Menstrual cycle and premenstrual syndrome: Modifiers of cardiovascular reactivity in women.

15 women prospectively diagnosed with premenstrual syndrome (PMS) and 15 non-PMS women were each tested twice for cardiovascular stress reactivity and behavioral performance, once during the follicular phase and once during the luteal phase of their cycle. Although blood pressure and heart rate responses to stress did not differ across the menstrual cycle in either group of women, for the non-PMS women, differences in hemodynamic responses were observed across the 2 phases. The luteal phase was associated with greater stroke volume responses and lesser vascular tone. For the PMS women, none of their cardiovascular measures differed across their cycle. Instead, these women showed significantly attenuated blood pressure and heart rate responses compared with non-PMS women, irrespective of cycle phase. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mood and performance changes in women with premenstrual dysphoric disorder: acute effects of alprazolam

This study determined if women with premenstrual dysphoric disorder (PMS) showed impaired mood and performance when they were experiencing their premenstrual symptoms, and if the effects of alprazolam varied as a function of menstrual cycle phase. Under double-blind conditions, the acute effects of placebo and alprazolam (0.25, 0.50, 0.75 mg) were tested during both luteal and follicular phases. Women with confirmed PMS experienced substantial changes in mood as a function of menstrual cycle phase. However, under controlled laboratory conditions, acute doses of alprazolam did not improve negative premenstrual mood, but rather increased negative mood in the follicular phase. Alprazolam impaired task performance, although this impairment was generally similar in both phases when baseline phase differences were taken into consideration. Consistent with the failure of alprazolam to improve mood premenstrually, subjective measures indicative of abuse liability were not increased following alprazolam. Taken together, these data suggest that acute administration of alprazolam doses are not clinically useful for the treatment of PMS.     

A comparison of the psychological and hormonal factors in women with and without premenstrual syndrome.

Women with premenstrual syndrome (PMS; n?=?14) were compared with women without premenstrual syndrome (n?=?14). The diagnosis was based on the volunteers' responses to the Premenstrual Assessment Form, their medical history, a physical examination, and the Utah PMS Calendar. After assignment to the non-PMS or PMS group, each subject was studied for one menstrual cycle and was evaluated, once during the follicular phase and twice during the luteal phase. On each of these occasions, circulating concentrations of estradiol and progesterone were determined, and the Depression Adjective Checklist (DACL), the Minnesota Multiphase Personality Inventory (MMPI), and the Attributional Style Questionnaire were completed. Each subject recorded daily her physical symptoms on the Utah PMS Calendar. During the luteal phase, women with PMS had significantly higher levels of depression as measured by the DACL and MMPI than women without PMS. The two groups did not differ in the follicular phase. These findings suggest a luteal phase disorder superimposed on a background free of psychiatric or physiological illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estimated number of patients with chronic renal failure but not with end-stage renal disease in Japan: comparisons between two estimation methods

BACKGROUND: A significant number of American women of childbearing age are troubled by premenstrual symptoms, but the underlying cause is not understood, resulting in inadequate therapy. OBJECTIVES: To use basal levels of cortisol to differentiate women with low symptom (LS) patterns of turmoil-type premenstrual symptoms from women with premenstrual symptom (PMS) patterns and from women with premenstrual magnification (PMM) patterns of turmoil-type premenstrual symptoms. METHOD: Symptom and cortisol patterns of women were monitored for three consecutive menstrual cycles. Three distinct groups of women were identified based on symptom patterns and types. RESULTS: Significant differences in symptom severity among groups were observed during the follicular (F = 203; df= 2, 24; p < .0001) and luteal phases (F= 51.3; df= 2, 24; p< .0001) of the cycle. There were no statistically significant differences in cortisol among groups for the follicular phase, but there were during the luteal phase (F= 4.0; df= 2, 24; p= .03). CONCLUSIONS: Altered regulation of the stress axis may be involved in mediating turmoil-type PMS.     

Patients with premenstrual syndrome have decreased saccadic eye velocity compared to control subjects

BACKGROUND: Prior neurophysiological studies on patients with premenstrual syndrome (PMS) have revealed sleep electroencephalographic alterations in both cycle phases. We report on a study evaluating saccadic eye movements in PMS patients. METHODS: Saccadic eye movements were examined in 21 women with and 21 women without PMS on two occasions in the midfollicular and late luteal phase, respectively. On each occasion, plasma levels for estradiol, progesterone, and neuroactive progesterone metabolites were determined. RESULTS: PMS patients had decreased saccadic eye velocity (SEV) compared to control subjects. This finding was most evident in the luteal phase, whereas the difference between groups approached significance in the follicular phase. Saccade accuracy and saccade latency were not different between the two groups. Control subjects increased their SEV in the luteal phase compared to the follicular phase, whereas PMS patients did not. PMS patients rated themselves more sedated than control subjects on the testing days in both phases of the menstrual cycle. Plasma levels of gonadal hormones and neuroactive steroids did not differ between the study groups. CONCLUSIONS: The findings of a decreased SEV in PMS patients could be due to poor sleep and consequently increased sedation, but might also indicate that gamma-aminobutyric acidergic inhibition is different in patients with premenstrual syndrome.     

Patients with premenstrual syndrome have a different sensitivity to a neuroactive steroid during the menstrual cycle compared to control subjects

We have evaluated the functional sensitivity to a neuroactive steroid in 12 women with and 12 women without premenstrual syndrome (PMS) at two stages of the menstrual cycle, by comparing the effects of three increasing doses of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye velocity (SEV) and self-rated sedation. Control subjects in the follicular and luteal phase showed a significant reduction in SEV after pregnanolone injections compared to vehicle. In PMS patients, pregnanolone injections induced a significant dose-related decrease in SEV compared to vehicle only in the follicular phase, not in the luteal phase. After pregnanolone injections, sedation scores increased significantly from vehicle among control subjects in the luteal phase but not among PMS patients in either cycle phase. High-severity PMS patients responded with less decrease in SEV and less increase in sedation scores following pregnanolone injections compared to low-severity patients. Control subjects increased their SEV response to pregnanolone in the luteal phase compared to the follicular phase, whereas PMS patients did not. These findings are compatible with a decreased GABAA-receptor sensitivity in brain areas controlling saccadic eye movements among PMS patients in the late luteal phase.     

Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one

The relationship between symptoms of premenstrual syndrome (PMS) and serum levels of pregnenolone (Pe), pregnenolone sulfate (PS), 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha- pregnan-20-one (5 alpha-THP), LH, 17 beta-estradiol (E2), and progesterone (P) was investigated during 2 consecutive menstrual cycles in 12 patients using daily measurements. Corresponding hormones were also measured during 1 cycle in 8 control women. Pe, PS, 5 alpha-DHP, and 5 alpha-THP showed a significant cyclicity within menstrual cycles and a high rate of correlation with P variation in both PMS patients and controls. No significant difference was found between PMS patients and controls in average serum concentrations of Pe, PS, 5 alpha-DHP, 5 alpha-THP, and LH during the luteal phase, whereas a significantly higher level of E2 and a lower level of P were observed in PMS patients. The variation in symptom scores was compared with that in hormone levels within each woman. The symptom peak showed a delay of 3-4 days after the serum P, Pe, 5 alpha-DHP, and 5 alpha-THP peaks. However, the plasma PS peak appeared on the same day or only 1 day before the symptom peak in PMS patients. When comparing the 2 cycles studied, more negative symptoms occurred in cycles with higher luteal phase E2, Pe, and PS concentrations, whereas higher luteal phase 5 alpha-DHP and 5 alpha-THP concentrations were associated with improved symptom ratings in PMS patients. These results suggest that the mentioned steroids are related to the severity of distressing symptoms in PMS patients.     

Ischemic but not thermal pain sensitivity varies across the menstrual cycle

OBJECTIVE AND METHOD: Findings from both animal and human research suggest that pain sensitivity changes across the menstrual cycle; however, among humans the nature of these menstrual cycle effects remains unclear. The present study used a repeated-measures design to evaluate changes in thermal and ischemic pain responses during three phases of the menstrual cycle, midfollicular (postmenstrual), ovulatory, and mid-to-late luteal (premenstrual), in 11 healthy women. The cycle phase during which subjects began their participation was determined randomly. Plasma levels of estrogen, progesterone, luteinizing hormone (LH), testosterone, and beta-endorphin were determined at each experimental session. Participants also completed a daily diary of physical and emotional symptoms for two complete menstrual cycles before the experimental sessions. RESULTS: The results indicated that women showed less ischemic pain sensitivity during the midfollicular compared with the ovulatory and mid-to-late luteal phases, but thermal pain responses did not vary significantly across menstrual cycle phases. Physical and emotional symptoms were minimal and did not change significantly across the menstrual cycle. CONCLUSIONS: These findings indicate greater ischemic but not thermal pain sensitivity among women after the midcycle LH surge. The practical relevance and potential mechanisms of these findings are discussed.     

Adrenergic receptors in premenstrual dysphoric disorder: I. Platelet alpha 2 receptors: Gi protein coupling, phase of menstrual cycle, and prediction of luteal phase symptom severity

BACKGROUND: Abnormal alpha 2-adrenergic receptor (AR) function is implicated in anxiety and depressive disorders. Premenstrual dysphoric disorder (PMDD) is characterized by anxiety and depressive symptoms, which may be associated with changes in alpha 2AR function. Previous studies on alpha 2AR function during phases of the menstrual cycle in controls and PMDD patients are inconsistent. METHODS: alpha 2AR function was examined in 16 PMDD patients and 15 controls during the follicular phase, and in 10 PMDD patients during late luteal phase. Antagonist-measured maximum binding capacity, agonist-measured receptor density in high- and low-conformational states, and agonist affinity to both states were measured. Coupling efficiency to Gi protein was estimated. RESULTS: There were no significant differences in coupling efficiency. PMDD patients had significantly low antagonist affinity; there were no differences in other binding parameters. There were no changes in alpha 2AR binding parameters between phases of menstrual cycle in PMDD women. alpha 2AR density and symptom severity were inversely related during the follicular phase in controls and patients. During luteal phase, alpha 2AR density correlated positively with symptom severity in patients. High follicular alpha 2AR density predicted more severe luteal symptoms in PMDD patients. CONCLUSIONS: These findings are discussed in view of the molecular biology of alpha 2AR, and their role in PMDD, anxiety, and depressive disorders.     

Reduction in urinary prostaglandin excretion in the premenstrual syndrome

The purpose of the present work was to study some factors involved in renal handling of salt and water in the premenstrual syndrome (PMS), in which salt and water retention is frequently observed. In 18 women with PMS and in 18 healthy women we studied the levels of cyclic adenosine monophosphate, aldosterone, prostaglandin E2, prostaglandin F2 alpha and kallikrein in urinary samples collected during the luteal phase. There was no difference between the two groups regarding sodium, aldosterone and kallikrein urinary excretion. In the PMS group there was a significant reduction in urinary excretion of cyclic adenosine monophosphate, prostaglandin E2 and prostaglandin F2 alpha with respect to the control group. At multivariate analysis sodium urinary excretion proved not to be the same as the model validated in healthy women. There may be different renal handling of water and electrolytes during the luteal phase of the menstrual cycle in women with PMS.     

Menstrual cycle, beta-endorphins, and pain sensitivity in premenstrual dysphoric disorder.

This study examined pain sensitivity and pain modularity mechanisms (e.g., beta-endorphin levels, blood pressure) in women with premenstrual dysphoric disorder (PMDD; n=27) and healthy controls (n=27) during the follicular and luteal phases of the menstrual cycle. Physiological measures were taken during rest and ischemic pain testing. In both cycle phases, PMDD women (a) displayed lower resting cortisol and beta-endorphin levels and (b) exhibited shorter pain threshold and tolerance times and greater pain unpleasantness ratings during pain. PMDD women also reported greater pain unpleasantness and intensity and had lower beta-endorphin levels in their luteal phase and tended to display higher blood pressure levels at rest and during pain testing. Results suggest that endogenous opioids may be pathophysiologically relevant to PMDD and that the hypothalamic-pituitary-gonadal axis may modulate pain sensitivity in PMDD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Premenstrual syndrome: diagnosis and intervention

Premenstrual syndrome (PMS) is a recurrent disorder that occurs in the luteal phase of the menstrual cycle. It is characterized by intense physical, psychologic, and behavioral changes that interrupt interpersonal relationships and disrupt the lives of affected women. Up to 40% of women of childbearing age have some form of PMS, and up to 10% have severe signs and symptoms. There are at least four types of PMS, each with its own constellation of signs and symptoms. Related illnesses or illnesses that need to be ruled out include diabetes mellitus, thyroid dysfunction, hypoglycemia, and primary and secondary dysmenorrhea. Difficulty in identifying the exact etiology of the disorder is documented. Diagnostic issues include confusion over exact signs and symptoms, differential diagnoses, pertinent laboratory data, careful history taking, and the importance of women recording a menstrual cycle history on a calendar. Recommended first-line treatments include a diet low in salt, fat, caffeine, and sugar; an aerobic exercise regimen; and stress reduction via changes in lifestyle.     

Hormonal and metabolic responses to exercise across time of day and menstrual cycle phase

Two studies, each utilizing short-term treadmill exercise of a different intensity, assessed the metabolic and hormonal responses of women to exercise in the morning (AM) and late afternoon (PM). In study 1, plasma concentrations of growth hormone, arginine vasopressin, catecholamines, adrenocorticotropic hormone, cortisol, lactate, and glucose were measured before, during, and after high-intensity exercise (90% maximal O2 uptake) in the AM and PM. In study 2, plasma concentrations of adrenocorticotropic hormone, cortisol, lactate, and glucose were measured before, during, and after moderate-intensity exercise (70% maximal O2 uptake) in the AM and PM in the follicular (days 3-9), midcycle (days 10-16), and luteal (days 18-26) phases of the menstrual cycle. The results of studies 1 and 2 revealed no significant diurnal differences in the magnitude of responses for any measured variable. In addition, study 2 revealed a significant time-by-phase interaction for glucose (P = 0. 014). However, net integrated responses were similar across cycle phases. These data suggest that metabolic and hormonal responses to short-term, high-intensity exercise can be assessed with equal reliability in the AM and PM and that there are subtle differences in blood glucose responses to moderate-intensity exercise across menstrual cycle phase.     

Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.     

Loss of normal cyclical beta 2 adrenoceptor regulation and increased premenstrual responsiveness to adenosine monophosphate in stable female asthmatic patients

BACKGROUND: A study was undertaken to investigate the influence of the menstrual cycle on airway responsiveness and beta 2 adrenoceptor function in female asthmatic patients. It has previously been shown that normal women exhibit cyclical changes in beta 2 adrenoceptor function with an increase in beta 2 adrenoceptor density in the luteal phase during the premenstrual period. METHODS: Fifteen women with stable, well controlled asthma (mean forced expiratory volume in one second (FEV1) 2.971 (93.8% predicted)) were evaluated. Measurements were made at the follicular phase (days 1-6) and the luteal phase (days 21-24) of the menstrual cycle. Airway responsiveness was assessed using adenosine 5'-monophosphate (AMP) and expressed as PC20 AMP. Beta 2 adrenoceptor function was evaluated by measuring lymphocyte beta 2 adrenoceptor parameters and constructing dose-response curves to salbutamol (100-1600 micrograms). The levels of female sex hormones were also measured at both phases of the cycle. RESULTS: There were significant increases in serum levels of both oestradiol (2.2-fold, p < 0.001) and progesterone (7.2-fold, p < 0.05) between the follicular and luteal phases. Geometric mean PC20 AMP was 19.0 mg/ml and 7.6 mg/ml during the follicular and luteal phases, respectively (p < 0.05), a 2.51-fold difference (95% CI 1.19 to 5.30) amounting to 1.33 doubling doses of AMP. There was no change in lymphocyte beta 2 adrenoceptor parameters or in airway beta 2 adrenoceptor responses to salbutamol between the two phases. CONCLUSIONS: Despite an appropriate rise in female sex hormones during the luteal period, beta 2 adrenoceptor regulation in female asthmatic subjects shows a loss of the normal cyclical pattern. In addition, there were cyclical changes in airway responsiveness to AMP which was highest during the premenstrual period. Thus, drugs such as theophylline which block adenosine receptors warrant investigation in premenstrual asthma.     

Vascular endothelial growth factor in premenopausal women--indicator of the best time for breast cancer surgery?

Timing of surgery in premenopausal patients with breast cancer remains controversial. Angiogenesis is essential for tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. We aimed to determine whether the study of VEGF in relation to the menstrual cycle could help further the understanding of this issue of surgical intervention. Fourteen premenopausal women were recruited, along with three post-menopausal women, a woman on an oral contraceptive pill and a single male subject. Between eight and 11 samples were taken per person, over one menstrual cycle (over 1 month in the five controls) and analysed for sex hormones and VEGF165. Serum VEGF was significantly lower in the luteal phase and showed a significant negative correlation with progesterone in all 14 premenopausal women. No inter-sample variations of VEGF were noted in the controls. Serum from both phases of the cycle from one subject was added to MCF-7 breast cancer cells; VEGF expression in the supernatant was lower in the cells to which the luteal phase serum was added. The lowering of a potent angiogenic cytokine in the luteal phase suggests a possible decreased potential for micrometastasis establishment in that phase. This fall in VEGF may be an effect of progesterone and should be the focus of future studies.     

Thermic effect of food during each phase of the menstrual cycle

The effect of the menstrual cycle on the thermic effect of food (TEF) was examined in eight healthy, normal-weight [mean +/- SD: 56.1 +/- 5.6 kg and body mass index (in kg/m2) 21.3 +/- 1.8] women aged 22-38 y. Their lean body mass and fat mass were 39.4 +/- 2.7 kg and 16.9 +/- 6.5 kg, respectively. TEF was measured on 4 separate days selected to match the four phases of a menstrual cycle: early follicular, follicular, luteal, and late luteal. The volunteers consumed a 3138-kJ liquid meal (54.5% carbohydrate, 14.0% protein, and 31.5% fat) on each test day. Resting metabolic rate was measured for 55 min before the meal and every 30 min after the start of the meal for 205 min. Although resting metabolic rate remained unchanged, there was a significant difference (P < 0.01 by ANOVA) in mean (+/- SEM) values for TEF among the four phases of the cycle: 0.94 +/- 0.05 kJ/min during the early follicular phase, 0.86 +/- 0.09 kJ/min during the follicular phase, 0.70 +/- 0.10 kJ/min during the luteal phase, and 0.76 +/- 0.07 kJ/min during the late luteal phase. TEF decreased significantly (P < 0.025 by paired t test) during postovulation (average of luteal and late luteal phases), when it was 0.73 +/- 0.07 kJ/min, compared with preovulation (average of early follicular and follicular phases), when it was 0.90 +/- 0.06 kJ/min. In conclusion, TEF decreased during the luteal phase of the menstrual cycle, possibly as a result of impairment of glucose uptake and slower transit of food through the upper gastrointestinal tract.     

Sadie wouldn''t let go of her pain

Plasma concentration of metallic ions levels during menstrual cycle of twenty normally menstruating women were observed in four phases i.e. menses, follicular, ovulatory and luteal. The concentration of magnesium, zinc, selenium and manganese was highest during menses and lowest at ovulatory phase. There was rise in ionic levels of magnesium and selenium, while fall in zinc and manganese during luteal phase. Findings demonstrate changes in metallic ions (Magnesium, zinc, selenium and manganese) level in relation to hormonal status during menstrual cycle in women.     

Baby Friendly Hospital Initiative: the Kerala experience

OBJECTIVE: Our purpose was to determine whether color flow pulsed Doppler could predict a luteal phase defect (LDP). METHOD: Twenty-one women with regular menstrual cycles and at risk for luteal phase defect were examined by transvaginal color Doppler during the follicular and luteal phase of the menstrual cycle. Progesterone was measured on the day of the Doppler exam. Ovulation was determined from the lutenizing hormone (LH) surge. Endometrial biopsy during the late luteal phase was performed on each patient. RESULT: Six patients (28.5%) were diagnosed with luteal phase defect. Mean resistance index in patients with luteal phase defect was significantly higher only throughout the luteal phases (p = 0.02). Mean progesterone levels were significantly lower for patients with LPD than for normal women (p < 0.001). Mean pulsatility index in luteal phase deficient cycles was significantly higher throughout the follicular and luteal phases (p = 0.03). CONCLUSION: Color Doppler may aid in assessing luteal phase adequacy. Doppler indices of corpus luteum blood flow in combination to plasma progesterone may be a useful index of luteal function.     

Does corpus luteum locally affect follicular growth negatively?

In this study bilateral ovarian follicular growth during the luteal phase was investigated in relation to the ovary where ovulation occurred. The diameter of the largest follicle in the contralateral ovary without corpus luteum and in the ipsilateral ovary with corpus luteum was measured using vaginosonography in a total of 66 natural cycles of 27 normally cycling women undergoing treatment with intrauterine insemination (IUI). None of the women received ovarian stimulation or luteal support. Follicles from 2 to 11 mm in diameter were measured in early luteal phase (day +1 to +4), mid-luteal phase (day +5 to +9) and late luteal phase (day +10 onwards). The mean diameters of the largest follicle in the contralateral ovary without corpus luteum during the early, mid- and late luteal phases were 6.81 +/- 1.33 (mean +/- SD), 6.14 +/- 1.29 and 5.71 +/- 1.17 mm respectively, while those of the ipsilateral ovary with corpus luteum were 6.48 +/- 1.40, 5.65 +/- 1.47 and 4.98 +/- 1.19 mm respectively. While there was no significant difference during the early luteal phase, the mean diameter of the largest follicle in the ipsilateral ovary with corpus luteum was significantly smaller than that of the contralateral ovary without corpus luteum during the mid-luteal phase (P < 0.004) and the late luteal phase (P < 0.0005). These results indicate that the corpus luteum locally affects neighbouring follicular growth negatively during the luteal phase of the menstrual cycle, with the most pronounced effect expressed in the mid- and late luteal phases.