Diurnal fluctuation of sleep propensity across the menstrual cycle

Most women experience sleep changes across the menstrual cycle. We applied the ultra-short sleep-wake schedule to healthy females to compare their 24-h sleep propensity rhythms in the follicular and luteal phases. The daytime (09.00-16.30 h) subjective sleepiness and the number of slow wave sleep-containing nap trials increased in the luteal phase compared to the follicular phase, but the mean sleep propensity did not change. During the periods of 17.00-00.30 h and 01.00-08.30 h there were no differences between the two phases. These results suggest that increased daytime sleepiness in the luteal phase may be related to brain mechanisms controlling slow wave sleep.     

Self-reported sleep across the menstrual cycle in young, healthy women

OBJECTIVE: To establish the association between subjective sleep and phase of the menstrual cycle in healthy, young, ovulating women. METHODS: Twenty-six women (mean age: 21 years) who did not suffer from any menstrual-associated disorders, and in whom we had detected ovulation, completed daily questionnaires about their sleep over 1 month. RESULTS: The women reported a lower sleep quality over the 3 premenstrual days and 4 days during menstruation, compared to the mid-follicular and early/mid luteal phases. Total sleep time, sleep onset latency, number and duration of awakenings, and morning vigilance were not affected by the menstrual cycle. CONCLUSION: The normal, ovulatory cycle is associated with changes in the perception of sleep quality but not sleep continuity in healthy, young women. The temporal relationship of sleep complaints with menstrual phase should be considered in the evaluation of sleep disorders, particularly insomnia, in women.     

Nocturnal polysomnographic sleep across the menstrual cycle in premenstrual dysphoric disorder

ObjectivesWomen with premenstrual dysphoric disorder (PMDD) experience disturbed mood, altered melatonin circadian rhythms, and frequent reports of insomnia during the luteal phase (LP) of their menstrual cycle. In this study we aimed to investigate nocturnal polysomnographic (PSG) sleep across the menstrual cycle in PMDD women and controls.MethodsSeven PMDD women who indicated insomnia during LP, and five controls, spent every third night throughout a complete menstrual cycle sleeping in the laboratory.ResultsIn PMDD and controls progesterone and core body temperature (BT_core) were elevated during LP compared to the follicular phase (FP). Stage 2 sleep showed a significant main effect of menstrual phase and was significantly increased during mid-LP compared to early-FP in both groups. Rapid eye movement (REM) sleep for both groups was decreased during early-LP compared to early-FP. Slow wave sleep (SWS) was significantly increased, and melatonin significantly decreased, in PMDD women compared to controls.ConclusionsPMDD women who experience insomnia during LP had decreased melatonin secretion and increased SWS compared to controls. The sleep and melatonin findings in PMDD women may be functionally linked. Results also suggest an altered homeostatic regulation of the sleep–wake cycle in PMDD, perhaps implicating melatonin in the homeostatic process of sleep–wake regulation.     

Correlation between the circadian sleep propensity rhythm and hormonal rhythms under ultra-short sleep–wake cycle

The aim of this study was to clarify effects of hormonal and temperature rhythms on circadian fluctuations of sleep propensity. Ten healthy females underwent 24-h sleep deprivation and entered the circadian sleep propensity assessment setting under the ultra-short sleep-wake schedule. During the experiment, sleep propensity rhythm, rectal temperature, and 24-h serum hormone profiles (melatonin, cortisol and thyroid-stimulating hormone) were investigated. The circadian sleep propensity rhythms had two apparent peaks (afternoon and nocturnal peaks) and a trough (nocturnal sleep gate). The timings of the nocturnal sleep gate and the nocturnal peak were correlated exclusively with temperature and melatonin rhythms (P < 0.05), while that of the afternoon peak was significantly correlated with habitual wake time and melatonin rhythm. These results indicate that the circadian sleep propensity rhythm is influenced not only by the circadian pacemaker, but also by sleep habit.     

Hippocampal structural changes across the menstrual cycle

Magnetic resonance imaging (MRI) in association with Jacobian-modulated voxel-based morphometry (VBM) was used to test for regional variation in gray matter over the menstrual cycle. T1-weighted anatomical images were acquired using a spoiled gradient recalled acquisition sequence in 21 women. Each subject was scanned twice: once during the postmenstrual late-follicular phase (Days 10-12 after onset of menses), and once during the premenstrual late-luteal phase (1-5 days before the onset of menses). Gray matter was relatively increased in the right anterior hippocampus and relatively decreased in the right dorsal basal ganglia (globus pallidus/putamen) in the postmenstrual phase. Verbal declarative memory was increased in the postmenstrual vs. premenstrual phase. This first report of human brain structural plasticity associated with the endogenous menstrual cycle extends well-established animal findings of hormone-mediated hippocampal plasticity to humans, and has implications for understanding alterations in cognition and behavior across the menstrual cycle.     

Circadian rhythms, sleep, and the menstrual cycle

Women with ovulatory menstrual cycles have a circadian rhythm superimposed on the menstrual-associated rhythm; in turn, menstrual events affect the circadian rhythm. In this paper, we review circadian rhythms in temperature, selected hormone profiles, and sleep-wake behavior in healthy women at different phases of the menstrual cycle. The effects on menstrual cycle rhythmicity of disrupted circadian rhythms, for example, with shiftwork and altered circadian rhythms in women with menstrual-related mood disturbances, are discussed. Compared to the follicular phase, in the post-ovulation luteal phase, body temperature is elevated, but the amplitude of the temperature rhythm is reduced. Evidence indicates that the amplitude of other rhythms, such as melatonin and cortisol, may also be blunted in the luteal phase. Subjective sleep quality is lowest around menses, but the timing and composition of sleep remains relatively stable across the menstrual cycle in healthy women, apart from an increase in spindle frequency activity and a minor decrease in rapid eye movement (REM) sleep during the luteal phase. Disruption of circadian rhythms is associated with disturbances in menstrual function. Female shiftworkers compared to non-shiftworkers are more likely to report menstrual irregularity and longer menstrual cycles. There also is accumulating evidence that circadian disruption increases the risk of breast cancer in women, possibly due to altered light exposure and reduced melatonin secretion. Further investigations into the biological consequences of circadian disruption in women will offer insight into some menstrual-associated disorders, including mood changes, as well as reproductive function and possible links with breast cancer.     

Transcallosal inhibition across the menstrual cycle: a TMS study.

OBJECTIVE: To determine if there are steroid-dependent changes in transcallosal transfer during the menstrual cycle in normal women. METHODS: We tested 13 normally cycling women during the menstrual, follicular and midluteal phases. Blood levels of estradiol (E) and progesterone (P) were determined by radioimmunoassay. Ipsilateral tonic voluntary muscle activity suppression, called ipsilateral silent period (iSP), was evoked by applying transcranial magnetic stimulation (TMS) over the left motor cortex and by measuring the EMG of the ipsilateral first dorsal interosseus (FDI) muscle. Both iSP-duration and transcallosal conduction times were measured and related to cycle phase and steroid levels. RESULTS: Duration of iSPs varied over the cycle with largest differences between follicular and midluteal phases. During the midluteal phase high levels of P were significantly related to short iSPs. This relation also applied to E levels and iSPs during the follicular phase. CONCLUSIONS: Our study shows for the first time that the transcallosal transfer is modulated by E and P and changes over the menstrual cycle. SIGNIFICANCE: It is suggested that gonadal steroid hormones affect the interhemispheric interaction and change the functional cerebral organization sex dependently via its neuromodulatory properties on GABAergic and glutamatergic neurons.     

Variations in memory function and sex steroid hormones across the menstrual cycle.

Memory, mood, and hormone levels were measured in 25 women during the menstrual and luteal phases of their cycles. Significantly lower visual memory (delayed recall) scores were found during the menstrual phase compared to the luteal phase. No phase differences were found on mood measures or on other memory measures including digit span, paired-associate learning, immediate recall of visual material, and immediate or delayed paragraph recall. The visual memory decrease was most prominent in approximately one-half of the sample and was significantly correlated with plasma progesterone in the luteal phase. For all subjects, paragraph recall scores were negatively correlated with free testosterone levels, whereas paired-associate learning was positively correlated with estradiol levels in the luteal phase. These results suggest that changes in memory test performance may be associated with sex steroid levels, particularly in some subgroups of women.     

Hemispheric asymmetry in spatial attention across the menstrual cycle

Functional cerebral asymmetries (FCAs) are known to fluctuate across the menstrual cycle. The mechanisms of these sex hormonal modulations are poorly understood. It has been suggested that gonadal steroid hormones might suppress or specifically activate one hemisphere. However, recent studies suggest that high levels of gonadal steroid hormones reduce FCAs by its modulating effects on cortico-cortical transmission. To investigate the activating effects of gonadal steroid hormones on the interhemispheric interaction, a visual line-bisection task was administered to normally cycling women during menses and the midluteal cycle phase as well as to similar-aged healthy men. The results replicate previous findings of a sex difference in line-bisection as a function of hand-use and show that the hand-use effect fluctuates across the menstrual cycle. High levels of estradiol during the midluteal phase were related to a decrease of the hand-use effect. It is concluded that cycle-related fluctuations in levels of gonadal steroid hormones affect hemispheric asymmetry of spatial attention, presumably by interhemispheric spreading of neuronal activation.     

Mood across the menstrual cycle and number of menstrual symptoms reported: a cross-sectional study

This study assessed mood among 110 women at three phases of the menstrual cycle and its relationship with the number of reported menstrual symptoms. Women who reported fewer menstrually-related symptoms tended to have generally higher mood scores, but specific depression of mood during menses was found among the subgroup of women who reported fewer menstrual symptoms. Contraceptive pill usage was not related to mood variation across the menstrual cycle. The findings raise questions about the validity of self-reports of menstrually-related symptoms.     

Objective sleep interruption and reproductive hormone dynamics in the menstrual cycle

ObjectivesWomen report greater sleep disturbance during the premenstrual phase of the menstrual cycle and during menses. However, the putative hormonal basis of perceived menstrual cycle-related sleep disturbance has not been investigated directly. We examined associations of objective measures of sleep fragmentation with reproductive hormone levels in healthy, premenopausal women.MethodsTwenty-seven women with monthly menses had hormone levels measured at two time points during a single menstrual cycle: the follicular phase and the peri-ovulatory to mid-luteal phase. A single night of home polysomnography (PSG) was recorded on the day of the peri-ovulatory/mid-luteal-phase blood draw. Serum progesterone, estradiol, and estrone levels concurrent with PSG and rate of change in progesterone (PROGslope) from the follicular blood draw to PSG were correlated with log-transformed wake after sleep onset (lnWASO%) and number of wakes/hour of sleep (lnWake-Index) using linear regression.ResultsSleep was more fragmented in association with a steeper PROGslope (lnWASO% p = 0.016; lnWake-Index p = 0.08) and higher concurrent estrone level (lnWASO% p = 0.03; lnWake-Index p = 0.01), but the effect of estrone on WASO was lost after accounting for PROGslope. WASO% and Wake-Index were not associated with concomitant progesterone or estradiol levels.ConclusionsA steeper rate of rise in progesterone levels from the follicular phase through the mid-luteal phase was associated with significantly greater WASO, establishing a link between reproductive hormone dynamics and sleep fragmentation in the luteal phase of the menstrual cycle.     

Distribution of seizures across the menstrual cycle in women with epilepsy

The purpose of this study was to determine whether seizure frequency and cycle days with seizure occurrence vary across the menstrual cycle. The subjects were the first 100 women with intractable focal onset seizures, 13–45 years old, who completed the baseline phase of the National Institutes of Health (NIH) Progesterone Trial. Each subject recorded seizures and menses during a 3‐month baseline phase. Data consisted of (1) seizure numbers for each cycle day and (2) cycle days with seizure occurrence. Statistical comparisons of seizure frequency and days with seizures were performed using generalized estimating equation one‐way analysis of variance (ANOVA) and logistic regression followed by pairwise multiple comparisons of days based on the least square means. Seizure numbers and cycle days with seizure occurrence varied across the menstrual cycle. There was an approximately twofold difference between the highest (day 1) and lowest (day ?8) values for both seizure frequency and days with occurrence. The demonstration of variation in seizure frequency and cycle days with seizure occurrence across the menstrual cycle, as well as identification of specific days that have substantially higher or lower frequencies than other days, supports the existence of catamenial epilepsy.     

Implicit memory varies across the menstrual cycle: estrogen effects in young women.

Evidence that ovarian steroid hormones such as estrogen and progesterone affect cognition comes from studies of memory in older women receiving estrogen replacement therapy and studies of sexually dimorphic skills in young women across the menstrual cycle. Sixteen women (ages 18-28) completed tests of memory (implicit category exemplar generation, category-cued recall, implicit fragmented object identification) and sexually dimorphic skills (fine motor coordination, verbal fluency, mental rotations) at the early follicular (low estrogen and progesterone) and midluteal (high estrogen and progesterone) phases of the menstrual cycle. Performance on category exemplar generation, a test of conceptual implicit memory, was better at the midluteal than the follicular phase. In contrast, performance on a test of explicit memory, category-cued recall, did not vary across the menstrual cycle. At Session 1, women in the follicular phase performed better on the fragmented object identification task than did those in the midluteal phase. This unexpected finding suggests that high levels of ovarian hormones might inhibit perceptual object priming. Results confirmed previous reports of decreased mental rotations and improved motor skills and fluency in the midluteal phase. Estradiol levels correlated positively with verbal fluency and negatively with mental rotations and perceptual priming, which suggest that estrogen, and not progesterone, was responsible for the observed changes in cognition. Mood did not vary across the cycle phases. Overall, the findings suggest that estrogen may facilitate the automatic activation of verbal representations in memory.     

Verbal and spatial functions across the menstrual cycle in healthy young women

The effects of the menstrual cycle on cognitive functions were investigated using simple verbal and spatial tasks. Eight healthy young women with a regular, established 28-day menstrual cycle and the occurrence of ovulation on day 14 were tested four times during one cycle. Ten women on non-tricyclic birth control pills were also tested weekly during one cycle. Both groups were matched in age, handedness and education. No significant difference in spatial ability was found but improved verbal working memory, as measured by the verbal span score, was associated with periods of high estrogen levels.     

Peak visual gamma frequency is modified across the healthy menstrual cycle

Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABA_A receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females’ mid‐luteal phase when progesterone and estradiol are highest, and early follicular phase when progesterone and estradiol are lowest. Significantly higher (～5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modeling, these changes were linked to stronger self‐inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition, the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma‐band oscillations.     

Sex and modulatory menstrual cycle effects on sleep related memory consolidation

The benefit of sleep in general for memory consolidation is well known. The relevance of sleep characteristics and the influence of hormones are not well studied. We explored the effects of a nap on memory consolidation of motor (finger-tapping-task) and verbal (associated-word-pairs) tasks in following settings: A: young, healthy males and females during early-follicular phase (n=40) and B: females during mid-luteal and early-follicular phase in the menstrual cycle (n=15). We found a sex and in women a menstrual cycle effect on memory performance following a nap. Men performed significantly better after a nap and women did so only in the mid-luteal phase of their menstrual cycle. Only the men and the women in their mid-luteal phase experienced a significant increase in spindle activity after learning. Furthermore, in women estrogen correlated significantly with the offline change in declarative learning and progesterone with motor learning. The ratio of the 2nd and 4th digit, which has been associated to fetal sex hormones and cognitive sex differences, significantly predicted the average performance of the female subjects in the learning tasks. Our results demonstrate that sleep-related memory consolidation has a higher complexity and more influencing factors than previously assumed. There is a sex and menstrual cycle effect, which seems to be mediated by female hormones and sleep spindles. Further, contrary to previous reports, consolidation of a simple motor task can be induced by a 45 min NREM sleep nap, thus not dependent on REM sleep.