Bloody stressed! A systematic review of the associations between adulthood psychological stress and menstrual cycle irregularity.

Regular menstruation is a key indicator of general health and irregular menstrual parameters have been associated with elevated risk of adverse health outcomes. While psychological stress is believed to contribute to abnormal menstruation, little is known of the effects of discrete psychological stressors, including the COVID-19 pandemic, on menstrual function. A systematic database search was performed and studies investigating the relation between psychological stress and menstrual cycle irregularity in otherwise healthy adults were included. Two independent investigators completed abstract and full-text screening, data extraction, and risk of bias assessment. In the 41 included studies, a variety of stressors were assessed, namely COVID-19 pandemic stress, academic stress, and occupational stress. Our review found most studies report an association between psychological stress and menstrual dysfunction, with the most common disruptions being irregular menstruation and abnormal menstrual flow. Our findings also underlined notable discrepancies in the operational definitions used in the study of menstrual disorders. These observations emphasize the importance of psychological stress as a modifiable risk factor associated with irregular menstruation.

A cross-sectional study confirms temporary post-COVID-19 vaccine menstrual irregularity and the associated physiological changes among vaccinated women in Jordan.

Background: COVID-19 vaccines continue to save people's lives around the world; however, some vaccine adverse events have been a major concern which slowed down vaccination campaigns. Anecdotal evidence pointed to the vaccine effect on menstruation but evidence from the adverse event reporting systems and the biomedical literature was lacking. This study aimed to investigate the physiological changes in women during menstruation amid the COVID-19 vaccination. Methods: A cross-sectional online survey was distributed to COVID-19 vaccinated women from Nov 2021 to Jan 2022. The results were analyzed using the SPSS software. Results: Among the 564 vaccinated women, 52% experienced significant menstrual irregularities post-vaccination compared to before regardless of the vaccine type. The kind of menstrual irregularity varied among the vaccinated women, for example, 33% had earlier menstruation, while 35% reported delayed menstruation. About 31% experienced heavier menstruation, whereas 24% had lighter menstrual flow. About 29% had menstruation last longer, but 13% had it shorter than usual. Noteworthy, the menstrual irregularities were more frequent after the second vaccine shot, and they disappeared within 3 months on average. Interestingly, 24% of the vaccinated women reported these irregularities to their gynecologist. Conclusion: The COVID-19 vaccine may cause physiological disturbances during menstruation. Luckily, these irregularities were short-termed and should not be a reason for vaccine hesitancy in women. Further studies are encouraged to unravel the COVID-19 vaccine adverse effect on women's health.

The Effect of COVID-19 Vaccine on Women's Reproductive Health: A Cross-Sectional Study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) vaccine was developed to stimulate acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms of reproductive health abnormalities have been reported following the administration of the adenovirus and mRNA-containing vaccine. Such complaints included irregular menstrual cycles, miscarriages, changes in sexual interest, vaginal bleeding, and decreased milk supply in breastfeeding mothers. This study aimed to explore the effect of the COVID-19 vaccine on the reproductive health of women attending five primary healthcare centers in the western region of Saudi Arabia. METHODS: A cross-sectional study was conducted with 300 women between 15 and 50 years. Five primary healthcare centers were included from May to September 2022. Non-probability convenient sampling technique was used; data were collected via a self-administered questionnaire from women who received any number or type of COVID-19 vaccine. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 22 (IBM SPSS Statistics, Armonk, NY, USA). RESULTS: Of those who responded to the questionnaire (297 participants), 74% were married, and 52% had 1-3 children. Of the pregnant women, only 4% lost their pregnancy. In addition, of the breastfeeding mothers, 10% noticed a decrease in milk production after the vaccination. The effect of the vaccination status on decreased libido was 11%. A small proportion (18%) of the participants reported worsening dietary habits after the vaccine. Less than half of the participants (44%) reported a change in the length and amount of the menstrual cycle, and 29% worsened premenstrual syndrome (PMS). There was no significant association between the type and the number of doses on the rate of miscarriage (p=0.47), breastmilk production (p=0.47), libido (p=0.11), health diet habits (p=0.15), monthly cycle (p=0.570), heavy menses (p=0.999), and PMS symptoms in the study participants. CONCLUSION: COVID-19 vaccination remains necessary to prevent severe infection and is safe for females of reproductive age, whether trying to get pregnant or lactating, and has no significant effect on the menstrual cycle. This research can be used as a basis when deciding on vaccines in case of future pandemics and remove misinformation and doubts regarding the vaccines that should be adequately addressed.

Assessing Menstrual Changes Among Young Indian Females Post-SARS-CoV-2 Vaccination.

Background The rollout of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has significantly enhanced immunity against coronavirus disease 2019 (COVID-19), leading to a reduction in the severity of illness, hospitalizations, and deaths. While various side effects of the vaccine have been reported, its impact on the menstrual cycle remains unclear. Methods We conducted a cross-sectional study involving university students who had received either partial or full vaccination against SARS-CoV-2. Data was gathered through a questionnaire designed to assess the relationship between menstrual changes and the SARS-CoV-2 vaccination. Results A total of 773 participants, with a mean age of 20.6 ± 1.7 years, were included in this study. The participants reported a significant increase in the irregularity of the menstrual cycle. We observed a slight increase in the length of the menstrual cycle, from 30.0 ± 4.0 days (pre-vaccination) to 30.5 ± 5.6 days (post-vaccination), which was statistically significant (p<0.001). The duration of menstruation also increased, from 4.9 ± 1.7 days (pre-vaccination) to 5.0 ± 1.7 days (post-vaccination). However, this increase in menstrual length due to vaccination was not statistically significant (p = 0.898). Notably, there was a significant increase in pain reported by the participants after receiving the SARS-CoV-2 vaccine (p = 0.004). Conclusion The SARS-CoV-2 vaccination significantly impacted the regularity of the menstrual cycle, length of the menstrual cycle, and pain during menstruation, though temporarily. Our study found no significant differences in menstrual changes or the type of vaccine administered (Covishield and Covaxin).

Anti-Müllerian hormone has limited ability to predict fecundability in Chinese women: a preconception cohort study.

RESEARCH QUESTION: Can anti-Müllerian hormone (AMH) level predict female fecundity in healthy reproductive-aged Chinese women? DESIGN: Preconceptional couples (n = 993) attempting pregnancy without contraception provided information on serum AMH concentrations and essential covariates. They were followed up for 12 months or until a clinically recognized pregnancy occurred between August 2013 and April 2015. Fecundability was indirectly assessed by time-to-pregnancy, defined as the number of menstrual cycles taken to conceive by a sexually active couple without using birth control. Discrete-time Cox proportional hazards model was used to estimate fecundability ratios in relation to AMH levels. Potential effect modifications by woman's age, BMI and menstrual cycle irregularity were examined through stratified analyses. Restricted cubic splines were applied to model the potential non-linear relationship between AMH and fecundability. RESULTS: After adjusting for woman's age, BMI, education status, smoking status, alcohol consumption and parity, AMH level (either as a continuous or categorical variable) was not significantly associated with fecundability. Stratified analyses revealed that, compared with intermediate AMH level (2.78-6.94 ng/ml), low AMH level (<2.78 ng/ml) was associated with reduced fecundability among women with menstrual cycle irregularity; the estimate did not reach statistical significance (adjusted fecundability ratio 0.43, 95% CI 0.16 to 1.15, P for interaction <0.1). CONCLUSIONS: Serum AMH levels were not associated with fecundability in Chinese women of childbearing age. A suggestive association, however, was observed among women with cycle irregularity. Regular monitoring of AMH in fecundity prediction may be of limited value among healthy reproductive-aged Chinese women.

Association between menstrual cycle irregularity and suicidal ideation among Korean women: Results from the Korea national health and nutrition examination survey (2010-2012).

BACKGROUND: We aimed to evaluate the association between menstrual cycle irregularity and suicidal ideation in Korean women. METHODS: Data on 5,606 women from the 2010-2012 Korea National Health and Nutrition Examination Survey, a population-based cross-sectional study, were included. Menstrual cycle irregularity, suicidal ideation, current occupational status, age at menarche, education level, household income, and marital status were assessed through questionnaires with trained interviewers. A multivariate logistic regression analysis was performed after adjusting for age, socioeconomic status, smoking and drinking status, age at menarche, comorbid diseases, and physical activity. RESULTS: In the multivariate-adjusted models, we found significant associations between menstrual cycle irregularity and suicidal ideation (odds ratio [OR], 95% confidence interval [CI] = 1.44 [1.14-1.82]). This association was particularly noticeable in women aged 12 to 29 years (OR [95% CI] = 1.45 [1.04-2.03]), in those who had menarche at a relatively early age (aged 8-13 years) (OR [95% CI] = 1.60 [1.15-2.23]), and in those who were currently employed (OR [95% CI] = 1.46 [1.05-2.04]). LIMITATIONS: Suicidal ideation was evaluated based on the participants' self-reports, and were therefore subjective in nature. Additionally, due to the cross-sectional design and use of retrospective data, causal relationships could not be drawn. CONCLUSION: Women with irregular menstrual cycles were 1.42 times more likely to have suicidal ideation than those with regular cycles. More attention should be paid to menstrual cycle irregularity when attempting to improve levels of suicidal ideation.

Comparison of Clinical, Metabolic and Hormonal Effects of Metformin Versus Combined Therapy of Metformin With Myoinositol Plus D-Chiro-Inositol in Women With Polycystic Ovary Syndrome (PCOS): A Randomized Controlled Trial.

Objective To compare the effects of metformin alone versus combined therapy of metformin with myoinositol (MI) plus D-chiro-inositol (DCI) in women with polycystic ovary syndrome (PCOS). Materials and methods This is a prospective, non-blinded randomized controlled trial conducted in newly diagnosed PCOS women aged 18 to 45 years. Group I received metformin 500 mg twice a day orally for 6 months while group II received metformin 500 mg twice a day orally along with MI 550 mg plus DCI 150 mg twice daily orally for six months. The primary outcome was a change in clinical, metabolic and hormonal parameters of the two groups from baseline to the end of six months of treatment. Results A total of 72 patients were randomized into two groups of 36 patients each. Statistically, a significant difference was seen in terms of mean global acne score (p=0.004) and cycle regularity (p=0.034) after six months of treatment in group II. A significant difference in values of luteinizing hormone (LH) (p=0.002), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio (p=0.007), mean cholesterol (p=0.040), mean high-density lipoprotein (HDL) (p=0.049), mean low-density lipoprotein (LDL) (p=0.0001) and postprandial insulin (p=0.005) was also seen in group II at the end of treatment duration. No significant difference was seen between the two groups in terms of mean FSH, mean testosterone, mean dehydroepiandrosterone sulfate (DHEAS), mean triglyceride, mean fasting and postprandial blood sugar, fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) index. Conclusion Combined therapy with metformin and MI plus DCI in women with PCOS and insulin resistance seems promising with the need for further studies with a greater sample size to evaluate the efficacy of this treatment.

The impact of COVID-19-related mental health issues on menstrual cycle characteristics of female healthcare providers.

AIM: To investigate the association between menstrual cycle regularity in healthcare providers and COVID-19 pandemic-related anxiety, depression, stress. METHODS: A cross-sectional study was conducted by administrating online questionnaires to female healthcare workers in Turkey. Women aged 18-40 years with regular menstrual cycles for more than 1 year before the beginning of the pandemic were included in the study and they were divided into two groups according to menstrual cycle regularity during the pandemic. The questionnaires included sociodemographic characteristics, medical and reproductive history, lifestyle information of participants, COVID-19 Stress Scales (CSS), and a short version of the Depression Anxiety Stress Scale (DASS-21). RESULTS: A total of 952 women were included in the study, 679 had regular menstrual cycles, and 273 had irregular menstrual cycles. The prevalence of irregular menses among Turkish women healthcare workers aged 18-40 years was 28.7%. The CSS subdimensions and total scores were significantly higher in the irregular menstruation group than in women with regular menstruation (p < 0.001). The DASS-21 depression, anxiety, and stress subdimensions were likewise significantly higher in women with irregular menstruation (p < 0.001). Besides, both the univariable and the multivariable logistic regression results showed the relationship between irregular menstruation and CSS total score. CONCLUSION: The current study showed the association between the COVID-19 pandemic-induced anxiety, perceived stress, depressive symptoms, and increased prevalence of menstrual cycle irregularity among healthcare providers.

The menstrual cycle associated with insomnia in newly employed nurses performing shift work: a 12-month follow-up study.

PURPOSE: This study aimed to investigate whether insomnia among newly-employed shift-working nurses is associated with menstrual cycle irregularity. METHODS: We followed 287 nurses employed between 2015 and 2016 for 12 months. An Insomnia Severity Index (ISI) was completed to determine levels of insomnia 6 months after beginning work. At baseline and at 12-month follow-up, menstrual cycle information was obtained using clinical interviews. We analyzed baseline data separately by prevalence (participants with menstrual irregularity, n = 287) and incidence (participants with no reported menstrual irregularity, n = 238). RESULTS: In a multivariate logistic regression analysis, including age, body mass index, and physical activity, insomnia was associated with a 2.05-fold increase in the odds of newly developing menstrual cycle irregularity compared with not having insomnia [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.12-3.77]. Insomnia was associated with a 3.05-fold increase in the prevalence of menstrual cycle irregularity compared with not having insomnia (OR 3.05, 95% CI 1.81-5.13). As the ISI score increased, both the incidence and prevalence odds of menstrual cycle irregularity tended to increase. CONCLUSIONS: Insomnia can induce menstrual cycle irregularity among nurses working shifts, and insomnia may have an important role in the pathway from shift work to menstrual dysfunction, aside from the possible effects of circadian rhythm disruption.

Mental health, psychotropic medication use, and menstrual cycle characteristics.

PURPOSE: To examine the influence of depressive symptoms, perceived stress, and psychotropic medication use on prospectively assessed menstrual cycle regularity and length. PARTICIPANTS AND METHODS: Data were obtained from Pregnancy Study Online, a prospective cohort study of pregnancy planners from North America. At baseline, women reported information on demographics, anthropometrics, lifestyle, and medical history, including their use of psychotropic medications. They also completed the Major Depression Inventory and the Perceived Stress Scale. Every 8 weeks for up to 12 months or until conception, women completed follow-up questionnaires to assess changes in psychotropic medication use, perceived stress, and menstrual cycle characteristics (ie, cycle regularity and length). Women who completed at least one follow-up questionnaire from 2013 to 2018 (n=3,346) were included in the primary analyses. A total of 5,439 women were included in secondary analyses utilizing baseline data only. Primary analyses estimated prevalence ratios (PR) and 95% CIs using log-binomial regression models. RESULTS: Women with severe depressive symptoms at baseline, regardless of psychotropic medication use, had an 80% greater prevalence of irregular cycles during follow-up than women with no or low depressive symptoms (PR =1.80, 95% CI =1.48-2.19). Perceived stress was also associated with the prevalence of irregular cycles during follow-up (PR =1.33, 95% CI =1.14-1.55). Psychotropic medication use was not appreciably associated with menstrual characteristics after controlling for history of diagnosed depression and/or anxiety. Depressive symptoms, perceived stress, and psychotropic medication use showed little association with menstrual cycle length. CONCLUSION: Higher levels of depressive symptoms and perceived stress were associated with irregular menstrual cycles, but not appreciably associated with menstrual cycle length. Use of psychotropic medications was not meaningfully associated with cycle regularity or length.

Menstrual cycle irregularity and menopause status influence cognition in women with schizophrenia.

Cognitive impairments are a core feature of schizophrenia and contribute significantly to functional complications. Current pharmacological treatments do not ameliorate cognitive dysfunction and the aetiology of cognitive impairments are poorly understood. Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain and have been suggested to also influence cognition. The aim of the current study was to investigate how HPG axis hormones effect cognition, specifically exploring the influence of menopause status and menstrual cycle irregularity on cognitive performance in women with schizophrenia. The data for the present study represents pooled baseline data from three clinical trials. Two hundred and forty female participants with a diagnosis of schizophrenia or schizoaffective disorder were included in the analysis. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status. Hormone assays for serum sex steroids and pituitary hormones (including estradiol, progesterone, luteinising hormone and follicle-stimulating hormone) were conducted and women were classified as postmenopausal; perimenopausal; premenopausal/reproductive, further classified into regular and irregular menstrual cycles. To model a comparison of cognitive performance for i) perimenopausal; ii) post-menopausal women and iii) reproductive aged women with irregular cycles to reproductive aged women with regular cycles a semiparametric regression model (generalised additive mode) was fitted. The results revealed that in females with schizophrenia, menstrual cycle irregularity predicted significantly poorer cognitive performance in the areas of psychomotor speed, verbal fluency and verbal memory. Perimenopause was not associated with cognitive changes and the post-menopausal period was associated with poorer visuospatial performance. This study provides evidence to associate reproductive hormones with cognitive dysfunction in schizophrenia.

Associations of mental health and sleep duration with menstrual cycle irregularity: a population-based study.

This study aimed to examine whether the characteristics of mental health and sleep duration, alone or in combination, are associated with menstrual cycle irregularity. This population-based, cross-sectional study analyzed the data from 4445 women aged 19-49 years, who participated in the Korea National Health and Nutrition Examination Survey 2010-2012. A structured questionnaire was used to assess mental health characteristics, sleep duration, and menstrual cycle irregularity. A multivariable logistic regression analysis was performed. High stress, depressive mood, and suicidal ideation were associated with increased risk of menstrual cycle irregularity after adjusting for confounding variables (odds ratio [95% confidence interval] = 1.33 [1.07-1.65], 1.56 [1.17-2.07], and 1.37 [1.01-1.87], respectively). Short sleep duration (≤ 5 h a day) was significantly associated with higher odds of severe menstrual cycle irregularity with menstrual interval of greater than 3 months (2.67 [1.35-5.27]). Participants with sleep duration of ≤ 5 h a day with psychological stress, depressive mood, or suicidal ideation had higher odds of menstrual cycle irregularity (1.96 [1.26-3.05], 2.86 [1.50-5.44], and 2.25 [1.18-4.29]). This study suggests positive associations of mental health problems and short sleep duration with menstrual cycle irregularity among Korean female adults. Therefore, strategies to deal with psychological stress, depressive mood, and sleep duration are needed for improving the reproductive health of women suffering from menstrual disturbances.

Morphological and molecular variations induce mitochondrial dysfunction as a possible underlying mechanism of athletic amenorrhea.

Female athletes may experience difficulties in achieving pregnancy due to athletic amenorrhea (AA); however, the underlying mechanisms of AA remain unknown. The present study focuses on the mitochondrial alteration and its function in detecting the possible mechanism of AA. An AA rat model was established by excessive swimming. Hematoxylin and eosin staining, and transmission electron microscopic methods were performed to evaluate the morphological changes of the ovary, immunohistochemical examinations and radioimmunoassays were used to detect the reproductive hormones and corresponding receptors. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to test the mtDNA copy number. PCR and western blot analysis were used to test the expression of ND2. The change of morphological features of the rat ovaries revealed evident abnormalities. Particularly, the features of the mitochondria were markedly altered. In addition, reproductive hormones in the serum and tissues of AA rats were also detected to evaluate the function of the ovaries, and the levels of these hormones were significantly decreased. Furthermore, the mitochondrial DNA copy number (mtDNA) and expression of NADH dehydrogenase subunit 2 (ND2) were quantitated by qPCR or western blot analysis. Accordingly, the mtDNA copy number and expression of ND2 expression were markedly reduced in the AA rats. In conclusion, mitochondrial dysfunction in AA may affect the cellular energy supply and, therefore, result in dysfunction of the ovary. Thus, mitochondrial dysfunction may be considered as a possible underlying mechanism for the occurrence of AA.

Association between sleep duration and menstrual cycle irregularity in Korean female adolescents.

OBJECTIVE: The association between sleep and the menstrual cycle in the adolescent population has been scarcely studied. This study aimed to investigate the association between sleep duration and menstrual cycle irregularity among female adolescents using nationwide representative data from the South Korean population. METHODS: This population-based, cross-sectional study used the data collected from Korea National Health and Nutrition Examination Survey 2010-2012, and the data from 801 female adolescents were analyzed. Hierarchical multivariable logistic regression analysis was performed to assess the risk of menstrual cycle irregularity in relation to sleep duration. RESULTS: Subjects with menstrual cycle irregularity accounted for 15% (N = 120). The mean sleep duration in subjects with menstrual cycle irregularity was significantly shorter than that in those without (p = 0.003). Menstrual cycle irregularity prevalence tended to decrease as sleep duration increased (p for trend = 0.004), which was significantly different based on sleep duration and presence of depressive mood (p = 0.011). Sleep duration ≤5 h per day was significantly associated with increased risk of menstrual cycle irregularity compared with that in the subjects whose sleep duration is ≥8 h per day even after adjusting for confounding variables. The odds ratios of menstrual cycle irregularity tended to increase for shorter sleep duration in all adjusted models. CONCLUSION: This study found a significant inverse association between sleep duration and menstrual cycle irregularity among Korean female adolescents. Increasing sleep duration is required to improve the reproductive health of female adolescents.