Pilot Data on the Feasibility And Clinical Outcomes of a Nomegestrol Acetate Oral Contraceptive Pill in Women With Premenstrual Dysphoric Disorder.

Background: Up to 80% of reproductive-aged women experience premenstrual symptoms. Premenstrual Dysphoric Disorder (PMDD) is a severe form, affecting 2-5% of women. Combined oral contraceptive pills (COCPs) are used in the treatment of PMDD. Clinical practice suggests that a newer COCP containing nomegestrol acetate (2.5mg) and 17-beta estradiol (1.5mg), may be a suitable treatment for mood symptoms in PMDD. Materials and Methods: This was a clinical follow-up feasibility study of women who had attended the Monash Alfred Psychiatry research centre, Women's Mental Health Clinic, with a diagnosis of PMDD. 67% of the sample also had concurrent cPTSD, 29% co-morbid anxiety, and 20% depression. They were recommended treatment with nomegestrol acetate/17-beta estradiol. Eligible women were contacted by telephone to answer a questionnaire to assess women's subjective response to nomegestrol acetate/17-beta estradiol, acceptability and the Depression, Anxiety and Stress Scale-21 (DASS-21) after being recommended nomegestrol acetate/17-beta estradiol. The paired-sample t-test was used to determine if there were any statistically significant differences in the DASS-21 scores over the study observation period (before and after taking nomegestrol acetate/17-beta estradiol). Results: 35 (74.5%) women reported a subjective positive mood response to nomegestrol acetate/17-beta estradiol, 31 (63.3%) adhered to the medication, and only 10 (20.4%) women reported side effects as the main reason for discontinuing nomegestrol acetate/17-beta estradiol. There were statistically significant reductions (p<0.05) in the overall DASS-21 scores from before women commenced nomegestrol acetate/17-beta estradiol and after commencement of treatment. Conclusions: This preliminary study supports the acceptability and effectiveness of nomegestrol acetate/17-beta estradiol as a treatment for mood symptoms in PMDD. Further research, particularly a randomized controlled trial, is required to elucidate the effect of nomegestrol acetate/17-beta estradiol treatment on mood in PMDD.

Brain reactivity to emotional stimuli in women with premenstrual dysphoric disorder and related personality characteristics.

AIMS: Premenstrual dysphoric disorder (PMDD) is a psychiatric condition that is associated with the menstrual cycle. Elucidation of the neural regulation mechanisms of brain reactivity to emotional stimuli among women with PMDD may inform PMDD treatment. METHODS: Eighty-six women (42 PMDD, 44 healthy controls) were allocated into two groups (anger-induced group: 23 PMDD vs. 23 controls; depression-induced group: 19 PMDD vs. 21 controls). During the luteal phases of the menstrual cycle, all the women were subjected to functional magnetic resonance imaging (fMRI). fMRI resting-state scans were performed before and after the study participants had performed an emotional stimuli task. After the emotional stimuli task, emotional status of the participants were evaluated by Self-Rating Depression Scales (SDS) and Trait Anger Expression Inventory-II (STAXI-II). In addition, all the participants were requested to complete the Eysenck Personality Questionnaire (EPQ) and the Twenty-Item Toronto Alexithymia Scale (TAS-20). RESULTS: Compared to healthy controls, all women with PMDD exhibited significantly high scores in Tas-20 (p<0.001), higher neuroticism and psychoticism scores as well as significantly low extraversion and social desirability scores (p<0.05). Compared to the controls, f-MRI revealed that PMDD women had elevated ReHo in the middle frontal gyrus (BA10), temporal lobe (BA42), left cerebellum (BA37), as well as decreased activation in the precuneus (BA7), superior frontal gyrus (BA8), lobulus paracentralis (BA6), and right cerebellum (BA48) (p<0.05). Moreover, depression stimuli showed that women with PMDD had elevated ReHo levels in the middle frontal gyrus (BA11), the middle gyrus (BA47) and in the cingulate gyrus (BA23) vs. healthy controls (p<0.05). CONCLUSIONS: Women with more neuroticism and psychoticism, less extraversion and social desirability tend to report PMDD symptoms. Women with this condition experience difficulties in regulating emotions during the luteal phase of the menstrual cycle. Abnormal ReHo levels in the precuneus, superior frontal gyrus, lobulus paracentralis, and right cerebellum may contribute to anger dysregulation. Hypoactivation in the middle frontal gyrus, the middle gyrus and the cingulate gyrus may be generally associated with depression dysregulation in PMDD.

A forced swim-based rat model of premenstrual depression: effects of hormonal changes and drug intervention.

Premenstrual dysphoric disorder (PMDD), a form of premenstrual syndrome (PMS), is a severe health disturbance that affects a patient's emotions; it is caused by periodic psychological symptoms, and its pathogenesis remains unclear. As depression-like symptoms are found in a majority of clinical cases, a reliable animal model of premenstrual depression is indispensable to understand the pathogenesis. Herein, we describe a novel rat model of premenstrual depression, based on the forced swimming test, with a regular estrous cycle. The results showed that in the estrous cycle, the depression-like behavior of rats occurred in the non-receptive phase and disappeared in the receptive phase. Following ovariectomy, the depression-like symptoms disappeared and returned after a hormone priming regimen. Moreover, fluoxetine, an anti-depressant, could reverse the behavioral symptoms in these model rats with normal estrous cycle. Further, the model rats showed significant changes in the serum levels of estrogen and progesterone, hippocampal levels of allopregnanolone, 5-hydroxytryptamine, norepinephrine, and γ-aminobutyric acid (GABA), and in the expression of GABAA receptor 4α subunit, all of which were reversed to physiological levels by fluoxetine. Overall, we established a reliable and standardized rat model of premenstrual depression, which may facilitate the elucidation of PMS/PMDD pathogenesis and development of related therapies.

Hormonal Contraception and Depression: Updated Evidence and Implications in Clinical Practice.

Hormonal contraceptives are used worldwide by more than 100 million women. Some studies have been published about the possible appearance of depressive symptoms when using hormonal contraceptives, but this link is still a matter of debate. The purpose of this review is to provide an update of the literature on this issue, and to investigate the possible explanations of this problem based on animal and human studies. The main pathway responsible for menstrual cycle-related mood changes is the γ-aminobutyric acid pathway, which is sensitive to changes in the levels of progesterone and of its metabolites, the neurosteroids. In particular, allopregnanolone is a potentiating neurosteroid with anxiolytic and anti-convulsant effects whose levels change during a normal menstrual cycle together with progesterone levels. Progestins have different effects on allopregnanolone, mainly owing to their diverse androgenicity. Moreover, they might affect brain structure and function, even though the meaning of these changes has yet to be clarified. It is important to define the groups of women in which negative mood disorders are more likely to occur. Adolescence is a critical period and this age-specific vulnerability is complex and likely bidirectional. Moreover, women with a history of mood affective disorders or premenstrual dysphoric syndrome are at a higher risk when taking contraceptives. In this review, we aim to provide clinicians with advice on how to approach these difficult situations.

Leptin and ghrelin concentrations and eating behaviors during the early and late luteal phase in women with premenstrual dysphoric disorder.

OBJECTIVES: In this study, we evaluated the changes in leptin and ghrelin concentrations, eating behavior, depression, and impulsivity and their correlations within the luteal phase among women with premenstrual dysphoric disorder (PMDD). METHODS: In 63 women with PMDD and 53 healthy controls, we prospectively evaluated serum levels of leptin and ghrelin, Body Mass Index(BMI), and self-reported sweet cravings, cognitive restraint, uncontrolled eating, emotional eating, depression, and impulsivity during the early luteal (EL) and late luteal (LL) phases. RESULTS: Compared with the controls, the women with PMDD had higher BMI, higher leptin concentrations in the EL and LL phase, and leptin concentrations increased from the EL to the LL phase. However, there is no significant difference in ghrelin. Women with PMDD increased sweet cravings and uncontrolled eating from EL to LL phase. No significant correlation was observed between the EL-LL changes in leptin or ghrelin concentrations and those in eating behaviors. Both depression and impulsivity correlated with sweet craving and uncontrolled eating. Depression mediated the association between PMDD and uncontrolled eating. The BMI of women with PMDD positively correlated with their EL-LL change in leptin, and LL depression levels and emotional eating. CONCLUSION: Young women with PMDD had higher leptin concentrations and BMI in the luteal phase. The LL leptin level was not the primary factor responsible for the increased uncontrolled eating of PMDD. Whether the increased eating and depression in the LL phase contribute to the risk of obesity or hyperleptinemia among women with PMDD need to be evaluated in the future.

Neuroimaging premenstrual dysphoric disorder: A systematic and critical review.

Endocrine organizational and activational influences on cognitive and affective circuits are likely critical to the development of premenstrual dysphoric disorder (PMDD), a sex-specific hormone-dependent mood disorder. An overview of the anatomical and functional neural characterization of this disorder is presented here by means of neuroimaging correlates, identified from eighteen publications (n = 361 subjects). While white matter integrity remains uninvestigated, greater cerebellar grey matter volume and metabolism were observed in patients with PMDD, along with altered serotonergic and GABAergic neurotransmission. Differential corticolimbic activation in response to emotional stimuli distinguishes the PMDD brain, namely enhanced amygdalar and diminished fronto-cortical function. Thus far, the emotional distress and dysregulation linked to PMDD seem to be defined by structural, chemical and functional brain signatures; however, their characterization remains sparsely studied and somewhat inconsistent. Clear and well-replicated neurobiological features of PMDD are needed to promote timely diagnoses and inform development of prevention and treatment strategies.

Are there temporal subtypes of premenstrual dysphoric disorder?: using group-based trajectory modeling to identify individual differences in symptom change.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnosis characterized by the cyclical emergence of emotional and physical symptoms in the luteal phase of the menstrual cycle, with symptom remission in the follicular phase. Converging evidence highlights the possibility of distinct subtypes of PMDD with unique pathophysiologies, but temporal subgroups have yet to be explored in a systematic way. METHODS: In the current work, we use group-based trajectory modeling to identify unique trajectory subgroups of core emotional and total PMDD symptoms across the perimenstrual frame (days -14 to +9, where day 0 is menstrual onset) in a sample of 74 individuals prospectively diagnosed with DSM-5 PMDD. RESULTS: For the total daily symptom score, the best-fitting model was comprised of three groups: a group demonstrating moderate symptoms only in the premenstrual week (65%), a group demonstrating severe symptoms across the full 2 weeks of the luteal phase (17.5%), and a group demonstrating severe symptoms in the premenstrual week that were slow to resolve in the follicular phase (17.5%). CONCLUSIONS: These trajectory groups are discussed in the context of the latest work on the pathophysiology of PMDD. Experimental work is needed to test for the presence of possible pathophysiologic differences in trajectory groups, and whether unique treatment approaches are needed.

Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back.

Premenstrual dysphoric disorder (PMDD) affects over 5% of women, with symptoms similar to anxiety and major depression, and is associated with differential sensitivity to circulating ovarian hormones. Little is known about the genetic and epigenetic factors that increase the risk to develop PMDD. We report that 17ß-estradiol (E2) affects the behavior and the epigenome in a mouse model carrying a single-nucleotide polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met), in a way that recapitulates the hallmarks of PMDD. Ovariectomized mice heterozygous for the BDNF Met allele (Het-Met) and their matched wild-type (WT) mice were administered estradiol or vehicle in drinking water for 6 weeks. Using the open field and the splash test, we show that E2 add-back induces anxiety-like and depression-like behavior in Het-Met mice, but not in WT mice. RNA-seq of the ventral hippocampus (vHpc) highlights that E2-dependent gene expression is markedly different between WT mice and Het-Met mice. Through a comparative whole-genome RNA-seq analysis between mouse vHpc and lymphoblastoid cell line cultures from control women and women with PMDD, we discovered common epigenetic biomarkers that transcend species and cell types. Those genes include epigenetic modifiers of the ESC/E(Z) complex, an effector of response to ovarian steroids. Although the BDNF Met genotype intersects the behavioral and transcriptional traits of women with PMDD, we suggest that these similarities speak to the epigenetic factors by which ovarian steroids produce negative behavioral effects.

Resting-state functional connectivity in women with PMDD.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls. METHODS: Thirty-six women (18 PMDD, 18 control) participated in fMRI during the follicular and luteal phases of the menstrual cycle. At each time, resting-state functional connectivity was evaluated both before and after participants performed an emotion regulation task. The ECN was identified using independent components analysis, and connectivity of left and right amygdala seeds was also evaluated. RESULTS: Nonparametric permutation testing identified a cluster in the left middle temporal gyrus (MTG) with significantly stronger connectivity to the left ECN in women with PMDD vs. controls in all four fMRI sessions. Women with PMDD exhibited no difference in functional connectivity between menstrual cycle phases. Amygdala connectivity did not differ between the groups but differed significantly with menstrual phase, with left amygdala connectivity to cingulate cortex being significantly stronger during the follicular vs. luteal phase. Right amygdala connectivity to the middle frontal gyrus was also stronger during the follicular vs. luteal phase, with no group differences. These findings suggest that women with PMDD have different intrinsic network dynamics in the left executive control network compared to healthy controls.

Increased sensitivity to social exclusion during the luteal phase: Progesterone as resilience factor buffering against ostracism?

A woman's social behaviour reportedly varies across the menstrual cycle. In this study, we estimated changes in sensitivity to social exclusion across the menstrual cycle and scrutinized the related role of progesterone. Forty-nine naturally cycling women played a virtual ball-tossing game (Cyberball) to manipulate social inclusion. All participants underwent inclusion and exclusion conditions during the late follicular and the luteal phase. We assessed salivary progesterone concentrations at each cycle phase. After each Cyberball session we measured positive/negative mood using the Multidimensional Mood State Questionnaire (MDMQ). Multilevel analyses indicated that women showed worse mood following exclusion as compared to inclusion conditions (p = 0.014). Notably, this exclusion effect was more pronounced during the luteal phase than the late follicular phase (p = 0.029). As expected, progesterone concentrations were higher during the luteal phase as compared to the late follicular phase, but interestingly, progesterone concentrations were negatively associated with exclusion effects. When accounting for mediation via progesterone, direct cycle-phase related differences in social exclusion effects even increased as compared to the model without mediator. These findings suggest that progesterone may function as buffer against negative feelings that result from being socially excluded. The relevance of these findings for Premenstrual Dysphoric Disorder (PMDD) are discussed, and we conclude that social exclusion may represent an important research domain criterion (RDoC) of relevance for PMDD, with progesterone pointing to new potential pharmacological targets.

Menstrual Cycle Disorders in Professional Female Rhythmic Gymnasts.

The aim of this research was to compare menstrual cycles, menstrual disorders, and the prevalence of premenstrual syndrome (PMS)and premenstrual dysphoric disorder (PMDD) in professional female gymnasts and their peers who donot practice any sport, and to identify factors causing a predisposition to premenstrual tension syndrome and premenstrual dysphoric disorders in both groups. The prospective study involved apopulation of 85 girls. The study group consisted of 45 professional female gymnasts (15-17 years of age) who lived inthe territory of Silesia, in the southern area of Poland. The control group consisted of 40 girls of the same age who lived in the same area but did not professionally practice any sport. The research tools included a questionnaire, a daily diary of PMS symptoms, a daily diary of PMDD symptoms, and a premenstrual symptom screening tool (PSST). The study showed that intensive physical activity undertaken by girls before their first menstruation is a menarche-delaying factor andthat competitive sport promotes premenstrual syndrome and premenstrual dysphoric disorder. The risk factors for PMS and PMDD were also identified, andincluded alcohol and coffee consumption.

Psychological factors and premenstrual syndrome: A Spanish case-control study.

OBJECTIVE: To assess whether the psychological variables perceived stress, neuroticism and coping strategies, are associated with Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Syndrome (PMDD). DESIGN: Case-control study with incident cases using the Spanish public healthcare system. SETTING: 3 major public hospitals and one family counseling and planning center. POPULATION: Women consulting for troubles related to menstruation and for other motives such as screening for uterine cancer, contraception counselling or desire for pregnancy. METHODS: Logistic regression. MAIN OUTCOME MEASURES: Odds of PMS and PMDD. RESULTS: 285 PMS and 285 age-matched controls, as well as 88 PMDD cases and 176 controls participated in the study. Medium and high levels of perceived stress were associated with an increase in the odds of PMS (Odds Ratio (OR) = 2.49; 95%CI: 1.41-4.39 and OR = 4.90; 95%CI: 2.70-8.89, respectively). For PMDD the results were: OR = 2.61; 95%CI: 1.35-5.05 and OR = 5.79; 95%CI: 2.63-12.76, respectively. Subjects with medium and high levels of neuroticism were also at higher odds of suffering from PMS (OR = 2.53; 95%CI: 1.06-6.06 and OR = 8.05; 95%CI: 3.07-2.12, respectively). For PMDD, the results were OR = 3.70; 95%CI: 1.27-10.77 and 5.73: 95%CI: 1.96-16.77, respectively. High levels in the large majority of coping strategies were also associated with increased odds of PMS and PMDD. CONCLUSIONS: Psychological factors including perceived stress, neuroticism and coping strategies are strongly related to PMS/PMDD. This association is unlikely to be due to confounding or misclassification bias. A reverse causation process cannot be ruled out although its likelihood is remote.

The impact of menstrual symptoms on everyday life: a survey among 42,879 women.

BACKGROUND: Menstrual symptoms such as dysmenorrhea, heavy menstrual bleeding, and perimenstrual mood disorders are known to be widespread among the general population. From studies in patients with endometriosis and premenstrual disorder, it has been shown that these symptoms can have a large impact on women's quality of life and account for substantial health care use. Furthermore, it is estimated that many women initially do not consult a doctor while facing menstrual symptoms. Consequently, the impact of menstrual symptoms on daily activities in the general population is unknown. OBJECTIVE: To obtain a nationwide overview of menstrual symptoms and their impact on everyday activities. STUDY DESIGN: Nationwide, cross-sectional, internet-based survey among 42,879 women aged 15-45 years, conducted from July to October 2017. OUTCOME MEASURES: presence of menstrual symptoms, pain or intensity score, impact on daily activities. RESULTS: Dysmenorrhea was the most common symptom, with a prevalence of 85%, followed by psychological complaints (77%), and tiredness (71%). During their menstrual period, 38% of all women reported not to be able to perform all their regular daily activities. From the women that had to skip tasks because of their symptoms, only 48.6% told their family that menstrual symptoms were the reason for the transfer of tasks. CONCLUSION: Menstrual symptoms are widespread among the general population. One in 3 women quit daily activities owing to menstrual symptoms. Half of all women did not mention menstrual complaints being the reason for transferring tasks in a family setting. These results must be interpreted with caution owing to the potential for selection bias. However, considering the impact of menstrual symptoms on daily activities in a large group of women, it is time to open the societal dialogue and improve education for both patients and doctors.

Changing the perception of premenstrual dysphoric disorder - An online-experiment using the Stereotype Content Model.

Women with Premenstrual Dysphoric Disorder (PMDD) are often faced with prejudices about the premenstrual phase. The aim of this study was to investigate whether providing information (psychoeducation) could improve study participants' perception of a PMDD-patient and whether experimentally-induced prejudices about PMDD resulted in stigmatization. Two hundred sixteen students (50% female; aged 18-42 years) from Philipps University Marburg participated in January 2014. Participants were randomly assigned to one of two experimental groups (EG1, EG2) or to a control group (CG). EG1 read a text informing about PMDD. EG2 read a text with stereotypic PMDD-information. CG received a text with information unrelated to PMDD. Then, all participants watched a video of a woman reporting about her PMDD. Finally, participants appraised the woman on the cognitive dimensions warmth and competence as well as on PMDD-related attributes (depressive symptoms, emotional regulation). Participants of EG1 rated the woman as warmer (p <  .001), more competent (p =  .006), and with less depressive symptoms (p < .001) than the CG. The results by study group did not differ by gender. Stereotypic information did not differ significantly among the study groups. Psychoeducation can facilitate the understanding of PMDD-patients and should be integrated in future research on PMDD-treatments.

Sex differences during emotion processing are dependent on the menstrual cycle phase.

Sex differences in the neural processing of emotion are of special interest considering that mood and anxiety disorders predominant in females. However, these sex-related differences were typically studied without considering the hormonal status of female subjects, although emotion processing in the brain was shown to differ between phases of the menstrual cycle. In this functional MRI study, we demonstrated the influence of the menstrual cycle phase on sex differences in brain activity and functional connectivity during negative and positive emotions, using two different paradigms: emotion perception and emotion experience. Twenty naturally cycling healthy women without premenstrual symptoms were scanned twice: during the mid-follicular and late-luteal menstrual phases, and compared to a matched group of twenty healthy men. During negative emotion perception, men showed increased neural activity in the right hippocampal formation relative to women in the mid-follicular phase, and increased activity in the right cerebellum relative to women in the late-luteal phase. During experience of amusement, reduced putamen-ventrolateral prefrontal cortex and putamen-dorsomedial prefrontal cortex functional connectivity were observed for women in the late-luteal phase relative to men and associated with levels of sex hormones. These neural and hormonal findings were complemented by behavioral reports of reduced amusement and increased sadness in late-luteal women. Our results demonstrate menstrual phase-dependent sex differences in emotion perception and experience and may suggest a biological tendency for a deficient experience of pleasure and reward during the late-luteal phase. These findings may further shed light on the underlying pathophysiology of premenstrual dysphoric disorder.

Negative cognitive styles as risk factors for the occurrence of PMS and PMDD.

Background: The purpose of our study is to verify whether elements of cognitive vulnerability to affective disorders may enhance the occurrence of PMS/PMDD. Methods: In total, 293 women with regular cycles took part in the study. The subjects were exposed to failure during the follicular phase or luteal phase, as appropriate, and the attributional style of failure, cognitive triad inventory (CTI) and presence of biased information processing were determined. The mood of the subjects before and after failure was measured, and the depressive mood was screened by CES-D. The occurrence of PMS/PMDD was assessed on the basis of PSST. Results: The women suffering from PMS/PMDD differed from those without PMS in terms of the cognitive triad, the use of positive and negative adjectives when describing themselves and biased information processing. In the luteal cycle phase, considerably greater sadness and irritation were observed in women with PMS/PMDD after experiencing failure, but only in those from the group not taking oral contraceptives. Conclusions: Negative cognitive styles are an important factor in the development of PMS/PMDD. PMDD is similar to major depression regarding cognitive vulnerability. Only in the case of PMDD was biased information processing in the luteal cycle phase recorded.

No Menstrual Cyclicity in Mood and Interpersonal Behaviour in Nine Women with Self-Reported Premenstrual Syndrome.

BACKGROUND/AIMS: Before diagnosing premenstrual dysphoric disorder (PMDD), 2 months of prospective assessment are required to confirm menstrual cyclicity in symptoms. For a diagnosis of premenstrual syndrome (PMS), this is not required. Women with PMDD and PMS often report that their symptoms interfere with mood and social functioning, and are said to show cyclical changes in interpersonal behaviour, but this has not been examined using a prospective approach. We sampled cyclicity in mood and interpersonal behaviour for 2 months in women with self- reported PMS. METHODS: Participants met the criteria for PMS on the Premenstrual Symptoms Screening Tool (PSST), a retrospective questionnaire. For 2 menstrual cycles, after each social interaction, they used the online software TEMPEST to record on their smartphones how they felt and behaved. We examined within-person variability in negative affect, positive affect, quarrelsomeness, and agreeableness. RESULTS: Participants evaluated TEMPEST as positive. However, we found no evidence for menstrual cyclicity in mood and interpersonal behaviour in any of the individual women (n = 9). CONCLUSION: Retrospective questionnaires such as the PSST may lead to oversampling of PMS. The diagnosis of PMS, like that of PMDD, might require 2 months of prospective assessment.

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

From a psychological perspective, the menstrual cycle has been a research topic for more than 50 years. The most recent menstrual cycle research has been driven by an increased interest in sex differences in neuroscience, and the urge to understand sex disparities in prevalence, clinical presentation, and treatment response in psychiatric or neurologic disorders. Indeed, the menstrual cycle is an excellent model of ovarian steroid influence on emotion, behavior, and cognition. This review summarizes the emotion-related and cognitive findings of methodologically sound menstrual cycle studies. In particular, the review is devoted to the sex hormone-induced emotional disturbances in women with premenstrual dysphoric disorder, a subgroup of women responding with enhanced sensitivity to the normal fluctuations in endogenous hormone levels during the menstrual cycle. In addition, emotion processing and cognitive findings across the menstrual cycle in healthy women are also discussed. The overall conclusion is that that menstrual cycle differences in sexually dimorphic cognitive tasks are small and difficult to replicate. Emotion-related changes are more consistently found and are better associated with progesterone and the luteal phase, than with estradiol.

Premenstrual appetite and emotional responses to foods among women with premenstrual dysphoric disorder.

The aim of the study was to evaluate changes in late-luteal appetite for highly sweet (HS) and highly salty and fatty (HSF) foods in women with premenstrual dysphoric disorder (PMDD). After initial assessment in a psychiatric interview, the premenstrual symptoms screening tool (PSST) was used to identify women with moderate-to-severe premenstrual symptoms. Sixty-seven women with PMDD and 74 healthy controls were evaluated in the early-follicular and late-luteal (pre-menstrual) phases of the menstrual cycle. Because the PSST is designed to assess symptoms only in the late-luteal phase, an 11-point Likert scale was used to rate PMDD symptoms once a week in the evaluation mentioned previously and the following two menstrual cycles. Participants were shown pictures of 15 highly sweet (HS) and 15 highly salty and fatty (HSF) foods, desire to eat each food was rated on an eleven-point Likert scale (0, "none at all"; 10, "extreme desire"), and sweet-food craving was rated using the food craving-state questionnaire. Emotional responses to the foods were measured with a four-point Likert scale we previously validated. Depression, irritability, and impulsivity were measured with standard psychiatric instruments. Women with PMDD, but not control women, had late-luteal phase elevations in desire to eat HS food, sweet-food craving and emotional responses to HS foods. Desire to eat for HSF foods did not differ significantly across the menstrual cycle between groups. There were significant correlations between emotional responses to and desire to eat HS foods. Moreover, late-luteal phase irritability and impulsivity scores were associated with desire to eat HS foods. These data suggest that targeted assessment of increased late-luteal appetites for HS foods may facilitate clinical interventions in women with PMDD.