Influences of premenstrual syndrome on daily psychological states and salivary cortisol level

The purpose of this study is to investigate the influences of premenstrual syndrome (PMS) on daily psychological states and salivary cortisol level. First, 42 women recorded their PMS symptoms and basal body temperatures every day for approximately two menstrual cycles. Based on these prospective records of PMS symptoms, participants were divided into two groups: Normal group (n=22) and PMS group (n=17). There were no significant differences between the two groups in age, height, weight, age at menarche, menstrual cycle length, menstrual period, depression score, and stressor score. Next, 14 women (7 Normal group, 7 PMS group) were selected and they were measured twice, once during the premenstrual phase and once during the postmenstrual phase of their cycles. Each day, they took saliva samples and recorded their psychological states six times (from waking to going to bed) per day at their homes. Results showed that the fear score in PMS group was high in the premenstrual phase, whereas salivary cortisol level in PMS group was low in the same phase compared to the Normal group. These results suggested the possibility of dysregulation of the stress system in women with PMS.     

Daytime sleepiness, psychomotor performance, waking EEG spectra and evoked potentials in women with severe premenstrual syndrome

We assessed daytime sleepiness using objective and subjective measures in women with severe premenstrual syndrome (PMS) compared with women without significant premenstrual symptoms. Nine women with severe PMS and eight controls (aged 18−40 years) completed a laboratory-based daytime protocol including the maintenance of wakefulness test (MWT), psychomotor vigilance task (PVT), quantitative waking electroencephalogram (EEG), auditory and visual event-related potentials (ERPs), and sleepiness and mood scales during the mid-follicular and late-luteal (premenstrual) phases of the menstrual cycle. In association with increased perceived sleepiness, fatigue and other premenstrual symptoms in the late-luteal phase, women with PMS performed more poorly on the PVT, with increased lapses and slower reaction times ( P  <   0.05), compared with the follicular phase and controls. However, there were no significant group or menstrual phase differences in latency to sleep on the MWT. Waking spectral EEG power and ERP measures also did not differentiate PMS women when symptomatic. Both groups of women displayed increased spectral power in the delta/theta frequencies (2−6 Hz) and fast alpha frequency (11−12 Hz) in the late-luteal phase relative to the follicular phase. Trait-like differences were apparent in that women with PMS had increased beta1 (12−16 Hz) power and smaller P300 amplitude than controls in both menstrual cycle phases. Our findings indicate that women with severe PMS are subjectively sleepy and fatigued, and show psychomotor slowing when symptomatic compared with when they are symptom-free and compared with controls. However, the ability to maintain wakefulness under soporific conditions, spectral properties of waking EEG and cognitive processing do not vary in synchrony with premenstrual symptoms.     

Plasma leptin concentrations are increased in women with premenstrual syndrome

Leptin is a metabolic regulator of the hypothalamic- pituitary-gonadal axis, and plays an important role in human reproduction. Its neuro-endocrine effects are mediated by interactions with receptors in the hypothalamus, where emotional drive is also controlled. We postulated that circulating leptin concentrations are increased in premenstrual syndrome (PMS), and that this may be associated with the psychological symptoms of the disease. We obtained fasting venous samples from 32 women with PMS and 28 women with asymptomatic menstrual cycles, matched for age, body mass index and menstrual cycle length. Leptin concentrations were measured by radioimmunoassay. Leptin concentrations increased significantly during the luteal phases of the menstrual cycles of the control and PMS groups as compared with the follicular phase, having excluded the 11 women with PMS and six controls found to be anovulatory on the basis of mid-luteal plasma progesterone concentrations from the analysis. A greater increase was observed in women with PMS than the controls (P: = 0.00006 and 0.003 respectively). Although leptin concentrations in the follicular and luteal phases were higher in PMS than the controls, the difference was only statistically significant between the follicular phases (P: = 0.001). There was no clear relationship between leptin and oestradiol or progesterone in this study. These findings suggest that leptin may play a role in the pathophysiology of the disease, and requires further evaluation.     

Sleep quality and the sleep electroencephalogram in women with severe premenstrual syndrome

STUDY OBJECTIVES: Women with severe premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) commonly report sleep disturbances, but the few studies using conventional polysomnographic measures have produced conflicting results. We investigated sleep quality and sleep composition using conventional and quantitative electroencephalographic analyses in women with severe PMS, as compared with that of controls. DESIGN AND PARTICIPANTS: Women (aged 18-40 years) were screened to ensure that their PMS symptoms were severe and that they had ovulatory menstrual cycles. Nine women with PMS or PMDD and 12 asymptomatic control subjects then had laboratory-based polysomnographic recordings at 2 phases of the menstrual cycle: follicular phase and late luteal (premenstrual) phase. RESULTS: Women with severe PMS reported a significantly poorer subjective sleep quality during the late luteal phase (P = 0.02), but there was no evidence of disturbed sleep based on the polysomnogram specific to premenstrual symptom expression: both groups of women had increased wakefulness after sleep onset (P = 0.02) and increased sigma power (P < 0.01), especially in the 14-to 15-Hz band during non-rapid eye movement sleep, in the late luteal phase compared with the follicular phase. There were, however, some group differences in electroencephalographic measures regardless of menstrual phase, including decreased delta incidence (P = 0.02) and increased theta incidence and amplitude (P < 0.05) in women with PMS, suggesting the possibility of sleep electroencephalogram trait markers in women with PMS. CONCLUSION: Perceived poor quality sleep is a characteristic of severe PMS, but sleep composition based on polysomnographic measures and quantitative electroencephalographic analysis does not differ in association with premenstrual symptom expression in the late luteal phase.     

Lack of effect of induced menses on symptoms in women with premenstrual syndrome

BACKGROUND. No physiologic abnormality of the luteal phase has been consistently demonstrated in women with premenstrual syndrome (PMS). Using the progesterone antagonist mifepristone, we truncated the late luteal phase of the menstrual cycle in a blinded fashion to evaluate the relation of the events of the late luteal phase to the symptoms of PMS. METHODS. Fourteen women with PMS were given mifepristone (12.5 or 25 mg per kilogram of body weight) by mouth on the seventh day after the surge of luteinizing hormone. On the sixth through the eighth days after the surge, they also received injections of either placebo or human chorionic gonadotropin (2000 IU). Seven women with PMS received placebo instead of both mifepristone and human chorionic gonadotropin. All the women completed daily questionnaires measuring a variety of mood-related and somatic symptoms. RESULTS. Mifepristone consistently induced menses. The women receiving only mifepristone had plasma progesterone levels like those of the follicular phase (less than 3 nmol per liter) within four days, whereas all the other women had plasma progesterone levels characteristic of the luteal phase (greater than 8 nmol per liter) for at least seven days after treatment. In all three groups, the severity of symptoms was significantly higher after treatment than before, according to an analysis of variance with repeated measures. The level and pattern of the ratings of symptom severity were similar in all treatment groups. CONCLUSIONS. Neither the timing nor the severity of PMS symptoms was altered by mifepristone-induced menses or luteolysis. The temporal association of typical PMS symptoms with an artificially induced follicular phase suggests that endocrine events during the late luteal phase do not directly generate the symptoms of PMS.     

Refractory hypertension in women controlled after identifying and addressing premenstrual syndrome

Control of high blood pressure is usually difficult when there is an unidentified cause or there exist certain factors that blunt the effect of appropriate therapy. Premenstrual syndrome (PMS) is neither a known cause of hypertension nor is it listed as one of the factors that blunt effect of antihypertensives. PMS defines a constellation of symptoms confined to the luteal phase of the menstrual cycle interfering with individual function but clears after menstruation in the follicular phase. Though there is no consensus yet on its etiopathogenesis, the various models, inconsistent as they are, can initiate or sustain hypertension. The two patients presented had been frustrated by the attitude of their attending physicians who branded them neurotics and the fact that various drug combinations would not control their blood pressure. The classical recurring nature of their symptoms in relation to the menstrual cycle led to the suspicion of and treatment of PMS. With this, it became easy to control their erstwhile "refractory" hypertension. It is, therefore, recommended that history of PMS be sought and attended to, when premenopausal women without evidence of secondary hypertension have high blood pressures that proove difficult to control.     

The predictive role of psychosocial stress on symptom severity in premenstrual syndrome

Twenty-five women with well defined, severe premenstrual syndrome (PMS) were studied prospectively during three consecutive menstrual cycles to examine the association between concurrent psychosocial stress and symptom severity. Stress, mood, physical symptoms, and urinary ovarian steroid metabolites were measured daily. Stress accounted for only 6% and 10% of the unique variance in physical symptom and mood scores, respectively, across the menstrual cycle. In individual woman, there was no association between the severity of symptoms and the cumulative daily stress reported during each cycle. We conclude that in this carefully screened population of women without coexisting psychiatric disorder, PMS symptom severity could not be determined by the amount of psychosocial stress.     

Perimenstrual symptoms: time course of symptom intensity in relation to endocrinologically defined segments of the menstrual cycle

This investigation assessed the syndromal nature of menstrual cycle changes in women who experience significant cyclicity of mood by exploring the time course of different symptoms in relation to endocrinologically defined segments of the menstrual cycle. Participants were accepted into the protocol on the basis of a prospectively documented history of perimenstrual mood change. The protocol included completion of the Daily Life Experiences Questionnaire and blood sampling during three menstrual cycles. The syndromal nature of menstrual cycle changes was explored by determining the types of symptoms which fluctuated in relation to five endocrinologically defined segments of the menstrual cycle, and the time course of the symptom changes. The results further document the temporal association between the luteal phase and the onset of perimenstrual symptoms and suggest that the syndromal nature of menstrual cycle-related changes may differ for women who experience different intensities of cyclical mood.     

Pre-menstrual syndrome: a new concept in its pathogenesis and treatment

It is proposed that the normal regulation of the vasodilatation and vascular lengthening during the luteal phase of the menstrual cycle is due to the increased release of endothelial nitric oxide as a result of the maximum oestrogen/progesterone levels as manifest during this phase. Excessive levels of NO have additional systemic effects, and these may present as the pre-menstrual syndrome which classically occurs during the luteal phase of the menstrual cycle.The manufacture of NO is under the control of the enzyme NO synthase. The concentration of the latter can be affected by steroids. The proposed new treatment of PMS is premised on the basis that oral steroids given during the luteal phase will reduce the levels of NO and thus in turn will miminise the signs and symptoms of PMS.     

Serum leptin levels during the menstrual cycle of healthy fertile women.

Leptin is a protein, produced by adipose tissue, which has cytokine and hormonal properties. Serum leptin levels can be considered as a measure of body fat mass, and are involved in regulation of body weight. Previous studies suggest that leptin may have an additional role in reproduction, and there is also evidence for involvement in the hypothalamic-pituitary-gonadal axis. In this study, we investigate the possible changes in serum leptin concentration throughout the menstrual cycle. Samples were collected from apparently healthy, fertile women at different stages in their menstrual cycle, timed precisely according to the luteinising hormone (LH) surge. Mean serum leptin levels were significantly higher in the luteal phase (median 11.4 ng/mL) than in the follicular phase (median 10.0 ng/mL) (P < 0.001). In addition, mean serum leptin levels correlated with body mass index (r = 0.54, P < 0.05), but showed no correlation with luteal-phase progesterone levels. Results showed that levels of serum leptin vary during the menstrual cycle, and add to the mounting evidence that leptin has a role in reproduction. These fluctuations should be taken into account whenever studies are performed using female subjects.     

Skin conductance and heart rate in women with premenstrual syndrome

This study investigated the effects of the menstrual cycle phase on certain components of autonomic arousal and task performance. Premenstrual syndrome (PMS) women and matched controls (non-PMS) were tested both premenstrually and postmenstrually. The conditions selected were a) the presentation of 10 tones, b) a proofreading performance task, and c) a word-association learning task. Skin conductance and heart rate were continuously monitored. No significant effects were found on baseline physiological measures, or on proofreading or word-association performance. A significant point in cycle effect for skin conductance and HR orienting response to the tones was found showing smaller HR and skin conductance responses postmenstrually. Several significant PMS classifications by point in menstrual cycle interactions were found. These indicated that, paradoxically, the non-PMS subjects showed higher spontaneous skin conductance responding during the word association task and higher skin conductance responses to tones prior to menses. While in contrast, PMS subjects yielded higher responding on the same measures postmenstrually. On stress ratings, PMS subjects reported experiencing more stress postmenstrually. Results are discussed in terms of the possible role of expectancy factors and inaccurate self-monitoring.     

Expression of estrogen and progesterone receptors in the endometrium of fertile and infertile women

The aim of the research is investigation of the endometrial hormonal status during menstrual cycle infertile and infertile women. 68 endometrial biopsies from 18-45 years old women have been studied. Some changes of ER and PR expression during menstrual cycle both in fertile and infertile women has been founded. However the ER expression in endometrial stroma and PR in the glands in a proliferative stage of cycle of fertile women are higher than in a secretory stage. In infertile women the PR expression in endometrial glands is opposite.     

Premenstrual symptomatology: role of prior knowledge about premenstrual syndrome

OBJECTIVE: Most women have some premenstrual symptoms that may be influenced by diverse environmental factors. The aim of this study was to determine the influence of knowledge about premenstrual syndrome (PMS) in the reports of women and their symptoms. METHOD: We studied 86 healthy Mexican women whose highest level of education was sixth grade. Participants were assigned to one of two groups. The experimental group watched a videotape describing PMS and its negative consequences in daily life. The control group watched a videotape describing the menstrual cycle. The Menstrual Distress Questionnaire was administered to all women during the first week after menstruation, after which they were shown their designated videotape, and the questionnaire was administered again after the next menstruation. RESULTS: In the control group, there were no significant differences in premenstrual symptoms reported both before and after the women watched the videotape. However, women in the experimental group reported more severe premenstrual symptoms after watching the videotape. CONCLUSIONS: These results suggest that after observing the videotape, women's expectancies of negative symptoms in the premenstrual phase increased. Thus, the symptoms reported by these women were enhanced.     

Electrodermal activity, hormonal levels and subjective experience during the menstrual cycle

Changes in electrodermal activity and subjective experience were studied during the menstrual cycle. Sixty-two women, grouped into menstrual, follicular, ovulatory, luteal and premenstrual phases, were presented with 15, 4-s, 80-dB, 1000-Hz tones. Psychological states and psychosomatic symptoms were tested with Spielberger's State-Trait Anxiety Inventory and a self-report questionnaire. Two estimation procedures of the hormonal phases were used: one based on the onset of menses and cycle length, and another on the basal body temperature. Subjects were grouped into low or high levels of luteinizing hormone, follicle-stimulating hormone and progesterone. There were significant increases in nonspecific response frequency, skin conductance response magnitude, skin conductance level, and a decrease in habituation rate at the ovulatory phase in comparison with luteal and premenstrual phases. No changes between the cycle phases were found in subjective experience. High follicle-stimulating hormone levels were associated with slower habituation rates and low trait-anxiety. The relationship between arousal changes and subjective experience in menstrual cycle is discussed.     

Anxiety sensitivity, the menstrual cycle, and panic disorder: a putative neuroendocrine and psychological interaction

The 2:1 female-to-male sex difference in the prevalence of panic disorder (PD) suggests that there is a sex-specific vulnerability involved in the etiology and/or maintenance of this disorder. The purpose of this paper is to present a new conceptual model, which emphasizes the interaction between a cognitive vulnerability for PD, anxiety sensitivity, and the effects of progesterone and its metabolite, allopregnanolone, on behavioral and physiological responses to stress during the premenstrual phase. This interaction is proposed to be a potential sex-specific pathway that may initiate and/or maintain panic and anxiety symptoms in women. This review paper presents preliminary evidence from both the human and animal literatures to support this new model. Specific topics reviewed include: psychopathology related to the menstrual cycle, anxiety sensitivity and its relationship to the menstrual cycle, PMS, and PMDD, anxiety-modulating effects of progesterone and its neuroactive metabolite, allopregnanolone, and how results from the neuroendocrine literature relate to psychopathology or symptoms associated with the menstrual cycle.     

β-Endorphin withdrawal: a possible cause of premenstrual tension syndrome

The authors propose that premenstrual tension syndrome (PMS) is the result of β-endorphin withdrawal. Sixteen women were included in this study which measured β-endorphin levels on the 7th and 24th day of each woman's menstrual cycle. A significant decline in β-endorphin levels was noted during the progression of the cycle. The severity of symptoms, however, was inversely proportional to the amount of decline in β-endorphin levels. It is hypothesized that the attenuation of endorphin decline may be a compensatory mechanism to moderate the severity of PMS symptoms.     

Women's preferences for sexual dimorphism in height depend on menstrual cycle phase and expected duration of relationship

Human mate preferences are related to many morphological traits, such as female waist-to-hip ratio (WHR), body mass index (BMI), male height or facial symmetry. People also vary in preferences for sexual dimorphism in stature (SDS = male height/female height) between themselves and a potential partner. Here, we demonstrate that women adjust their preference for SDS not only in relation to their own height but also in relation to (1) the phase of menstrual cycle during which their preferences were studied and (2) the sexual strategy (short- versus long-term) they were asked to choose. Taller males (larger SDS) were preferred more often when women were in the follicular (i.e. fertile) phase of their menstrual cycle and when the partners were chosen for short-term relationships. These effects were independent of woman's height. The results show that women in a potentially fertile phase of their menstrual cycle and when choosing a partner who might be less likely to invest in children select genes of taller males.     

Using daily ratings to confirm premenstrual syndrome/late luteal phase dysphoric disorder. Part II. What makes a "real" difference?

Five degree of change criteria used in previous research to confirm premenstrual syndrome/late luteal phase dysphoric disorder (PMS/LLPDD) based on daily ratings were examined to determine how well each differentiated between women claiming to experience severe symptoms and women with normal menstrual experience. Frequency and nature of stressful events and subjective perceptions of impairment were also examined. Ratings were evaluated in 31 women who met DSM III-R criteria for a provisional diagnosis of LLPDD, and 34 women who reported no premenstrual symptomatology. Ratings for a sample of women taking oral contraceptives and a sample of men were also included for comparison purposes. Results indicated no differences between the groups in the frequency of stressful events. However, the PMS/LLPDD group rated their problems as more disturbing and evidenced a cyclical pattern in the occurrence of negative interpersonal interactions at work that was suggestive of some impaired functioning. None of the five change criteria differentiated the PMS/LLPDD group from the normally cycling No PMS group, and only one differentiated this group from the oral contraceptive No PMS group. This was true whether a liberal or conservative standard of confirmation was applied. The implications of these findings for using daily ratings to confirm PMS/LLPDD are discussed.     

Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity and influences learning, memory and cognitive behaviour. The aim of this study is to assess plasma BDNF variations according to hormonal status. METHODS: A total of 60 subjects were included: 20 fertile ovulatory women, 15 amenorrhoeic women and 25 postmenopausal women. Blood samples were collected after overnight fasting. For 5 out of the 20 fertile women, samples were collected every 2 days throughout the whole menstrual cycle. Following basal evaluation, 10 out of 25 postmenopausal women were administered a hormone replacement therapy (HRT) and reevaluated after 6 months of treatment. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. In fertile women, estradiol (E(2)), progesterone and gonadotrophins were also assessed. RESULTS: In fertile women, luteal phase levels of plasma BDNF were significantly higher than follicular phase levels (P < 0.001). BDNF increased from early follicular phase up to Day 14 of the cycle, reaching a pre-ovulatory peak, similar to E(2). A second rise took place during mid-luteal phase, with a peak on Day 24. Amenorrhoeic subjects, as well as postmenopausal women, showed significantly lower plasma BDNF levels compared with fertile females (P < 0.001). BDNF was positively correlated with E(2) and progesterone and negatively correlated with menopausal age. HRT restored BDNF levels to those present in fertile women during the follicular phase. CONCLUSIONS: Plasma BDNF levels are influenced by hormonal status. Modifications in BDNF circulating levels during the menstrual cycle suggest a potential role for gonadal sex hormones (E(2) and progesterone) in regulating neurotrophin expression.     

On the frequency of intercourse around ovulation: evidence for biological influences

BACKGROUND: Intercourse in mammals is often coordinated with ovulation, for example through fluctuations in libido or by the acceleration of ovulation with intercourse. Such coordination has not been established in humans. We explored this possibility by examining patterns of sexual intercourse in relation to ovulation. METHODS: Sixty-eight sexually active North Carolina women with either an intrauterine device or tubal ligation provided data for up to three menstrual cycles. These women collected daily urine specimens and kept daily diaries of intercourse and menstrual bleeding. Major estrogen and progesterone metabolites excreted in urine were used to identify the day of ovulation. The fertile days of the cycle were defined as the 6 consecutive days ending with ovulation. Women contributed a total of 171 ovulatory cycles. Menstrual bleeding days were excluded from analysis. RESULTS: The frequency of intercourse rose during the follicular phase, peaking at ovulation and declining abruptly thereafter. The 6 consecutive days with most frequent intercourse corresponded with the 6 fertile days of the menstrual cycle. Intercourse was 24% more frequent during the 6 fertile days than during the remaining non-bleeding days (P < 0.001). CONCLUSIONS: There apparently are biological factors that promote intercourse during a woman's 6 fertile days.