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1.  Work Stress, Premenstrual Syndrome and Dysphoric Disorder: Are There Any Associations? 
Women with recurrent and severe symptoms are diagnosed as having premenstrual syndrome (PMS), and if they suffer from severe affective symptoms, a diagnosis of premenstrual dysphoric disorder (PMDD) is made. The purpose of this study was to determine the association of work stress with PMS and PMDD.
Fifty-five female medical students in their internship program (ten 24-hour shifts per month) and 38 third-year female medical students without any shift duties were asked to participate in this study. A questionnaire was used to record demographic information and a self-report inventory was used to measure 13 symptoms relevant to PMS and PMDD according to DSM-IV criteria. All participants were asked to complete the inventory every night around midnight for those on shifts or before going to bed at home for 60 consecutive nights.
Out of 55 volunteers in the shift-work group, 31 (56%) fulfilled the diagnostic criteria for PMS in contrast to 12 (32%) in the control group. The frequency of PMDD was 12 (22%) in the intern group and 5 (13%) in the control group. Twenty one students (55%) from the control group did not have PMS or PMDD, compared to 12 (22%) students from the shift workers. Decreased energy (70.9%) and irritability (65.4%) were the most frequent symptoms during the luteal phase in the shift-work group.
Work stress and an increase in responsibility may produce or exacerbate PMS. Self-help approaches to induce self-awareness, along with psychological and psychiatric interventions, may help susceptible women to overcome this cyclic condition in order to increase their productivity as well as their quality of life.
PMCID: PMC3371938  PMID: 22737463
Premenstrual syndrome; Premenstrual dysphoric disorder; Work stress; Female; Medical students
2.  Premenstrual Disorders: Prevalence and Associated Factors in a Sample of Iranian Adolescents 
Premenstrual disorders usually refer to Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD). This study was designed to find out the frequency of premenstrual disorders and evaluate the associated factors in a sample of Iranian adolescents.
This study was conducted to investigate the frequency of premenstrual disorders (PMS and PMDD) based on Premenstrual Assessment Scale (PAS) and also to determine the association of some demographic and menstrual characteristics with these disorders in adolescent girls.
Patients and Methods
This was a cross sectional study. A sample of adolescent school girls aged between 14 and 19 years were included in the study. Diagnostic assessments were based on Premenstrual Assessment Scale (PAS). The data were analyzed in a descriptive fashion and were compared among subgroups of the study sample. In addition, demographic and menstrual factors associations with premenstrual disorders were assessed.
In all 1379 female students were included in the study. About 99.5 % of the students reported at least one premenstrual symptom. Of these, 66.3% was mild, 31.4% moderate and 2.3% severe. A total of 814 girls (59%) met the diagnostic criteria for premenstrual dysphoric disorder (PMDD). Most frequently reported symptoms were back pain, lethargy, fatigue and anxiety. Early menarche, lower education was associated with higher scores on PAS.
Premenstrual disorders are common in adolescent girls. Preventive and treatment strategies are highly recommended.
PMCID: PMC3918194  PMID: 24578837
Premenstrual Syndrome; Depressive Disorder; Prevalence, Dysmenorrhea
3.  Update on Research and Treatment of Premenstrual Dysphoric Disorder 
Harvard review of psychiatry  2009;17(2):120-137.
Many women in their reproductive years experience some mood, behavioral. or physical symptoms in the week prior to menses. Variability exists in the level of symptom burden in that some women experience mild symptoms, whereas a small minority experience severe and debilitating symptoms. For an estimated 5%–8% of premenopausal women, work or social functioning are affected by severe premenstrual syndrome. Many women in this group meet diagnostic criteria for premenstrual dysphoric disorder (PMDD). Among women who suffer from PMDD, mood and behavioral symptoms such as irritability, depressed mood, tension, and labile mood dominate. Somatic complaints, including breast tenderness and bloating, also can prove disruptive to women's overall functioning and quality of life. Recent evidence suggests that individual sensitivity to cyclical variations in levels of gonadal hormones may predispose certain women to experience these mood, behavioral, and somatic symptoms. Treatments include: antidepressants of the serotonin reuptake inhibitor class, taken intermittently or throughout the menstrual cycle; medications that suppress ovarian cyclicity; and newer oral contraceptives with novel progestins. (Harv Rev Psychiatry 2009;17:120–137.)
PMCID: PMC3098121  PMID: 19373620
mood disorders; premenstrual dysphoric disorder; premenstrual syndrome
4.  Premenstrual syndrome and premenstrual dysphoric disorder: guidelines for management 
The inclusion of research diagnostic criteria for premenstrual dysphoric disorder (PMDD) in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, recognizes the fact that some women have extremely distressing emotional and behavioural symptoms premenstrually. PMDD can be differentiated from premenstrual syndrome (PMS), which presents with milder physical symptoms, headache, and more minor mood changes. In addition, PMDD can be differentiated from premenstrual magnification of physical or psychological symptoms of a concurrent psychiatric or medical disorder. As many as 75% of women with regular menstrual cycles experience some symptoms of PMS, according to epidemiologic surveys. PMDD is much less common; it affects only 3% to 8% of women in this group. The etiology of PMDD is largely unknown, but the current consensus is that normal ovarian function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system and other target organs. The serotonergic system is in a close reciprocal relation with the gonadal hormones and has been identified as the most plausible target for interventions. Thus, beyond conservative treatment options such as lifestyle and stress management, other non-antidepressant treatments, or the more extreme intervneitons that eliminate ovulation altogether, selective serotonin reuptake inhibitors (SSRIs) are emerging as the most effective treatment option. Results from several randomized, placebo-controlled trials in women with PMDD have clearly demonstrated that SSRIs have excellent efficacy and minimal side effects. More recently, several preliminary studies indicate that intermittent (premenstrual only) treatment with selective SSRIs is equally effective in these women and, thus, may offer an attractive treatment option for a disorder that is itself intermittent.
PMCID: PMC1408015  PMID: 11109297
5.  Neuroimaging Evidence of Cerebellar Involvement in Premenstrual Dysphoric Disorder 
Biological psychiatry  2010;69(4):374-380.
Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder.
We used positron emission tomography with [18F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological endpoint was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations.
There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD, but not comparison subjects, showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = 0.003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = 0.018).
These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD.
PMCID: PMC3053132  PMID: 21092938
premenstrual dysphoric disorder; premenstrual syndrome; positron emission tomography; fluorodeoxyglucose; cerebellum; neuroimaging
6.  Changes in Mood, Cognitive Performance and Appetite in the Late Luteal and Follicular Phases of the Menstrual Cycle in Women With and Without PMDD (Premenstrual Dysphoric Disorder) 
Hormones and behavior  2008;54(1):185-193.
Although it’s been reported that women with premenstrual dysphoric disorder (PMDD) have increased negative mood, appetite (food cravings and food intake), alcohol intake and cognitive deficits premenstrually, few studies have examined these changes concurrently within the same group of women or compared to women without PMDD. Thus, to date, there is not a clear understanding of the full range of PMDD symptoms. The present study concurrently assessed mood and performance tasks in 29 normally cycling women (14 women who met DSM-IV criteria for PMDD and 15 women without PMDD). Women had a total of ten sessions: two practice sessions, 4 sessions during the follicular phase and 4 sessions during the late luteal phase of the menstrual cycle. Each session, participants completed mood and food-related questionnaires, a motor coordination task, performed various cognitive tasks and ate lunch. There was a significant increase in dysphoric mood during the luteal phase in women with PMDD compared to their follicular phase and compared to Control women. Further, during the luteal phase, women with PMDD showed impaired performance on the Immediate and Delayed Word Recall Task, the Immediate and Delayed Digit Recall Task and the Digit Symbol Substitution Test compared to Control women. Women with PMDD, but not Control women, also showed increased desire for food items high in fat during the luteal phase compared to the follicular phase and correspondingly, women with PMDD consumed more calories during the luteal phase (mostly derived from fat) compared to the follicular phase. In summary, women with PMDD experience dysphoric mood, a greater desire and actual intake of certain foods and show impaired cognitive performance during the luteal phase. An altered serotonergic system in women with PMDD may be the underlying mechanism for the observed symptoms; correspondingly, treatment with specific serotonin reuptake inhibitors (SSRIs) remains the preferred treatment at this time.
PMCID: PMC2491904  PMID: 18413151
Cognitive Performance; Food; PMDD; Mood; Women
7.  Treatment of depression associated with the menstrual cycle: premenstrual dysphoria, postpartum depression, and the perimenopause 
Several forms of depression are unique to women because of their apparent association with changes in gonadal hormones, which in turn modulate neuroregulatory systems associated with mood and behavior. This review examines the evaluation and treatment of depression that occurs premenstrually, postpartum, or in the perimenopause on the basis of current literature. The serotonergic antidepressants consistently show efficacy for severe premenstrual syndromes (PMSs) and premenstrual dysphoric disorder (PMDD), and are the first-line treatment for these disorders. The use of antidepressants for postpartum depression is compromised by concerns for effects in the infants of breast-feeding mothers, but increasing evidence suggests the relative safety of the antidepressant medications, and the risk calculation should be made on an individual basis. Estradiol may be effective for postpartum depression and for moderate-to-severe major depression in the perimenopause. In spite of its frequent use, progesterone is not effective for the mood and behavioral symptoms of PMS/PMDD, postpartum depression, or perimenopausal depressive symptoms.
PMCID: PMC3181677  PMID: 22033555
depression; premenstrual syndrome; postpartum depression; perimenopause; antidepressant; estrogen; gonadal hormone; treatment
Depression and anxiety  2012;29(6):531-540.
Selective serotonin reuptake inhibitors (SRIs) relieve irritability within days in women with premenstrual dysphoric disorder (PMDD); however, the effects on other affective symptoms in PMDD remain to be demonstrated.
We performed hourly ratings in women with PMDD to test the specificity of the therapeutic effects of SRIs and to determine whether the kinetics of these effects differ from those of the symptom offset accompanying menses. Twelve women with PMDD received fluoxetine (20 mg daily) during the luteal phase of the menstrual cycle. Twelve other women with PMDD received no treatment. Outcome measures included a visual analogue scale completed hourly before and after either the start of SRIs or at menses-onset in the untreated women and the premenstrual tension syndrome (PMTS) scale completed daily. Data were analyzed by ANOVA-R.
Hourly VAS scores significantly improved after SRI in irritability as well as sadness, anxiety, and mood swings. Compared with the symptomatic pretreatment baseline, PMTS scores significantly improved on the second day after the start of SRI (p < .01). An identical time course of symptom improvement occurred after both SRI and menses-onset.
Conclusion and Discussion
These data document that the rapid response to SRI was not limited to irritability. The similar kinetics in the remission of PMDD after SRIs and after menses-onset suggest both a phenotype reflecting the relative capacity to rapidly change affective state, and a possible therapeutic mechanism by which SRIs recruit this endogenous capacity to change state, normally expressed around menses-onset in women with PMDD.
PMCID: PMC3442940  PMID: 22565858
premenstrual dysphoric disorder; fluoxetine; selective serotonin reuptake inhibitors; treatment response
9.  Premenstrual symptoms in young adults born preterm at very low birth weight - from the Helsinki Study of Very Low Birth Weight Adults 
BMC Women's Health  2011;11:25.
Clinically significant premenstrual symptoms are common among young women. Premenstrual syndrome (PMS) is characterized by emotional, behavioural and physical symptoms that consistently occur during the luteal phase of the menstrual cycle. Premenstrual dysphoric disorder (PMDD) is a severe form of PMS. Individual variation in stress responsiveness may be involved in the pathophysiology of premenstrual symptoms. Preterm birth at very low birth weight (VLBW, < 1500g) has a multitude of consequences that extend to adult life, including altered stress responsiveness which could affect the prevalence of premenstrual symptoms.
In this cohort study, we compared 75 VLBW women with 95 women born at term (mean age 22.5). We used a standardized retrospective questionnaire assessing the presence and severity of a variety of symptoms before and after menses. The symptom scores were used both as continuous and as dichotomized variables, with cutoffs based on DSM-IV criteria for PMDD and ACOG criteria for PMS, except prospective daily ratings could not be used. We used multiple linear and logistic regression to adjust for confounders.
There was no difference in the continuous symptom score before menses (mean difference VLBW-term -18.3%, 95% confidence interval -37.9 to 7.5%) or after menses. The prevalence of premenstrual symptoms causing severe impairment to daily life was 13.3% for VLBW women and 14.7% for control women. For PMDD, it was 8.0% and 4.2%, and for PMS, 12.0% and 11.6%, respectively. These differences were not statistically significant (p > 0.1).
Our findings suggest that the severity of premenstrual symptoms and the prevalence of PMDD and PMS among young women born preterm at VLBW is not higher than among those born at term.
PMCID: PMC3127835  PMID: 21639914
10.  Premenstrual syndrome 
Lancet  2008;371(9619):1200-1210.
Most women of reproductive age have some physical discomfort or dysphoria in the weeks before menstruation. Symptoms are often mild, but can be severe enough to substantially affect daily activities. About 5–8% of women thus suffer from severe premenstrual syndrome (PMS); most of these women also meet criteria for premenstrual dysphoric disorder (PMDD). Mood and behavioural symptoms, including irritability, tension, depressed mood, tearfulness, and mood swings, are the most distressing, but somatic complaints, such as breast tenderness and bloating, can also be problematic. We outline theories for the underlying causes of severe PMS, and describe two main methods of treating it: one targeting the hypothalamus-pituitary-ovary axis, and the other targeting brain serotonergic synapses. Fluctuations in gonadal hormone levels trigger the symptoms, and thus interventions that abolish ovarian cyclicity, including long-acting analogues of gonadotropin-releasing hormone (GnRH) or oestradiol (administered as patches or implants), effectively reduce the symptoms, as can some oral contraceptives. The effectiveness of serotonin reuptake inhibitors, taken throughout the cycle or during luteal phases only, is also well established.
PMCID: PMC3118460  PMID: 18395582
11.  Premenstrual dysphoric disorder: burden of illness and treatment update 
Five percent of menstruating women have severe premenstrual symptoms and impairment of functioning defined as premenstrual dysphoric disorder (PMDD). Clinically significant premenstrual symptoms occur in at least an additional 20% of menstruating women. The diagnosis of PMDD should be confirmed by prospective symptom charting over 2 menstrual cycles to confirm the timing of the symptoms and to rule out other diagnoses. The burden of illness of PMDD includes disruption of parenting and partner relationships and decreased productivity in work roles. In addition, women with PMDD have increased use of health care services such as clinician visits and increased use of prescription medications and over-the-counter preparations. The etiology of PMDD is multifactorial. In particular, dysregulation of the serotonin and allopregnanolone systems is implicated. Several effective treatment options exist, including serotonergic antidepressant medications and an oral contraceptive that contains ethinyl estradiol and drosperinone. In addition, other hormones that suppress ovulation, anxiolytics, cognitive therapy, chasteberry and calcium may be helpful.
PMCID: PMC2440788  PMID: 18592027
premenstrual syndrome; contraceptives, oral; serotonin uptake inhibitors; treatment
12.  Prefrontal Brain Asymmetry and Pre-Menstrual Dysphoric Disorder Symptomatology 
Journal of affective disorders  2010;128(1-2):178-183.
Premenstrual dysphoric disorder (PMDD), a dysphoric form of premenstrual syndrome, is included as a diagnosis for further study in the DSM-IV-TR (APA, 2000). The present study investigated whether a marker of risk for Major Depressive Disorder (MDD), prefrontal brain asymmetry, also characterizes women with PMDD.
In a sample of 25 college women with PMDD symptomatology and 25 matched controls, resting frontal electroencephalographic (EEG) activity was assessed on four occasions within a two-week span.
Across several frontal sites women with PMDD had relatively less left than right prefrontal brain activity, consistent with a diathesis-stress model for menstrual-related dysphoria.
The findings suggest an overlap in the risk profile for MDD and PMDD.
PMCID: PMC2994967  PMID: 20833433
EEG asymmetry; premenstrual dysphoria; risk; diathesis
13.  Neuroticism-related personality traits are related to symptom severity in patients with premenstrual dysphoric disorder and to the serotonin transporter gene-linked polymorphism 5-HTTPLPR 
Archives of Women's Mental Health  2010;13(5):417-423.
Neuroticism has been linked to a functional polymorphism in the serotonin transporter gene (5-HTTLPR), with short-allele carriers being overrepresented among high-scorers on neuroticism. Studies evaluating neuroticism-related personality traits in relation to the 5-HTTLPR polymorphism among patients with premenstrual dysphoric disorder (PMDD) and are lacking. The primary aim of this study was to evaluate the relationship between PMDD and neuroticism-related personality traits, and secondly, to relate the personality trait scores of PMDD patients to experienced symptom severity and to the 5-HTTLPR short allele. Thirty PMDD patients and 55 asymptomatic healthy controls were included in the study. The Swedish Universities Scale of Personality was used to evaluate personality traits. Genotype analyses were available in 27 PMDD patients and 18 healthy controls. Women with PMDD displayed higher levels of neuroticism-related personality traits (psychic trait anxiety, somatic trait anxiety, embitterment, stress susceptibility and mistrust) than healthy controls, and these effects were most prominent in women with more severe luteal phase symptoms. Furthermore, PMDD patients with at least one copy of the short allele of the 5-HTTLPR polymorphism scored higher on psychic trait anxiety and lack of assertiveness than PMDD patients who were homozygous for the long allele. PMDD patients who suffer from more severe luteal phase symptoms also display increased scores of neuroticism-related personality traits in comparison with healthy controls. Within the group of PMDD patients, differences in certain personality trait scores are associated with the short allele of the 5-HTTLPR polymorphism.
PMCID: PMC2941046  PMID: 20440524
Personality; Neuroticism; Premenstrual dysphoric disorder; Swedish universities scale of personality; 5-HTTPLPR
14.  Lifetime Discrimination Associated with Greater Likelihood of Premenstrual Dysphoric Disorder 
Journal of Women's Health  2011;20(6):923-931.
To evaluate whether the stressor of perceived discrimination was associated with premenstrual dysphoric disorder (PMDD) and premenstrual symptoms among minority women. This study builds on previous research that found perceived discrimination was positively associated with other psychiatric illnesses.
Participants were 2718 Asian, Latina, and black premenopausal women aged 18–40 years who completed the World Mental Health Composite International Diagnostic Interview for the National Latino and Asian American Survey or the National Survey of American Life. Perceived discrimination was assessed with the Everyday Discrimination Scale. DSM-IV-based diagnostic algorithms generated a provisional lifetime diagnosis of PMDD.
Eighty-three percent of the participants reported experiencing discrimination (due to race, gender, age, height or weight, or other reasons) in their lifetimes. The frequency of perceived discrimination was positively associated with PMDD (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05-1.10) and premenstrual symptoms (OR 1.04, 95% CI 1.02-1.05), independent of demographic covariates and social desirability. Women reporting gender discrimination (OR 5.18, 95% CI 1.80-14.90), race discrimination (OR 4.14, 95% CI 1.54-11.11), and other forms of discrimination (OR 6.43, 95% CI 2.11-19.65) were significantly more likely than women without experiences of discrimination to have PMDD. Subtle discrimination was more strongly associated with PMDD (OR 1.12, 95% CI 1.01-1.23) than was blatant discrimination (OR 1.04, 95% CI 0.94-1.15).
This study is the first to demonstrate that perceived discrimination is associated with PMDD and premenstrual symptoms. These findings suggest that the prevalence of these conditions may be lessened by reducing discrimination in women's lives.
PMCID: PMC3159126  PMID: 21671777
15.  Low-Dose Acetazolamide in the Treatment of Premenstrual Dysphoric Disorder: A Case Series 
Psychiatry Investigation  2014;11(1):95-101.
The treatment of premenstrual dysphoric disorder (PMDD) is far from satisfactory, as there is a high proportion of patients who do not respond to conventional treatment. The antidiuretic sulfonamide, acetazolamide, inhibits carbonic anhydrase and potentiates GABAergic transmission; the latter is putatively involved in PMDD. We therefore tried acetazolamide in a series of women with intractable PMDD. Here, we describe a series of eight women diagnosed with DSM-IV-TR PMDD, five of whom had comorbidity with a mood disorder and one with an anxiety disorder, who were resistant to treatment and responded with symptom disappearance after being added-on 125 mg/day acetazolamide for 7-10 days prior to menses each month. Patients were free from premenstrual symptoms at the 12-month follow-up. We suggest that acetazolamide may be used to improve symptoms of PMDD in cases not responding to other treatments. GABAergic mechanisms may be involved in counteracting PMDD symptoms.
PMCID: PMC3942558  PMID: 24605130
Premenstrual dysphoric disorder; Sulfonamide diuretics; Acetazolamide; GABA transmission
16.  Elevated Gray Matter Volume of the Emotional Cerebellum in Women with Premenstrual Dysphoric Disorder Disorder 
Journal of affective disorders  2012;146(2):266-271.
Premenstrual dysphoric disorder (PMDD) is characterized by severe, negative mood symptoms during the luteal phase of each menstrual cycle. We recently reported that women with PMDD show a greater increase in relative glucose metabolism in the posterior cerebellum from the follicular to the luteal phase, as compared with healthy women, and that the phase-related increase is proportional to PMDD symptom severity. We extended this work with a study of brain structure in PMDD.
High-resolution magnetic resonance imaging (MRI) scans were obtained from 12 women with PMDD and 13 healthy control subjects (whole-brain volume-corrected p<.05). Voxel-based morphometry was used to assess group differences in cerebral grey-matter volume (GMV), using a statistical criterion of p<.05, correcting for multiple comparisons in the whole-brain volume.
PMDD subjects had greater GMV than controls in the posterior cerebellum but not in any other brain area. Age was negatively correlated with GMV within this region in healthy women, but not in women with PMDD. The group difference in GMV was significant for women over age 30 (p=.0002) but not younger participants (p>.1).
PMDD appears to be associated with reduced age-related loss in posterior cerebellar GMV. Although the mechanism underlying this finding is unclear, cumulative effects of symptom-related cerebellar activity may be involved.
PMCID: PMC3529750  PMID: 22868063
premenstrual dysphoric disorder; premenstrual syndrome; cerebellum; neuroimaging; voxel-based morphometry; brain aging
17.  The prevalence of premenstrual dysphoric disorder in a randomly selected group of urban and rural women 
Psychological medicine  2008;39(1):129-136.
Premenstrual dysphoric disorder (PMDD) was included as a provisional diagnostic category in the appendices of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R (then called late luteal phase dysphoric disorder) and remained as an appendix in DSM-IV. Our study aimed to determine the prevalence of PMDD using all four DSM-IV research diagnostic criteria in a representative sample of women of reproductive age in the United States.
Data were collected in the homes of women between the ages of 13 and 55 years in two urban and two rural sites using a random sampling procedure developed by the National Opinion Research Center. Women completed daily symptom questionnaires and provided urine specimens each day for two consecutive ovulatory menstrual cycles (ovulation was estimated for women taking oral contraceptives) and were screened for psychiatric disorders by trained interviewers. Symptoms were counted toward a diagnosis of PMDD if they worsened significantly during the late luteal week during two consecutive ovulatory menstrual cycles, occurred on days in which women reported marked interference with functioning, and were not due to another mental disorder.
In the final analysis, 1246 women who had had at least one menstrual cycle and were neither naturally nor surgically menopausal nor pregnant were selected. Of the women in the study, 1.3% met criteria for the diagnosis as defined in DSM-IV.
The prevalence of PMDD is considerably lower than DSM-IV estimates and all but one of the estimates obtained from previous studies when all DSM-IV diagnostic criteria are considered. We suggest a new process for diagnosing PMDD based on our findings.
PMCID: PMC2752820  PMID: 18366818
Premenstrual dysphoric disorder; prevalence
18.  The Relationship between Severity of Premenstrual Syndrome and Psychiatric Symptoms 
Iranian Journal of Psychiatry  2012;7(1):36-40.
Premenstrual syndrome is a common disorder experienced by up to 50% of women during reproductive age. The prevalence of severe form of PMS (PMDD) is 3% to 8 %. Psychiatric disorders in PMS patients have resulted in significant morbidity and in some cases caused resistance to the treatment process.
Material and Method
390 participants (264 with PMS/PMDD, and 126 healthy students of University of Guilan) who completed the demographic questionnaire, daily symptom rating (DSR) and the checklist 90-revised (SCL-90-R) took part in this study. This study was conducted using a cross sectional method.
According to repeated measure variance, the mean scores of psychiatric symptoms (Depression, Anxiety, Aggression, Interpersonal sensitivity) in the PMS group were significantly higher than the healthy group (p< 0/05), and increase in severity of PMS from mild to severe was accompanied by increase in mean score of these subscales. There was a significant difference in mean score of depression, anxiety, aggression and interpersonal sensitivity between the 3rd and the 13th day of the cycle. Significant effect of the DSR grouping (PMS and Healthy group) and time interaction emerged in interpersonal sensitivity and aggression, significant effect on the DSR grouping (Mild, Moderate, Severer) and time interaction demonstrated in interpersonal sensitivity.
Patients with prospective confirmed PMDD seemed to suffer from psychiatric symptoms. Therefore, recognizing co-morbid psychiatric symptoms in patients with PMDD is of prime importance. All healthcare providers should be sensitive to mental status of women with PMS.
PMCID: PMC3395966  PMID: 23056116
Premenstrual syndrome; Psychiatric symptoms; Severity of illness
19.  Timing of Alcohol Use and the Incidence of Premenstrual Syndrome and Probable Premenstrual Dysphoric Disorder 
Journal of Women's Health  2009;18(12):1945-1953.
Relatively little is known about factors that influence the initial development of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), although these conditions are common in reproductive age women and are associated with substantial impairment. Previous studies have observed higher alcohol use in prevalent PMS/PMDD patients compared with controls, but it is unknown if drinking predisposes women to developing these disorders or is instead influenced by symptom experience.
To address this, we conducted a case-control study nested within the prospective Nurses' Health Study II (NHS2). Participants were a subset of women aged 27–44 and free from PMS at baseline (1991), including 1057 women who developed PMS over 10 years of follow-up, 762 of whom also met criteria consistent with PMDD, and 1968 control women. Alcohol use at various time periods, before and after onset of menstrual symptoms, was assessed by questionnaire.
Overall, alcohol use was not strongly associated with the incidence of PMS and probable PMDD. Relative risks (RR) for women with the highest cumulative alcohol use vs. never drinkers were 1.19 (95% confidence interval [CI] 0.84-1.67) for PMS and 1.28 (95% CI 0.86-1.91) for PMDD, although results did suggest a positive relationship in leaner women (p trend = 0.002). Women who first used alcohol before age 18 had an RR of PMS of 1.26 (95% CI 0.91-1.75) compared with never drinkers; the comparable RR for PMDD was 1.35 (95% CI 0.93-1.98).
These findings suggest alcohol use is not strongly associated with the development of PMS and PMDD, although early age at first use and long-term use may minimally increase risk.
PMCID: PMC2828255  PMID: 20044856
20.  Late, but not early, wake therapy reduces morning plasma melatonin: relationship to mood in premenstrual dysphoric disorder 
Psychiatry research  2008;161(1):76-86.
Wake therapy improves mood in Premenstrual Dysphoric Disorder (PMDD), a depressive disorder in DSM-IV. We tested the hypothesis that the therapeutic effect of wake therapy in PMDD is mediated by altering sleep phase with melatonin secretion.
We measured plasma melatonin every 30 minutes (18:00 - 09:00 h) in 19 PMDD and 18 normal control (NC) women during mid follicular (MF) and late luteal (LL) menstrual cycle phases, and during LL interventions with early wake therapy (EWT) (sleep 03:00–07:00 h)(control condition) versus late wake therapy (LWT) (sleep 21:00-01:00 h)(active condition).
Melatonin offset was delayed and duration was longer in the symptomatic LL vs. asymptomatic MF phase in both NC and PMDD subjects. LWT, but not EWT, advanced offset and shortened duration vs. the LL baseline, although they improved mood equally. Later baseline LL morning melatonin offset was associated with more depressed mood in PMDD patients, and longer melatonin duration in the MF phase predicted greater mood improvement following LWT.
That LWT, but not EWT, advanced melatonin offset and shortened duration while they were equally effective in improving mood suggests that decreasing morning melatonin secretion is not necessary for the therapeutic effects of wake therapy in PMDD.
PMCID: PMC3038844  PMID: 18789826
Sleep deprivation; circadian rhythms; affective disorders; reproduction
21.  Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder 
Premenstrual dysphoric disorder (PMDD) is estimated to affect 3%–8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs) were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 μg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality.
PMCID: PMC2971718  PMID: 21072278
drospirenone; premenstrual dysphoric disorder; premenstrual syndrome; oral contraceptive pill
22.  Health related quality of life among adolescents with premenstrual disorders: a cross sectional study 
Premenstrual disorders usually refer to premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). This study was designed to evaluate health-related quality of life (HRQOL) in a sample of Iranian adolescents with premenstrual disorders.
This was a cross sectional study. A sample of adolescent schoolgirls aged between 14 and 19 years were included in the study. Premenstrual disorders were indicated according to the International Classification of Diseases (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Health-related quality of life was measured using the Short Form Health Survey (SF-36). The data were analyzed in a descriptive fashion and were compared among subgroups of the study sample.
In all 602 female students were studied. All students reported at least one premenstrual symptom. Of these, 224 (37.2%) met the diagnostic criteria for premenstrual dysphoric disorder (PMDD). Comparing the SF-36 scores between female students with and without PMDD, it was found that there were significant differences between these two groups in all measures (P < 0.001) except for physical functioning (P = 0.274). These differences were more evident on role emotional, role physical, social functioning and bodily pain.
The study findings affirm the fact that adolescents with premenstrual disorders suffer from poor health-related quality of life. In order to improve quality of life in female adolescents appropriate support should be provided for this population especially for those who suffer from more severe premenstrual disorders.
PMCID: PMC3281794  PMID: 22208808
23.  Pilot Investigation of the Circadian Plasma Melatonin Rhythm across the Menstrual Cycle in a Small Group of Women with Premenstrual Dysphoric Disorder 
PLoS ONE  2012;7(12):e51929.
Women with premenstrual dysphoric disorder (PMDD) experience mood deterioration and altered circadian rhythms during the luteal phase (LP) of their menstrual cycles. Disturbed circadian rhythms may be involved in the development of clinical mood states, though this relationship is not fully characterized in PMDD. We therefore conducted an extensive chronobiological characterization of the melatonin rhythm in a small group of PMDD women and female controls. In this pilot study, participants included five women with PMDD and five age-matched controls with no evidence of menstrual-related mood disorders. Participants underwent two 24-hour laboratory visits, during the follicular phase (FP) and LP of the menstrual cycle, consisting of intensive physiological monitoring under “unmasked”, time-isolation conditions. Measures included visual analogue scale for mood, ovarian hormones, and 24-hour plasma melatonin. Mood significantly (P≤.03) worsened during LP in PMDD compared to FP and controls. Progesterone was significantly (P = .025) increased during LP compared to FP, with no between-group differences. Compared to controls, PMDD women had significantly (P<.05) decreased melatonin at circadian phases spanning the biological night during both menstrual phases and reduced amplitude of its circadian rhythm during LP. PMDD women also had reduced area under the curve of melatonin during LP compared to FP. PMDD women showed affected circadian melatonin rhythms, with reduced nocturnal secretion and amplitude during the symptomatic phase compared to controls. Despite our small sample size, these pilot findings support a role for disturbed circadian rhythms in affective disorders. Possible associations with disrupted serotonergic transmission are proposed.
PMCID: PMC3526531  PMID: 23284821
24.  Premenstrual Dysphoric Disorder as a correlate of suicidal ideation, plans, and attempts among a nationally representative sample 
Suicide is a major public health concern and a leading cause of death in the United States. Psychopathology is an established risk factor for non-fatal suicidal behavior; however, it is unclear whether Premenstrual Dysphoric Disorder (PMDD), a psychiatric disorder specific to women, is correlated with these outcomes. The objective of this study was to determine if PMDD status was associated with suicidal ideation, plans, and attempts, independently of socio-demographic factors and psychiatric comorbidity.
We conducted a secondary data analysis of 3,965 American women aged 18–40 who participated in the Collaborative Psychiatric Epidemiology Survey. Descriptive statistics and forward stepwise logistic regression modeling were performed using SUDAAN software.
The prevalence of non-fatal suicidal behaviors increased in a graded fashion according to PMDD status. Although control for demographic characteristics and psychiatric comorbidity greatly attenuated the unadjusted association between PMDD and suicidal behaviors, women with PMDD remained significantly more likely than women with no premenstrual symptoms to report suicidal ideation (OR=2.22; 95% CI=1.40–3.53), plans (OR=2.27; 95% CI=1.20–4.28), and attempts (OR=2.10; 95% CI=1.08–4.08). Only the likelihood of suicidal ideation was significantly elevated among women with moderate/severe PMS (OR=1.49; 95% CI=1.17–1.88) compared to women with no premenstrual symptoms.
PMDD was strongly and independently associated with non-fatal suicidal behaviors among a nationally representative sample. These findings suggest that clinicians treating women with PMDD should assess and be vigilant for signs of non-fatal suicidal behavior, and that clinicians evaluate and treat the premenstrual symptoms of women who express these behaviors.
PMCID: PMC3774023  PMID: 22752111
Premenstrual Dysphoric Disorder; non-fatal suicidal behavior; epidemiology
25.  Facial Emotion Discrimination Across the Menstrual Cycle in Women with Premenstrual Dysphoric Disorder (PMDD) and Controls 
Journal of affective disorders  2007;104(1-3):37-44.
Depressed patients show mood-congruent errors in the identification of emotion in facial expressions. Errors consist of impaired performance (recognition errors) and negative bias (seeing faces as sadder than they are). This abnormal processing may both reflect and contribute to the negative affective state. In this study, we administered an emotional recognition in facial expression task to women with premenstrual dysphoric disorder (PMDD) to determine whether processing errors similar to those in depression were present and whether they were confined to the luteal phase (i.e., state dependent).
The Facial Discrimination Task (FDT) was administered in the follicular and luteal phases to women with PMDD (n = 28) and asymptomatic controls (n = 27).
ANOVA with repeated measures identified significantly increased negative judgments (both performance errors and bias) in women with PMDD during the luteal phase (more neutral to sad misjudgments and higher negative bias index) as well as impaired “specificity” of judgments [an inability to discriminate neutral from emotional stimuli] (diagnosis by phase interactions, p <.05), findings similar to those observed in depression. No menstrual cycle effects were seen in controls, and no differences between patients and controls were seen on a control task (age assessment of pictured subjects).
The levels of significance obtained were modest and would not withstand correction for multiple comparisons.
Women with PMDD display a luteal phase-dependent impairment (negative bias) in the processing of non-verbal affective information. This negative bias may contribute to the generation of negative mood states during the luteal phase and could suggest the presence of dysfunction in those brain regions whose coordinated activity mediates the recognition of emotion in facial expression.
PMCID: PMC2692989  PMID: 17367867

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