Mood, sexuality, oral contraceptives and the menstrual cycle

4112 women completed a retrospective questionnaire indicating when during their last menstrual cycle they felt their well-being and sexual interest to be at their best and worst. The commonest pattern was for well-being to be lowest during the premenstrual and highest during the postmenstrual week. Sexual interest was strongly associated with well-being, suggesting that variations of well-being have a powerful effect on sexuality in the majority of women. Oral contraceptive users, though broadly similar in their reported pattern, were less likely to show peaks and troughs of well-being and highs and lows of sexual interest. This was most evident in the subgroup of monophasic pill users who showed the least tendency to variations in both well-being and sexual interest, and a greater tendency to show either peaks or troughs of well-being during menstruation. Triphasic pill users were intermediate between monophasic and non-pill users.     

Hormonal contraceptives,menstrual cycle and brain response to faces

Both behavioral and neuroimaging evidence support a female advantage in the perception of human faces. Here we explored the possibility that this relationship may be partially mediated by female sex hormones by investigating the relationship between the brain’s response to faces and the use of oral contraceptives, as well as the phase of the menstrual cycle. First, functional magnetic resonance images were acquired in 20 young women [10 freely cycling and 10 taking oral contraception (OC)] during two phases of their cycle: mid-cycle and menstruation. We found stronger neural responses to faces in the right fusiform face area (FFA) in women taking oral contraceptives (vs freely cycling women) and during mid-cycle (vs menstruation) in both groups. Mean blood oxygenation level-dependent response in both left and right FFA increased as function of the duration of OC use. Next, this relationship between the use of OC and FFA response was replicated in an independent sample of 110 adolescent girls. Finally in a parallel behavioral study carried out in another sample of women, we found no evidence of differences in the pattern of eye movements while viewing faces between freely cycling women vs those taking oral contraceptives. The imaging findings might indicate enhanced processing of social cues in women taking OC and women during mid-cycle.     

Influence of 17-beta-estradiol on cerebrovascular impedance during menstrual cycle in women

Numerous experimental studies showed that estrogen alters diameters of cerebral arteries by modifying production of vasoactive substances. In this study, we address a question whether increased concentration of 17-beta-estradiol (E2) during a typical menstrual cycle of young, healthy women influences cerebrovascular impedance, as measured with Doppler pulsatility index (PI) in the common (CCA), internal (ICA), and external (ECA) carotid arteries using duplex Doppler sonography. PI was determined and correlated with plasma E2 concentration in 14 women (ages 23-25) throughout their menstrual cycle. The concentration of E2 increased in the follicular phase of the cycle and reached a peak of 140-300 pg/ml on days 13 and 14, whereas concentration of progesterone remained low (<1 ng/ml). Along with an increase in E2 concentration, the ICA PI decreased from its initial level on average by 11% on day 13 and by 7% on day 14 (r=-0.41, P<0.05). In contrast, the value of the ECA PI showed an increasing trend during the peak of E2 concentration. There were no significant changes in the CCA PI as well as in the systolic blood pressure, heart rate, hematocrit, and hemoglobin concentration during the menstrual cycle. Cerebral vascular impedance in young women is modulated by concentration of E2 throughout the menstrual cycle. The decrease in the ICA PI during the late follicular phase seems to be attributed to a decrease in cerebrovascular resistance.     

Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone-containing oral contraceptives

Introduction

Oral contraceptives (OC) increase the risk of venous thromboembolism that depends on the OC formulation and could at least partially be explained by impaired function of the protein C-system (APC resistance) and the tissue factor pathway inhibitor (TFPI)-system. There is limited information available on the effects of OC, containing a newer progestogen- drospirenone (DRSP-OC) on these two major anticoagulant pathways, thrombin generation, reflecting the overall state of coagulation, and other coagulation parameters.

Methods

In a study population consisting of 14 healthy women (age 21–33 years) we investigated the effect of the menstrual cycle and subsequent use of DRSP-OC on APC resistance, the function of the TFPI-system, thrombin generation and on their major determinants, i.e. prothrombin, antithrombin, FV, FX, FVIII, protein C, protein S_{(total and free)} and TFPI_{(full-length and free)}.

Results

All studied parameters remained unchanged during the menstrual cycle. During DRSP-OC use we observed a significant increase in APC resistance (~ 2.4-fold), thrombin generation measured at low (~ 2.2-fold) and high tissue factor concentrations (~ 1.4-fold), plasma concentrations of prothrombin (19%), FX (31%), FVIII (17%) and protein C (43%). DRSP-OC use impaired the function of the TFPI-system and decreased plasma levels of antithrombin (− 6%), FV (− 22%), protein S_total (− 21%), protein S_free (− 20%), TFPI_full-length (− 36%) and TFPI_free (− 46%).

Conclusions

DRSP-OC caused procoagulant changes in all studied haemostatic parameters. The impairment of the protein C- and TFPI-systems was more pronounced than the impairment of the coagulation pathways and can at least partially account for the increased risk of venous thromboembolism in users of DRSP-OC.     

Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation.

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.     

Changes in physiological,eeg and psychological parameters in women during the spontaneous menstrual cycle and following oral contraceptives

In a controlled cross-over design study performed with 14 female subjects, serum hormone levels, the EEG and a number of performance tests were recorded during spontaneous and oral contraceptive-controlled menstrual cycles. The mean alpha-frequency showed cyclic changes, i.e. slower alpha-waves during the follicular phase and faster alpha-waves during the luteal phase. Smaller cycle stage-dependent differences in the power of the theta- and beta-bands also were noted.An increase in several performance task scores was noted during the periovulatory period, whereas lowest performance scores were recorded during the late luteal and early menstrual phases. No such effects were observed in the same subjects while they were taking oral contraceptives.These results demonstrate that the gross electrical activity of the brain changes in a parallel with changed hormone levels. The changes in performance tests coincide with increasing or decreasing alpha activities in the EEG. The common underlying mechanism may be an activation of central nervous system monoaminergic pathways which are known to be involved in steroid feedback.     

Neurology of sex steroids and oral contraceptives

Under normal circumstances, sex steroids interact with diverse neural substrates to modulate a host of activities essential to the preservation of the individual and the species. In addition, sex hormones play an important role in various human neurologic conditions including strokes, migraine, certain movement disorders and peripheral neuropathies, and possibly even the behavior of CNS neoplasms.     

Inhibition of tissue-type plasminogen activator in plasma of women using oral contraceptives and in normal women during a menstrual cycle

Tissue-type plasminogen activator (t-PA) inhibition in plasma was assessed in 15 normal women and in 10 women using oral contraceptives (OC) containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. The levels of t-PA inhibition were significantly lower in the OC group with marked fluctuations related to the hormone cycle. Normal women had only minor fluctuations.     

Mood changes during the menstrual cycle and their relation to the use of oral contraceptive

The relation between the use of oral contraceptives and changes in positive and negative affect over the course of the menstrual cycle was studied in 50 women who completed a mood questionnaire daily during their menstrual cycle. Results indicated that users of oral contraceptives experience a higher level of positive affect during the cycle than do non-users. Positive affect scores were significantly higher than negative affect scores in the menstruation, follicular and luteal phases of the cycle. There were no significant differences between the groups and no discernible phasic changes on negative affect. Discussion of these findings centers on their implications concerning the relation between positive affect and oral contraceptives, the support they provide for the independence of positive and negative affect, and future directions for research in this area.     

Individual levels of plasma alpha 2-antiplasmin and alpha 2-macroglobulin during the normal menstrual cycle and in women on oral contraceptives low in oestrogen

Determinations of alpha 2-antiplasmin and alpha 2-macroglobulin were made in plasma samples collected during one normal or hormone induced cycle in 15 normal women and 11 women using oral contraceptives containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. The immediate plasmin inhibition test for determination of alpha 2-antiplasmin was modified for application on a centrifugal analyser using the chromogenic peptide substrate Chromozym PL. alpha 2-Macroglobulin concentration was determined by radial-immunodiffusion. There were no differences between the two groups in the mean concentrations of alpha 2-antiplasmin and alpha 2-macroglobulin, but during the cycle a slight, and statistically significant fall occurred in the alpha 2-antiplasmin concentration in both groups, while the fluctuations of alpha 2-macroglobulin were small and insignificant. Distinctly individual levels of both inhibitors were found to exist. The variations in these during the periods of the cycle fluctuated within a much narrower range than the variation of the total average. The results stress the importance of determining the fluctuations in individual levels in longitudinal studies. These findings exclude variations in the concentrations of these inhibitors as possible sources of a change in the antithrombotic potential caused by oral contraceptives.     

Plasminogen levels in healthy volunteers--influence of age, sex, smoking and oral contraceptives.

There is considerable doubt as to the importance of reduced plasminogen (PLG) activity as a risk factor for venous thrombosis. In the present study we have identified a wide range of PLG activities (25-200%) in a cohort of 9,611 blood donors. Males and females not taking hormonal contraceptives show a similar distribution of PLG, however, variation related to age appears to follow a different pattern in males and females. These differences are of doubtful clinical importance as are differences related to smoking. In contrast, females taking hormonal contraceptives or hormone replacement therapy (HRT) have up to 25% higher mean PLG levels in younger females but a less marked elevation (10%) is seen in 40-50 year olds. A PLG activity < 65% was recorded in 61 donors, none of whom appeared to have a history of thrombosis. These findings do not support the notion that reduced PLG is an important thrombophilic risk factor, however, further investigation of the donors with low PLG is required.     

Influence of male social contacts,exercise and all-female living conditions on the menstrual cycle

(1) The phenomenon of menstrual synchrony, i.e. a decrease in the time difference between onset dates of the menstrual flow among individuals, was demonstrated at a coeducational university. (2) The mean difference in onset dates of the menstrual flow for roommates and close friends became significantly shorter for the time period of October to March. (3) Casual exercise (swimming, tennis, and jogging) performed regularly was associated with significantly longer menstrual cycles. (4) Spending ‘social time’ with a male did not have any effect on the length of the menstrual cycle for the women in this study. (5) The findings confirm earlier reports of menstrual synchrony and extend them to an environment consisting of males and females.     

Ethanol and menstrual cycle interactions in the visual evoked response

Right and left hemisphere visual evoked responses from central locations were collected from 10 normal right-handed women in the follicular and luteal phases of their menstrual cycle. Subjects were tested sober and under 3 doses of ethanol. Amplitude and latency characteristics of the N120 and P180 components for each hemisphere were determined. Asymmetry between hemispheres for the various measurements was then calculated. The follicular phase was associated with a significant P180 latency asymmetry under baseline or placebo conditions. Virtually no asymmetry for P180 latency was present in the luteal phase. Ethanol eliminated the follicular P180 latency asymmetry and reduced the amplitude of both N120 and P180 in a dose-related fashion. The latency of the N120 component was prolonged by ethanol in a similar fashion. Interactions between menstrual cycle and ethanol occurred for both amplitude and latency of P180, but only for the response from the left hemisphere. These occurred at low or moderate doses of ethanol and illustrate the need to consider both the biphasic effects of low doses of ethanol and the possibility of lateralization of these effects to one cerebral hemisphere.     

Hormones, behaviour and the menstrual cycle

To date therefore, no consistent hormonal abnormality has been linked with premenstrual affective, physical or behavioural changes and, in turn, no consistent adverse behaviour has been positively linked with any particular menstrual cycle phase. At the same time, the proportion of actively menstruating women reported to identify premenstrual changes of a severity sufficient to warrant the illness label continues to fall so that a figure somewhere between 2 and 8% seems to be established where once figures in excess of 70% were claimed. The implication would seem to be that more thorough assessment of the relatively small number of women who are clearly identifiable as sufferers from cyclically-mediated symptoms might well cast light on possible hormonal-behavioural links where larger, less careful studies of heterogeneous samples of women have failed to do so. The great majority of women appear to negotiate the premenstrual phase of their menstrual cycles with little or no impairment or difficulty. A small number appear to be vulnerable and the possibility that it is, at least in part, a biological vulnerability is hinted at in those reports which tentatively suggest that some women who are especially prone to post-partum 'blues' and who are particularly sensitive to oral contraceptives may be especially prone to premenstrual tension. Finally, the ubiquity of premenstrually perceived 'changes' as distinct from 'symptoms' raises the possibility that the extent to which a woman experiences various premenstrual changes as complaint or illness may depend 'more on her basic personality and the circumstances in which she experiences the cyclical changes than on the underlying cyclical mechanism'.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones

Recent observations indicate that sex and level of steroid hormones may influence cortical networks associated with specific cognitive functions, in particular visuo-spatial abilities.

The present study probed the influence of sex, menstrual cycle, and sex steroid hormones on 3D mental rotation and brain function using 3-T fMRI. Twelve healthy women and 12 men were investigated. Menstrual cycle and hormone levels were assessed. The early follicular and midluteal phase of the menstrual cycle were chosen to examine short-term cyclical changes.

Parietal and frontal areas were activated during mental rotation in both sexes. Significant differences between men and women were revealed in both phases of menstrual cycle. In men we observed a significant correlation of activation levels with testosterone levels in the left parietal lobe (BA 40). In women, a cycle-dependent correlation pattern was observed for testosterone: brain activation correlated with this male hormone only during the early follicular phase. In both cycle phases females’ brain activation was significantly correlated with estradiol in frontal and parietal areas.

Our study provides evidence that fMRI-related activity during performance of cognitive tasks varies across sex and phases of the menstrual cycle. The variation might be partly explained by better task performance in men, but our results indicate that further explanations like basic neuronal or neurovascular effects modulated by steroid hormones must be considered. Both estradiol and testosterone levels may influence fMRI signals of cognitive tasks, which should affect selection of subjects for future fMRI studies.     

The impact of epilepsy surgery on sex hormones and the menstrual cycle in female patients.

We investigated the impact of temporal lobe epilepsy surgery on sex hormones and menstrual cycles. Sixteen female patients with temporal lobe epilepsy were investigated prior to surgery and 3, 6, and 12 months after surgery. The patients received carbamazepine (CBZ) as monotherapy (10 patients) or in combination with other antiepileptic drugs (six patients). Antiepileptic drugs were maintained after surgery. During the 1-year follow-up after surgery eight patients (50%) remained completely free of seizures. In another four patients (25%) only rare disabling seizures occurred. There were no significant differences between pre-surgical and post-surgical serum concentrations of testosterone, free testosterone, prolactin, dehydroepiandrosterone sulfate, growth hormone, cortisol and sex hormone binding globulin. There was, however, a significant increase in serum androstenedione concentration 6 months post-surgically (P < 0.02). Documentation of menstrual cycles in addition to laboratory parameters revealed individual post-surgical changes of the menstrual cycle in eight patients. Four patients had a change in menstrual periodicity: two patients with complete seizure control had regular cycles instead of oligomenorrhoea and two patients with incomplete seizure control had oligomenorrhoea instead of regular cycles. These data indicate that at least in some patients with temporal lobe epilepsy surgical treatment influences menstrual periodicity.     

The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones

This study examines the neurobiology of semantic retrieval and describes the influence of gender, menstrual cycle, and sex hormones on semantic networks. Healthy right-handed subjects (12 men, 12 women) were investigated with 3T-fMRI during synonym generation. Behavioral performance and sex hormone levels were assessed. Women were examined during the early follicular and midluteal cycle phase. The activation pattern in all groups involved left frontal and temporal as well as bilateral medial frontal, cingulate, occipital, basal ganglia, and cerebellar regions. Men showed greater left frontal activation than women in both menstrual cycle phases. Women yielded high correlations of left prefrontal activation with estradiol in the midluteal phase and with progesterone in both phases. Testosterone levels correlated highly with left prefrontal activation in all three groups. In all, we describe a cerebral network involved in semantic processing and demonstrate that it is significantly affected by gender and sex steroid hormones.