERS) to investigate and analyze the relationship between COVID-19 Vaccines and menstrual disorders in female. METHODS: We collected reports of menstrual disorders in VAERS from July 2, 1990 to November 12, 2021, and performed a stratified analysis. The potential relationship between COVID-19 vaccine and reports of menstrual disorders was evaluated using the Reporting Odds Ratio (ROR) method. RESULTS: A total of 14,431 reports of menstrual disorders were included in the study, and 13,118 were associated with COVID-19 vaccine. The ROR was 7.83 (95% confidence interval [95%CI]: 7.39-8.28). The most commonly reported event was Menstruation irregular (4998 reports), and a higher percentage of female aged 30-49 years reported menstrual disorders (42.55%) after exposure to COVID-19 Vaccines. Both for all reports of menstrual disorders (ROR = 5.82; 95%CI: 4.93-6.95) and excluding reports of unknown age (ROR = 13.02; 95%CI: 10.89-15.56),suggest that female age may be associated with menstrual disorders after vaccination with the COVID-19 Vaccines. CONCLUSION: There is a potential safety signal when the COVID-19 vaccine is administered to young adult female (30-49 years old), resulting in menstrual disorders in. However, due to the well-known limitations of spontaneous reporting data, it is challenging to explicity classify menstrual disorders as an adverse event of the COVID-19 Vaccines, and reports of adverse reactions to COVID-19 Vaccines in this age group should continue to be tracked.

Menstrual irregularities and vaginal bleeding after COVID-19 vaccination reported to v-safe active surveillance, USA in December, 2020-January, 2022: an observational cohort study.

BACKGROUND: Anecdotal reports of menstrual irregularities after receiving COVID-19 vaccines have been observed in post-authorisation and post-licensure monitoring. We aimed to identify and classify reports of menstrual irregularities and vaginal bleeding after COVID-19 vaccination submitted to a voluntary active surveillance system. METHODS: This observational cohort study included recipients of a COVID-19 vaccine who were aged 18 years and older and reported their health experiences to v-safe, a voluntary smartphone-based active surveillance system for monitoring COVID-19 vaccine safety in the USA, from Dec 14, 2020, to Jan 9, 2022. Responses to survey questions on reactions after vaccination were extracted, and a pre-trained natural language inference model was used to identify and classify free-text comments related to menstruation and vaginal bleeding in response to an open-ended prompt about any symptoms at intervals after vaccination. Related responses were further categorised into themes of timing, severity, perimenopausal and postmenopausal bleeding, resumption of menses, and other responses. We examined associations between symptom theme and respondent characteristics, including vaccine type and dose number received, solicited local and systemic reactions reported, and health care sought. FINDINGS: 63 815 respondents reported on menstrual irregularities or vaginal bleeding, which included 62 679 female respondents (1·0% of 5 975 363 female respondents aged ≥18 years). Common themes identified included timing of menstruation (70 981 [83·6%] responses) and severity of menstrual symptoms (56 890 [67·0%] responses). Other themes included menopausal bleeding (3439 [4·0%] responses) and resumption of menses (2378 [2·8%] responses). Respondents submitting reports related to menopausal bleeding were more likely to seek health care than were those submitting reports related to other menstruation and vaginal bleeding themes. INTERPRETATION: Reports of heterogeneous symptoms related to menstruation or vaginal bleeding after COVID-19 vaccination are being submitted to v-safe, although this study is unable to characterise the relationship of these symptoms to COVID-19 vaccination. Methods that leverage pretrained models to interpret and classify unsolicited signs and symptoms in free-text reports offer promise in the initial evaluation of unexpected adverse events potentially associated with use of newly authorised or licensed vaccines. FUNDING: Centers for Disease Control and Prevention.

The effects of obesity on the menstrual cycle.

The prevalence of childhood and adolescent obesity has significantly increased in the United States and worldwide since the 1970s, a trend that has been accelerated by the COVID-19 pandemic. The complications of obesity range from negative effects on the cardiovascular, endocrine, hepatobiliary, and musculoskeletal systems to higher rates of mental health conditions such as depression and eating disorders among affected individuals. Among adolescent girls, childhood obesity has been associated with the earlier onset of puberty and menarche, which can result in negative psychosocial consequences, as well as adverse effects on physical health in adulthood. The hormones leptin, kisspeptin and insulin, and their actions on the hypothalamic-pituitary-ovarian axis, have been implicated in the relationship between childhood obesity and the earlier onset of puberty. Obesity in adolescence is also associated with greater menstrual cycle irregularity and the polycystic ovary syndrome (PCOS), which can result in infrequent or absent menstrual periods, and heavy menstrual bleeding. Hyperandrogenism, higher testosterone and fasting insulin levels, and lower levels of sex hormone-binding globulin, similar to the laboratory findings seen in patients with PCOS, are also seen in individuals with obesity, and help to explain the overlap in phenotype between patients with obesity and those with PCOS. Finally, obesity has been associated with higher rates of premenstrual disorders, including premenstrual syndrome and premenstrual dysphoric disorder, and dysmenorrhea, although the data on dysmenorrhea appears to be mixed. Discussing healthy lifestyle changes and identifying and managing menstrual abnormalities in adolescents with obesity are key to reducing the obstetric and gynecologic complications of obesity in adulthood, including infertility, pregnancy complications, and endometrial cancer.