How to study the menstrual cycle as a continuous variable: Implementing phase-aligned cycle time scaling (PACTS) with the menstrualcycleR package.

Prevention of menstrual migraine with perimenstrual transdermal 17-β-estradiol: a randomized, placebo-controlled, double-blind crossover study

Background: Premenstrual dysphoric disorder (PMDD) is characterized by psychological and physiological function impairment and can pose threat on adolescents’ academic performance and well-being. Objectives: This study aimed to determine the prevalence and determinants of PMDD among secondary school female students at Al-Iskan sector, Makkah Al-Mukarramah. Methods: A cross-sectional study involving 246 secondary school female students in Makkah Al-Mukarramah. A self-administered questionnaire was used for data collection. Variables such as demographic characteristics and PMDD were determined. Results: A total of 246 respondents participated in the study. Their age ranged from 16 to 21 years with an average of 17.0±0.9, Saudi national (82.1%), single (98.8%), and have no children (99.6%). In terms of educational attainment, about 37.4% of the respondents are in primary level, followed by 35.4% in the tertiary level, and 27.2% in the secondary level. In terms of individual symptoms experienced by the respondents before menstrual cycle, more than 4 in every 5 participants have suffered from mood swings or nervousness (82.5%) and from lethargy (80.1%). In addition, more than half of females interviewed have suffered too much or too little sleep (74.8%), a change in appetite increase or decrease (69.9%), muscle and joint pain (67.1%), difficulty in concentration and lack of effectiveness and productivity at work (65.0%), low indifference to the usual activities (58.9%), depression (58.5%), headaches (54.5%), from a sense of bloating in the abdomen (52.4%), and aggression (51.2%). Based on the findings of this study, about 40.7% of the participants were found to experienced irregular menstrual cycles. Age was found to be statistically significant associated with regularity of menstrual cycles. In terms of educational level, chi-square test revealed significant statistical association between educational level and premenstrual dysphoric disorder symptoms, such as lethargy, too much or too little sleep, and breast pain or swelling. Lastly, significant association was found between menstrual cycle and change in appetite. Conclusions: PMDD is characterized by substantial weakening of the ability to function socially or occupationally for a week prior to menstruation. It can be expressed through a combination of emotional, physical, and lifestyle symptoms. As such, management and treatment of PMDD must be made in accordance to the severity, types of symptoms, patient’s age, and preferences.

Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder

We investigated whether women diagnosed with comorbid bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) experience higher disruptions in biological rhythms in two independent study samples. The first study has a population-based sample of 727 women, including 104 women with PMDD only, 43 women with BD only, 24 women with comorbid PMDD and BD, and 556 women without BD or PMDD (controls). Biological rhythm disruptions were cross-sectionally evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). The second study enrolled 77 outpatient women who completed prospective assessments at two timepoints: during the mid-follicular and the late-luteal phases of their menstrual cycles, using the BRIAN, and included 19 women with PMDD, 16 with BD, 17 with comorbid PMDD and BD, and 25 controls. In the population-based sample, all the diagnostic groups (BD, PMDD, BDPMDD) presented greater biological rhythm disruption than controls. In addition, women with BD presented greater overall biological rhythms disruption, and greater disruption in sleep, activity, and eating patterns, than women with PMDD. In the outpatient sample study, women with BDPMDD showed greater disruption in the social domain than women with PMDD. In the outpatient sample, women with BDPMDD reported significantly higher disruptions in biological rhythms across both the follicular and the luteal phases of the menstrual cycle. The comorbidity between BD and PMDD may affect biological rhythms beyond the luteal phase of the menstrual cycle. These results support previous literature on the increased illness burden of women diagnosed with comorbidBD and PMDD.

Background: Migraine is a common health condition in both men and women. Premenstrual syndrome (PMS) affects many women during their menstrual cycle, with around 50–60% of women with migraine attacks experiencing menstrual headaches. Most have mild symptoms, but 5–8% suffer from moderate to severe symptoms, causing distress and functional issues. Pure menstrual migraine (PMM) occurs in about 50% of women with migraine, and it can be debilitating in terms of frequency and severity. This information is crucial for Saudi Arabian medical professionals to provide better care and support, improving the quality of life for women with PMS and menstrual migraine (MM) attacks. Objectives: To estimate the prevalence of MM in women, to evaluate the severity and frequency of MM in women with PMS, and to identify potential risk factors aggravating MM in women with PMS in Saudi Arabia. Methodology: A cross-sectional community-based study was conducted on reproductive-aged (18–50 years) women who had regular menstrual cycles and were diagnosed with PMS, using a self-administered questionnaire between December 2022 to May 2023 in Saudi Arabia. Results: Out of the 2130 female participants, 397 (18.6%) had migraine. Among these 397 migraine sufferers, 230 (57.9%) experienced MM, while 167 (42.1%) had non-MM. In reproductive women in general, MM occurred in 10.7% of cases, while non-MM was observed in 7.8%. There is a correlation between increasing BMI and an increased incidence of MM. About one-third of the participants experienced moderate disability due to migraine attacks, with 134 (33.8%) individuals affected. Additionally, most MM sufferers missed at least 3 days of work in the last 3 months due to their condition. Conclusions: Migraine attacks occurring during the menstrual cycle impair the ability to engage in social, physical, household, and academic activities, often hindering the fulfillment of professional commitments. To gain a deeper understanding of menstrual and non-menstrual migraine attacks, it is essential to conduct extensive prospective studies aimed at developing effective management strategies.

Introduction Most women with premenstrual dysphoric disorder (PMDD) report sleep disturbances. Our group found normal polysomnographic (PSG) sleep efficiency and increased slow wave sleep (SWS) across the menstrual cycle in women with PMDD and insomnia compared to controls. Reduced melatonin levels were found in PMDD women compared to controls, with reduced secretion during their luteal phase (LP) compared to follicular phase (FP). Here, we investigated the effects of exogenous melatonin in the patients we previously studied. Methods Five patients (age, mean: 33.6, SD: 2.7) diagnosed prospectively with PMDD and insomnia participated in the study. Following a baseline assessment, patients took 2 mg of slow-release melatonin 1h before bedtime during their LP for three consecutive menstrual cycles. At baseline (treatment-free condition), patients spent every third night of their menstrual cycle sleeping in the laboratory. Measures included morning urinary 6-sulfatoxymelatonin (aMt6), PSG sleep, nocturnal core body temperature (CBT), visual analogue scale for mood (VAS-Mood), Prospective Record of the Impact and Severity of Menstrual symptoms (PRISM), subjective sleep and ovarian hormones (estrogen and progesterone). Participants also underwent two 24-hour intensive physiological monitoring (during the FP and LP) in time-isolation/constant conditions to determine 24-hour plasma melatonin and CBT rhythms. The same measures were repeated during their third menstrual cycle of melatonin administration. Results In the intervention condition compared to baseline, we found increased urinary aMt6 (p<0.001), reduced objective SOL (p=0.01), SWS (p<0.001) and increased Stage 2 sleep (p<0.001). Increased urinary aMt6 was associated with reduced SWS (r=-0.51, p<0.001). Circadian parameters derived from 24-hour plasma melatonin and CBT did not differ between conditions, except for an increased melatonin mesor in the intervention condition (p=0.01). Ovarian hormones were comparable between the conditions (p≥0.28). Symptoms improved in the intervention condition, as measured by the VAS-Mood (p=0.02) and the PRISM (p<0.001). Conclusion We have shown normalization of SWS and reduction in self-reported mood and somatic symptoms after administrating exogenous melatonin in women with PMDD. These findings support a role for disturbed melatoninergic system in PMDD that can be partially corrected by exogenous melatonin. Support (if any) This study was supported by the Canadian Institutes of Health Research (CIHR)

Women with premenstrual dysphoric disorder (PMDD) experience mood symptoms related to the increase in progesterone and the neuroactive steroid allopregnanolone. Our hypothesis is that allopregnanolone is the symptom provoking factor. The rationale for the present study was to treat PMDD patients with the GABAA receptor modulating steroid antagonist, sepranolone (isoallopregnanolone). Patients (n = 206) with PMDD from 12 European centers were randomized in a parallel double-blind study and treated with placebo, sepranolone 10 mg and 16 mg. Patients administered sepranolone subcutaneously every 48 h during the 14 premenstrual days of three consecutive menstrual cycles. After obtaining informed consent, the PMDD diagnosis was confirmed according to DSM-5 and verified with two menstrual cycles of daily symptom ratings using the Daily Record of Severity of Problems (DRSP) scale in an eDiary. Inclusion and exclusion criteria stipulated that the women should be essentially healthy, not pregnant, have no ongoing psychiatric disorder or take interfering medications, and have regular menstrual cycles. The study’s primary endpoint was the Total symptom score (Sum21, the score for all 21 symptom questions in the DRSP). In the prespecified statistical analysis the average score of the 5 worst premenstrual days in treatment cycles 2 and 3 were subtracted from the corresponding average score in the two diagnostic cycles. The treatment effects were tested using analysis of variance in a hierarchal order starting with the combined active sepranolone treatments vs. placebo. The prespecified analysis of Sum21 showed a large treatment effect of all three treatments but no statistically significant difference to placebo. However, the ratings of distress showed a significant treatment effect of sepranolone compared to placebo (p = 0.037) and the ratings of impairment showed a trend to greater treatment effect of sepranolone compared to placebo. Many women with PMDD had symptoms during a longer period than the late luteal phase. It has previously been shown that 9 premenstrual days may be more representative for comparison of PMDD symptom periods than the 5 worst premenstrual days. A post hoc analysis was undertaken in the per protocol population investigating the treatment effect during 9 premenstrual days in the third treatment cycle. The Sum21 results of this analysis showed that the sepranolone 10 mg was significantly better than placebo (p = 0.008). Similar significant treatment effects were found for the impairment and distress scores. A significantly larger number of individuals experienced no or minimal symptoms (Sum21 <42 points) with the 10 mg sepranolone treatment compared to placebo (p = 0.020). The results indicate that there is an attenuating effect by sepranolone on symptoms, impairment, and distress in women with PMDD especially by the 10 mg dosage. Sepranolone was well tolerated, and no safety concerns were identified.

Commentary on “Menstrually Related Disorders: Points of Consensus, Debate, and Disagreement”

Premenstrual dysphoric disorder is a depressive disorder affecting 5%-8% of people with menstrual cycles. Despite evidence that facial emotion detection is altered in depressive disorders, with enhanced detection of negative emotions (negativity bias), minimal research exists on premenstrual dysphoric disorder. The goal of this study was to investigate the effect of premenstrual dysphoric disorder symptoms and the premenstrual phase on accuracy and intensity at detection of facial emotions. Cross-sectional quasi-experimental design. The Facial Emotion Detection Task was administered to 72 individuals assigned female at birth with no premenstrual dysphoric disorder (n = 30), and provisional PMDD (n = 42), based on a retrospective Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition-based measure of premenstrual dysphoric disorder. Facial emotion detection was examined both irrespective of menstrual cycle phase, and as a function of premenstrual phase (yes, no). The task used neutral-to-emotional facial expression morphs (15 images/morph). Participants indicated the emotion detected for each image within the progressive intensity morph. For all six basic emotions (sad, angry, fearful, happy, disgust, and surprise), two scores were calculated: accuracy of responses and the intensity within the morph at which the correct emotion was first detected (image number). Individuals reporting moderate/severe symptoms of premenstrual dysphoric disorder had more accurate and earlier detection of disgust, regardless of cycle phase. In addition, those with provisional premenstrual dysphoric disorder detected sad emotions earlier. A premenstrual dysphoric disorder group × cycle phase interaction also emerged: individuals reporting premenstrual dysphoric disorder symptoms were more accurate at detecting facial emotions during the premenstrual phase compared to the rest of the cycle, with a large effect size for sad emotions. The findings suggest enhanced facial emotion processing in individuals reporting symptoms of premenstrual dysphoric disorder, particularly for sadness and disgust. However, replication is required with larger samples and prospective designs. This premenstrual dysphoric disorder premenstrual emotion detection advantage suggests an adaptive cognitive mechanism in premenstrual syndrome/premenstrual dysphoric disorder, and challenges stigma surrounding premenstrual experiences.

Eighty-nine women seeking a diagnostic evaluation for premenstrual syndrome provided daily symptom ratings for two or more menstrual cycles. Three scoring methods were used for assessing symptom change associated with the late luteal phase of the menstrual cycle. Diagnoses of late luteal phase dysphoric disorder (LLPDD) were considered using the DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) criteria. Lifetime mental history data were collected using the Schedule for Affective Disorders and Schizophrenia-Lifetime (SADS-L). We sought to determine whether women seeking evaluation for premenstrual complaints, but who did not meet the criteria for LLPDD, in fact displayed a higher incidence of psychiatric disorders or symptomatology. Depending on the criteria for scoring symptom severity, 13–28% of the women met criteria for LLPDD. A present or past episode of a psychiatric disorder was present in 45% of the women. Psychiatric diagnosis was not significantly associated with the pre...

It is presently not known whether endogenous neuroactive steroid hormone trajectories across the menstrual cycle are distinguishable in women with premenstrual dysphoric disorder (PMDD). To improve the rigor in this area of research, we implemented a validated study methodology, involving blood sample collection at 8 key menstrual cycle timepoints, following which the study data is realigned so that all women are compared at the same biological window (i.e., menstrual cycle subphase). Using liquid chromatography-mass spectrometry (LC-MS), we analyzed serum levels of nine steroid hormones previously implicated in the etiology of PMDD, including allopregnanolone. Other than progesterone (p ≤ 0.001), none of the steroid hormones displayed significant changes across menstrual cycle subphases when comparing participants with PMDD to the healthy controls. A thorough investigation of the progesterone trajectory showed that its left shift in the luteal phase (e.g., earlier rise in progesterone) exposes women with PMDD to a higher periovulatory progesterone and a more acute withdrawal in the late luteal subphase. Results of the present study indicate that the largely overlooked brief periovulatory subphase should be thoroughly examined in PMDD and agree with prior conclusions that rapid progesterone withdrawal associates with the development of negative affect.

Objectives: Premenstrual dysphoric disorder is a somatopsychic condition that develops about a week before the start of menstruation and is brought on by fluctuating sex steroid levels that follow an ovulatory menstrual cycle. Therefore, this study aimed to assess the magnitude of premenstrual dysphoric disorder and associated factors among Haramaya University graduating class female students, in eastern Ethiopia. Methods: An institutional-based cross-sectional study was conducted from 1 to 30 November 2022 among Haramaya University graduating class female students using a simple random sampling technique. The data were cleaned, coded, and entered into the Epi-data 3.01 before being exported and analyzed with Statistical Package of Social Science 20 versions. The premenstrual dysphoric disorder was assessed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision. To identify associated factors a bivariable logistic regression analysis was conducted to determine the association between each independent variable and the outcome variable. The multivariable logistic regression model includes all variables with a p-value of less than 0.25 in the bivariate logistic regression analysis. The adjusted odds ratio with a 95% confidence interval was computed when the p-value was less than 0.05, which was considered statistically significant. Results: Out of 282 samples, 274 study participants were involved providing a response rate of 97.2%. The prevalence of premenstrual dysphoric disorders was 64.6% (95% CI: 59.5–70.4). Participants with the irregular menstrual cycle (AOR = 2.24; 95% CI: 1.26–4.34), heavy menstrual flow (AOR = 2.53; 95% CI: 1.84–7.59), moderate menstrual flow (AOR = 2.29; 95% CI: 1.02–5.26), severe menstrual pain (AOR = 5.69; 95% CI: 1.86–7.42) and those who have depressive symptoms (AOR = 2.46, 95% CI: 1.08–5.68) were variables associated with premenstrual dysphoric disorders. Conclusion: The prevalence of premenstrual dysphoric disorder was relatively high. Severe menstrual pain, menstrual irregularity, heavy menstrual flow, and a history of depression had significant associations with premenstrual dysphoric disorder. It will be better if higher institution administrators design and implement methods to screen and intervene premenstrual dysphoric disorder among female students.

Premenstrual Dysphoric Disorder (PMDD) can be differentiated from Premenstrual Syndrome (PMS) by the use of the research criteria provided by the Diagnostic and Statistical Manual (DSM) IV. Indeed, PMS corresponds to mild clinical symptoms, such as breast tenderness, bloating, headache and concomitant minor mood changes, while premenstrual magnification occurs when physical and psychological symptoms of a concurrent axis I disorder get worse during the late luteal phase. Changes in appetite and eating behavior have been documented in women suffering from PMS, with an increased food intake occurring during the luteal phase. Moreover, in women with PMS, a major effect of the phase of the menstrual cycle on appetite has been documented and a high correlation with self-ratings of mood, particularly depression, has been described only in such disturbance. The aim of the present study was to analyse the clinical similarities between PMDD and Eating Disorders (in particular Bulimia Nervosa and Binge Eating Disorder). Thus, we compared the DSM III-R comorbidity, the personality dimensions and the eating attitudes in these patients, attempting to identify any relationship between groups. Twelve PMDD women (mean age 28 years), diagnosed using DSM IV criteria and premenstrual assessor form, were compared with 10 eating disorder (ED) women (6 Bulimia Nervosa, 4 Binge Eating Disorder) (mean age 25 years) and with 10 control women matched for age. The following instruments were used: (i) clinical interview with DSM III-R criteria (SCID); (ii) a psychometric study with TPQ for the evaluation of three personality dimensions (novelty seeking, harm avoidance and reward dependence); (iii) EAT/26 for the evaluation of eating attitudes. Results show that a high comorbidity for mood and anxiety disorders in PMDD and ED is well documented. Our PMDD patients share a 16.6% of comorbidity with ED, whereas such an association is present only in 2.3% of the general population. In addition, as a common clue, the personality dimension, harm avoidance, linked to a serotonin mediation is significantly more frequent in PMDD and ED than in normal controls. from the present study it seems clear that a certain degree of similarity exists between the PMDD and ED. However, whether or not these two disorders really share common ground from a physiopathological point of view still has to be clarified by more extensive studies.

The Menstrual Cycle Influences Emotion but Has Limited Effect on Cognitive Function.

Prevalence and predictors of premenstrual dysphoric disorder (PMDD) in older premenopausal women: The Harvard Study of Moods and Cycles